Problematic use of prescription opioid drugs: Classification and effective treatments

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Schematic representation of the symptomatic treatment of PCOS, which must be variable and personalised according to the needs of each patient. In all cases we will always recommend hygienic-dietetic measures designed to maintain a normal weight. OC provide the benefit of endometrial protection and improve symptoms of androgen excess. *When an antiandrogen is used, a safe method of contraception must be also used in all cases. †In the case of women who do not experience psycho-emotional impact from hyperandrogenism, are not sexually active or/and do not want contraception, cyclic progestogens will be the first therapeutic option. ‡To determine the ovulatory rhythm, the patient should first determine their basal temperature, rectally, as soon as they wake up and before getting out of bed (there will be an elevation of 0.3 to 0.5°C on the days immediately following ovulation); this should be carried out for at least three to four months to accurately estimate the patient's fertile days and schedule intercourse dates. If there is a certain regularity in ovulation, intercourse will be recommended on alternate days for at least one week, starting two or three days before the theoretical date of the ovulatory peak. OC: oral contraceptives; IUD: intrauterine device." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Andrés E. Ortiz-Flores, Manuel Luque-Ramírez, Héctor F. Escobar-Morreale" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Andrés E." "apellidos" => "Ortiz-Flores" ] 1 => array:2 [ "nombre" => "Manuel" "apellidos" => "Luque-Ramírez" ] 2 => array:2 [ "nombre" => "Héctor F." 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Between 2005 and 2015, its consumption in Spain increased by 253.59%.<a class="elsevierStyleCrossRefs" href="#bib0165">1,2</a> The greatest increase has been in the treatment of non-oncological chronic pain (with an estimated prevalence of 17% in the Spanish population<a class="elsevierStyleCrossRef" href="#bib0175">3</a>), which usually uses high doses and long-term treatments (more than 3–6 months), despite the lack of scientific evidence.<a class="elsevierStyleCrossRefs" href="#bib0180">4,5</a>An increase in the prescription of opioid analgesics worldwide has undoubtedly alleviated the suffering of many patients with chronic pain, but it has also been associated with a marked increase in problems related to its long-term use, although there are no reliable data on the real incidence.<a class="elsevierStyleCrossRef" href="#bib0190">6</a>Although underappreciated since the 1980s,<a class="elsevierStyleCrossRef" href="#bib0195">7</a> disorders emerging from the use of prescription opioids are a reality, not only in the United States. In the United States, where overdose mortality rates related to these drugs have tripled, associated emergencies have increased by 153% and the initiation of treatment by opioids other than heroin by 236%.<a class="elsevierStyleCrossRef" href="#bib0200">8</a> The problems related to these drugs are more common than we know, and this is also true of Spain. Furthermore, no patients with chronic pain are immune to addiction, although it occurs in a small percentage. While tolerance and withdrawal symptoms are expected, addiction is unpredictable, sets in slowly and becomes a chronic disease in itself, requiring specific treatment.<a class="elsevierStyleCrossRef" href="#bib0205">9</a>There is not yet enough scientific evidence on specific recommendations.Classification of problems related to prescription opioidsAccording to the classification of problems related to the use of prescription drugs by Smith et al.<a class="elsevierStyleCrossRef" href="#bib0210">10</a> (2013), and specifically in regard to opioid analgesics, we could define the following terms.Therapeutic errorThis refers to any error in the treatment regime, whether committed by the patient, the doctor, the pharmacist or any person responsible for its administration. This section includes errors in dosage, interactions with other drugs, accidentally taking a double dose, administering the drug by an incorrect route or offering it to someone other than the patient it has been prescribed to.TamperingCrushing the tablets to sniff them, heating the transdermal patches or chewing the sublingual fentanyl tablets to increase the effect are examples of an inappropriate tampering of opioid analgesic formulations.Incorrect useThis term refers to any intentionally inappropriate therapeutic use, not following prescription guidelines, regardless of whether or not the patient has presented adverse effects. It would include, for example, increasing the dose of the opioid without medical supervision to increase the analgesic effect and self-medication to treat symptoms other than those of pain, such as insomnia.Abstinence syndromeThese are a set of symptoms and signs that appear when the opioid analgesic blood concentration decreases (end of a dose interval, reduction of the dose, suppression of the opioid or administration of an antagonist drug). Symptoms usually appear 6–12h after the last dose of a short-acting opioid or 24–48h after the suppression of long-acting opioids.OverdoseThis term implies an excessive exposure to the drug resulting in acute intoxication, which in some cases can be fatal. This excessive exposure may have been cause by a clinical overdose (errors in the prescription, in the administration or in the dosage), accidentally (in case of abuse or addiction) or intentionally (suicidal intention).Aberrant behaviourAre all those behaviours associated with opioid analgesics that fall outside the limits of the established treatment regime agreed with the patient, suggesting the possible existence of an opioid use disorder. Some examples include:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Repeatedly using all prescribed medication in a short time.</li><li class="elsevierStyleListItem" id="lsti0010">-Requesting prescriptions from several doctors.</li><li class="elsevierStyleListItem" id="lsti0015">-Frequent loss of prescriptions.</li><li class="elsevierStyleListItem" id="lsti0020">-Frequently requesting dose increases.</li><li class="elsevierStyleListItem" id="lsti0025">-Increasing dosage without medical supervision.</li><li class="elsevierStyleListItem" id="lsti0030">-Accessing opioids outside the official drug circuit.</li><li class="elsevierStyleListItem" id="lsti0035">-Using different routes of administration, tampering with the forms of presentation (crushing and snorting the tablets, heating the patches, etc.).</li><li class="elsevierStyleListItem" id="lsti0040">-Often sedated or drowsy at consultations.</li><li class="elsevierStyleListItem" id="lsti0045">-Focusing exclusively on opioids during consultations.</li><li class="elsevierStyleListItem" id="lsti0050">-Frequent use of emergency services to request more medication.</li><li class="elsevierStyleListItem" id="lsti0055">-Rejecting treatments and/or non-pharmacological options that do not contain opioids.</li><li class="elsevierStyleListItem" id="lsti0060">-Deterioration of social relationships, social isolation. Concern transmitted by family members.</li></ul>Opioid use disorderThe latest edition of the Diagnostic and Statistical Manual of Mental Disorders,<a class="elsevierStyleCrossRef" href="#bib0215">11</a> includes the terms abuse and addiction under one unique term: opioid use disorders. In order to diagnose the patient as such, they must present a problematic pattern of consumption that causes a clinically significant impairment or discomfort and they must manifest at least two of the situations specified in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Tolerance and abstinence syndrome may be considered diagnostic criteria only in those patients being treated with opioids who do not maintain adequate medical supervision and who do not adhere to prescription guidelines.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Dependence vs. addictionThere is currently a tendency to not use the term physical dependence, since it is not comparable to addiction and they are often confused. The term physical dependence refers only to an adaptive physiological process in response to the drug, which is associated with withdrawal symptoms when the drug is stopped abruptly or after the administration of an antagonist. It also includes the phenomenon of tolerance, which implies the need to increase the dose of the opioid periodically to maintain the level of analgesia.It is thus no surprise that patients with pain who take continuous opioid analgesics are dependent on these drugs and that the abrupt interruption of treatment triggers a withdrawal syndrome. But this does not necessarily mean that they are addicted, in the same way that a diabetic patient is not considered to be addicted to insulin, although they are dependent on it. But it is important to point out that while the consumer of illegal opiates, in the early stages of addiction, compulsively seeks opiates to achieve pleasant effects (euphoria, wellbeing or highs as a positive reinforcement to continue consumption), patients with chronic pain treated with opioids usually skip this stage. In these patients, the tolerance that is not satisfied with an increase in the dose will manifest as withdrawal (anxiety, anhedonia, hyperalgesia). In vulnerable patients, the negative reinforcement involved in the disappearance of withdrawal symptoms after taking the opioid becomes the driving force behind a compulsive search.<a class="elsevierStyleCrossRef" href="#bib0220">12</a> Thus, tolerance and the symptomatology of abstinence become complex and difficult to manage. At this point, although diagnosis is not clear, a loss of control over the use of the drug is so similar to an addiction that it must be treated in a similar way to how classical addition is treated, despite the fact that these patients present a very different profile (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) to the consumer of illegal opiates.<a class="elsevierStyleCrossRef" href="#bib0225">13</a><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Prevention and treatment of overdoses by opioid analgesicsAcute intoxication symptoms may appear in patients treated with opioid analgesics, either due to clinical overdose (errors in dose adjustments, prescriptions, administration or in dosage prescribed), accidental overdose (in case of disorders due to the use of opioids) or intentional overdose.<a class="elsevierStyleCrossRef" href="#bib0190">6</a>Numerous studies indicate that the morbidity and mortality related to opioid overdoses is significantly reduced if patients, their relatives or even professionals at the service of the community (local police, civil protection) are informed and educated on how to prevent, recognise and respond to an overdose event, including training in the administration of naloxone.<a class="elsevierStyleCrossRefs" href="#bib0230">14–16</a> This could reverse a significant number of acute episodes, and the patient would subsequently be transferred to a hospital until complete stabilisation.Previously trained primary care teams have privileged knowledge and can offer this information and training to anyone who may experience or witness an opioid overdose episode, at least in those cases with clear risk factors (patients with a history of overdose, substance use disorder, morphine equivalent dose regimen of over 50mg or simultaneous use of benzodiazepines).<a class="elsevierStyleCrossRef" href="#bib0235">15</a> Moreover, this measure may make patients more aware of the risks associated with these drugs, thus improving the safety of the treatments.Importantly, treatments with opioid agonists (methadone or buprenorphine) reduce rates of subsequent morbidity and mortality in patients who survive a first overdose episode, even if only a minority of these patients are then included in maintenance programmes for these drugs.<a class="elsevierStyleCrossRef" href="#bib0245">17</a>Effective treatments of disorders by use of prescription opioidsThere are several treatment options that have proven efficacy in opioid use disorders; they all include pharmacological and non-pharmacological measures, such as behavioural therapies. Although a behavioural or pharmacological approach alone may be sufficient, there is ample evidence showing that the combined approach of both therapies is the best option.<a class="elsevierStyleCrossRefs" href="#bib0250">18–20</a> Psychosocial interventions should include programmes that are effective both in opioid addiction<a class="elsevierStyleCrossRef" href="#bib0265">21</a> and in the treatment of chronic pain.<a class="elsevierStyleCrossRef" href="#bib0270">22</a>In any case, treatment must always be personalised and comprehensive, and always consider the individual needs of each patient.Treatment based on abstinenceThis consists in the detoxification of the prescribed opioid (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>), followed by a drug-free detoxification programme that includes psychosocial interventions. It is considered the least effective intervention (higher risk of relapse and higher mortality), especially if psychosocial interventions are not included. It may be indicated for patients who choose this option themselves or those with a short history of opioid abuse, assessing the need for detoxification in a hospital setting.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>It is very important to reiterate to patients that their tolerance to opioids is lost after detoxification within one or two weeks, so if they consume opioids at the doses that were administered before detoxification, they have a high risk of overdosing.Structured treatment with opioidsThis treatment consists of continuing to administer opioids (not methadone or buprenorphine) under close supervision and under pre-established conditions agreed upon with the patient to minimise misuse. This programme must include at least: (a) signing a treatment contract; (b) frequent dispensing intervals for prescriptions (1–2 times per week); (c) frequent reviews (2–4 times per month); and d) patient education programmes. Considering the possibility of a family member or another responsible person controlling or administering the opioid medication would also be advisable, who could even to carry out periodic urine toxicological screening to detect the consumption of the prescribed opioid and other drugs.A patient who presents with a pain profile, in whom the use of opioids is clearly justified, does not have at that moment an alcohol or other drug addiction, and who shows one of the following characteristics is a candidate for a structured treatment with opioids:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0065">-Aberrant behaviours associated with opioids, provided that these are not highly indicative of addiction, such as accessing opioids outside the official circuit, requesting prescriptions from several doctors and tampering with the drug's presentation.</li><li class="elsevierStyleListItem" id="lsti0070">-High risk of developing an opioid use disorder (young patient, personal or family history of addiction to alcohol or other drugs, has anxiety or mood disorders), even if there are no aberrant behaviours.</li><li class="elsevierStyleListItem" id="lsti0075">-Treatment with immediate release transmucosal fentanyl formulations. In this regard, it is important to note that the Spanish Agency for Medicines and Health Products issued an informative note in February<a class="elsevierStyleCrossRef" href="#bib0275">23</a> recommending that professionals respect authorised conditions of use (according to its technical specifications, these formulations are only indicated for the treatment of breakthrough pain in cancer patients who are already on basic treatment with major opioids) “to minimise the risk of abuse and/or dependence”. They are very potent formulations, with quick action and short duration, and their use beyond 3–7 days is associated with a high risk of tolerance, dose escalation and addiction.<a class="elsevierStyleCrossRefs" href="#bib0190">6,24</a> The Spanish Agency for Medicines and Health Products recommends assessing the need for treatment and the use of other alternatives in patients with chronic non-cancer pain that are already undergoing treatment with these formulations.</li></ul>In these patients, a rotation to an opioid from a different group could be attempted, with morphine being the best option, as it is a powerful opioid, has the greatest experience of use and is the most cost-effective. In addition, none of the new opioids marketed have been shown to be more effective or safer than morphine.<a class="elsevierStyleCrossRef" href="#bib0190">6</a>But the best option for these patients is a slow and progressive withdrawal of the opioid until it is suppressed, while other pharmacological alternatives that do not contain opioids and non-pharmacological therapies for the treatment of pain can be sought. The speed and duration of the withdrawal period will be adjusted according to the patient's response, to minimise withdrawal symptoms. In general, the reduction will be slower in patients who have been on opioid treatment for a longer time, who are afraid of the withdrawal process, and/or who have cardiorespiratory diseases or opioid use disorder.A suitable guideline for the opioid withdrawal process is decreasing the dose by approximately 10% of the initial dose every one or two weeks, or 25% of the current dose every three or four weeks. After reaching one third of the initial dose, reduction should be slower (5mg or less every 2–4 weeks).Multidisciplinary programmes are recommended in cases where dose reduction is complicated, with a coordinated collaboration between a variety of professionals (PC team, physiotherapist, occupational therapist, pharmacist, pain specialist, psychologist, psychiatrist, etc.).If this structured treatment fails, a priority referral to an addiction service is indicated, where methadone or buprenorphine/naloxone treatment will be assessed. There is a group of professionals who believe that primary care physicians or other prescribing specialists should be adequately trained to address these issues given that the problems related to opioid analgesics are becoming more frequent.<a class="elsevierStyleCrossRef" href="#bib0285">25</a> Additionally, we must not forget the importance of psychosocial interventions in these patients and the current lack in Spain of specialist professionals in this area within primary care teams, which makes comprehensive treatment difficult.Assisted treatment with medicationMedication-assisted treatment comprises the prescription of controlled amounts of long-acting opioid drugs within a comprehensive treatment programme that includes psychosocial interventions from the beginning. Spain has traditionally used three opioid drugs for this type of treatment: (a) naltrexone (antagonist), (b) methadone (pure agonist) and (c) buprenorphine/naloxone (partial agonist). The efficacy of agonist treatments (methadone and buprenorphine/naloxone) has been clearly demonstrated, while the evidence for naltrexone treatments is poor.<a class="elsevierStyleCrossRef" href="#bib0290">26</a>Although methadone has a greater experience of use and seems to show better retention rates in treatment, buprenorphine/naloxone has a more favourable safety profile and is a safe, effective and profitable option<a class="elsevierStyleCrossRef" href="#bib0295">27</a>; however, the fact that it is only partially financed by the national health system may limit its use in patients with a more depressed socioeconomic status. The priority for patients who are at high risk of abandoning treatment is retention, and as such they will most probably benefit more from a methadone maintenance programme. However, for patients with a high risk of toxicity, safety is the first consideration and as such they are clearly candidates for buprenorphine–naloxone replacement therapy.<a class="elsevierStyleCrossRef" href="#bib0300">28</a>In general, patients treated with buprenorphine/naloxone report several advantages over methadone, such as a ‘clearer state of mind’, less concentration difficulties, less social stigma, less drowsiness, greater decrease in desire for consumption and a simpler withdrawal when the end of substitution treatment is decided.<a class="elsevierStyleCrossRef" href="#bib0305">29</a> In short, the choice of methadone or buprenorphine/naloxone will depend on severity; concomitant medication; social context<a class="elsevierStyleCrossRef" href="#bib0300">28</a>; individual pharmacological and clinical parameters (efficacy, safety, pharmacological interactions, quality of life, medical or psychiatric comorbidities); patient's preferences (abstinence and recovery, or harm reduction) and the prescribing physician.Although there is not much or at most a moderate amount of evidence supporting the effectiveness of these treatments in patients with prescription opioid disorder,<a class="elsevierStyleCrossRef" href="#bib0310">30</a> most of the current guidelines recommend them as the most favourable option,<a class="elsevierStyleCrossRefs" href="#bib0190">6,31,32</a> obtaining better results with long-term treatments.While other professionals are not adequately trained, the conversion of the dose of any opioid to methadone or buprenorphine/naloxone equivalents should only be carried out by professionals who are experts in the treatment of these drugs, such that these treatments, for the time being, should be carried out only in specialised addiction services.In the same way as with heroin, there is no reliable equianalgesic table that allows us to calculate the exact dose of methadone or buprenorphine/naloxone equivalent to a given dose of any opioid analgesic. The most prudent course is to start treatment with a low dose of the substitute drug and adjust it according to clinical criteria, the patient's well-being and the need for a rescue dose. The majority of patients benefit from the dosage of the substitute divided into two or three doses per day.Methadone. Methadone is a synthetic opioid agonist that eliminates the symptoms of withdrawal syndrome and decreases the compulsive desire to consume other opioids.In patients with opioid use disorder analgesics should always start with low doses (15–20mg/day, divided into two or three daily doses). The patient will be evaluated every 24–48h, adjusting the methadone dose upwards (never increasing more than 30–50% of the initial dose) or downwards, according to clinical criteria and the patient's response, while simultaneously reducing the daily dose of the opioid being abused by 30–50%, withdrawing it in 3–4 days. Until a stable dose of methadone is reached, using non-opioid analgesics for the treatment of pain is appropriate.In most cases, the administration of methadone may be performed on an outpatient basis. If a hospital admission was required, depending on the profile of each patient, it would ideally be:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080">a.In the Pain Unit (if beds are available) or in the Internal Medicine Service. For patients who do not have adequate social support or are afraid of the change, withdrawal or pain syndromes; a psychiatric comorbidity (including a history or active consumption of alcohol or other drugs), or a medical comorbidity, or who do, but they are stabilised and not serious, when decompensation is not foreseeable.</li><li class="elsevierStyleListItem" id="lsti0085">b.Hospital admission to the Mental Health Service (short hospitalisation unit). For patients without significant medical comorbidity; with a history of psychiatric comorbidity (including a history or active consumption of alcohol or other drugs), or a current mental illness that has not been stabilised or is at risk of destabilisation.</li><li class="elsevierStyleListItem" id="lsti0090">c.Hospital admission into intensive care. For elderly patients; patients with significant decompensated medical comorbidity or those at risk of decompensation, or for those who have an intrathecal morphine pump.</li></ul>In all cases, a treatment contract should be signed that contains information on the treatment to be carried out and the general and specific rules for each service. Patient monitoring and treatment should be carried out by the specialists of each service, in close coordination and collaboration with specialists from the Pain Unit and the Addiction Service, who should be available for any required consultation or action.Patient monitoring and treatment is the responsibility of the addiction service specialist, with the collaboration of professionals from the other services.Buprenorphine/naloxone. Buprenorphine is a partial opioid agonist, with agonist or antagonist properties depending on the presence or absence of other opioids in the body. For this reason, waiting some time after the last dose of the opioid that is being abused is necessary, so as not to precipitate withdrawal syndrome. Induction should not be started until mild/moderate signs and symptoms are observed, which can be evaluated with the Clinical Opiate Withdrawal Scale, <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, where a score of ≥8 is considered to be confirmation. In general, we can prevent the precipitation of the withdrawal syndrome if we wait for the following times from the last dose of the opioid that is being abused:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0095">-Heroin and ultrafast release opioids: 6–12h.</li><li class="elsevierStyleListItem" id="lsti0100">-Immediate release opioids: 12–24h.</li><li class="elsevierStyleListItem" id="lsti0105">-Methadone and prolonged-release opioids: 36–48h.</li><li class="elsevierStyleListItem" id="lsti0110">-Transdermal patches: 48–72h.</li></ul><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Buprenorphine/naloxone tablets (2/0.5mg and 8/2mg), administered sublingually. Naloxone does not produce any clinical effect when administered this way; it only has an antagonistic effect when administered intravenously; it is present in tablet form to discourage its injection.Administration is carried out in the same way as it is for heroin users and is equally effective. The purpose is to administer the minimum dose to ensure the patient does not present withdrawal symptoms, but does achieve adequate opioid block.As a prior period without opioids is required (moderate withdrawal), in some cases these patients will need to be hospitalised, in order to properly control withdrawal symptoms. Outpatient administration may be attempted in patients who have a strong social support network, are highly motivated, are predisposed to the process and have an adequate understanding of the treatment and possible withdrawal symptoms that may appear. The criteria for the induction of buprenorphine–naloxone in a hospital setting will be the same as those indicated in the methadone summary.ConclusionPatients with chronic pain treated with opioid analgesics (both chronic, non-cancer pain and cancer pain associated with high survival rates in the medium/long term) are complex and pose a challenge for medicine. The situation can be complicated when long-term treatments with opioid analgesics are used at high doses, since it increases the risk of serious adverse effects related to these drugs. In clinical trials compared to placebo, opioid analgesics show an absolute rate of adverse effects of 78%, with 7.5% of these being severe effects.<a class="elsevierStyleCrossRef" href="#bib0180">4</a> However, there is no reliable information on addiction or other expected adverse effects from the continued use of opioids (alterations in mood, sleep apnoea, sexual dysfunction or hypogonadism). Some of these adverse effects appear after a latency period and most of the studies do not follow the patients beyond six months. This is a significant limitation to the evidence needed, which means that carrying out systematic studies with long-term follow-ups is essential in order to obtain more reliable data on the prevalence of all the adverse effects related to these drugs.There is currently no consensus on how to treat patients with chronic non-cancer pain who develop a disorder to using prescription opioids. Establishing personalised and multidisciplinary strategies, with the collaboration and coordination of all health-care areas is recommended. For the time being, assisted treatments with opioid agonists seem to be the most favourable option.Finally, we would like to highlight that the best treatment for disorders of opioid analgesics use is prevention, through the application of strategies that can minimise the risks associated with the misuse of these drugs while maximising their effectiveness. <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows some recommendations for the safe prescription of opioids.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Classification of problems related to prescription opioids" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Therapeutic error" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Tampering" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Incorrect use" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Abstinence syndrome" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Overdose" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Aberrant behaviour" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Opioid use disorder" ] ] ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Dependence vs. addiction" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Prevention and treatment of overdoses by opioid analgesics" ] 3 => array:3 [ "identificador" => "sec0055" "titulo" => "Effective treatments of disorders by use of prescription opioids" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Treatment based on abstinence" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Structured treatment with opioids" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Assisted treatment with medication" ] ] ] 4 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusion" ] 5 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-09-10" "fechaAceptado" => "2018-10-16" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Henche Ruiz AI. Uso problemático de los analgésicos opioides de prescripción: clasificación y tratamientos eficaces. Med Clin (Barc). 2019;152:458–465." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0910" ] ] ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Frequent consumption of higher amounts or for longer than expected \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Persistent desire or unsuccessful efforts to cut down or control opioid use. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Great deal of time spent on activities associated with its consumption (obtaining, using or recover from the opioid's effects) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Craving or a strong desire to use opioids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Recurrent opioid use resulting in a failure to fulfil major role obligations at work, school, or home \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. Continued opioid use, despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7. Important social, occupational, or recreational activities are given up or reduced because of opioid use \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8. Recurrent opioid use in situations in which it is physically hazardous \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9. Continued opioid use, despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10. Tolerance<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11. Withdrawal syndrome<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047644.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "This criterion is not considered to be met by those individuals who only take opioids under proper medical supervision." ] ] ] "descripcion" => array:1 [ "en" => "Criteria for diagnosis of opioid use disorder (DSM-5)." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Median age (45–65) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- No personal history of alcohol or other drug use \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Chronic pain that is difficult to treat, with a long history of ineffective treatments (‘revolving door’ patients) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Significant functional deterioration, with substantial limitations to quality of life \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Intense psychosocial stress and marked emotional component of pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- High rates of psychiatric comorbidity (depressive disorders, anxiety disorders, disorders related to traumas and stress factors, personality disorders) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Prolonged treatment with high doses of one or more opioids, one of them frequently being transmucosal fentanyl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Compulsive need to take prescribed opioids, even when they do not relieve pain, without being able to clearly determine the reasons, among which are the memory of untreated pain, pain relief, withdrawal symptoms or psychological discomfort \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047641.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Profile of patients with problematic use of opioid analgesics." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BDZ: benzodiazepines; ICU: intensive care unit." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comments \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A-2-adrenergic agonists \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clonidine (oral tablets of 0.150mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 1: 1–2 tablets every 8h, adjusting the dose according to abstinence symptoms. Maximum: 1mgDays 2–4: 2–3 tablets every 8h, adjusting the dose according to abstinence symptoms. Maximum: 1.3mgFrom day 5: reduce to 1 tablet per day until suspension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">They reduce abdominal pain, chills, muscle cramps, irritability and restlessness.They do not act on anxiety or insomnia.They require monitoring of the cardiovascular constants, since they can produce bradycardia and intense arterial hypotension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tizanidine (oral tablets of 2 and 4mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–4mg per day.When abstinence is controlled, reduce to 1 tablet per day until suspension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sedative neuroleptics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">QuetiapineOlanzapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–200mg/day5–10mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">They reduce agitation and anxiety. Atypical neuroleptics are recommended. Once the profile has been stabilised, a progressive reduction of the dose is carried out until suspension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Long-acting myorelaxing anxiolytics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DiazepamClonazepamDipotassium chloracepateKetazolam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–25mg/8h1–2mg/8h25–50mg/8h15–30mg/12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">They reduce the anxiety and agitation that accompany abstinence symptoms. After achieving stabilisation (3–4 days), progressively decrease the dose until suspension. Ten days of treatment usually suffice. Prolonging treatment beyond two months is not recommended due to the high risk of abuse or addiction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiepileptics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GabapentinaPregabalin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">300–800mg/8h150–300mg/12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Useful for stabilising patients’ mood and controlling pain with neuropathic characteristics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sedative antidepressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TrazodioneMirtazapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–100mg in the evening15–45mg in the evening \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Improve patients’ sleep patterns, without the high risk of abusing BZDs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-opioid analgesics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antipyretic analgesics (paracetamol, metamizole) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At usual doses, they reduce the musculoskeletal pain and fever associated with the withdrawal syndrome. Classical NSAIDs present a higher gastrointestinal risk, while COXIB present higher cardiovascular risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-steroidal anti-inflammatory drugs (NSAIDs):Classical NSAIDs (ibuprofen, ibuprofen–arginine, naproxen, ketorolac, dexketoprofen, diclofenac) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">COX-2 (celecoxib, etoricoxib) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiemetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metoclopramide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10mg/8h (oral) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Domperidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–20mg/8h (oral) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ondansetron \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4–8mg/12h (oral) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antidiarrheals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mebevirin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">135mg/8h, 20min before the main meal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Loperamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2mg after each bowel movement (maximum: 16mg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Racecadotril \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100mg/8h, before the main meals. For a maximum of 7 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Powerful sedatives \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PropofolMidazolam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In bolus or perfusion.They require close monitoring of the patient; administration should only be carried out by professionals who are experts in the treatment of these drugs, such that their use will be limited to detoxification in the ICU. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047636.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Most commonly used drugs for opioid detoxification." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted and translated from Wesson D.R. and Ling W.’s The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003; 35:253–9." "tablatextoimagen" => array:12 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resting pulse rate _____________ beats/minute \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(measure after the patient has been sitting or lying down for one minute) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Pulse rate of 80 or below \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Pulse rate of 81–100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Pulse rate of 101–120 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Pulse rate greater than 120 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047646.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sweating (during the last 30 minutes; not due to room temperature or patient activity) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 No report of chills or flashing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Subjective report of chills or flashing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Flushed or observable moistness on face \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 Beads of sweat on brow or face \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Sweat streaming off face \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047647.png" ] ] 2 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Restlessness (observation during assessment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Able to remain sit still \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Reports difficulty sitting still, but is able to do so \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 Frequent shifting or extraneous movements of legs/arms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 Unable to sit still for more than a few seconds \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047639.png" ] ] 3 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pupil size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Pupils pinned or normal size for room light \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Pupils possibly larger than normal for room light \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Pupils moderately dilated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 Pupils so dilated that only the rim of the iris is visible \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047643.png" ] ] 4 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bone or articular pain (if patient was previously suffering from pain, only the additional component attributed to opiates withdrawal is scored) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Absence of pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Mild, diffuse discomfort \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Patient reports severe diffuse aching of articulations/muscles \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Patient rubs articulations or muscles and is unable to sit still because of discomfort \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047637.png" ] ] 5 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rhinorrhea (runny nose) or tearing (not accounted for by cold/flu symptoms or allergies) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Not present \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Nasal congestion or unusually moist eyes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Rhinorrhea or obvious tearing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Constant rhinorrhea or tears streaming down cheeks \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047649.png" ] ] 6 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Digestive discomfort (during the last 30 min) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Absence of digestive symptoms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Stomach cramps \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Nausea or loose stools \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 Vomiting or diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 Multiple episodes of diarrhoea or vomiting \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047650.png" ] ] 7 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tremors (observation of outstretched hands) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 No tremor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Tremor can be felt, but not observed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Slight tremor observable \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Considerable trembling or muscle contractions/twitching \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047642.png" ] ] 8 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yawning (observation during assessment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 No yawning \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Yawning once or twice during assessment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 Yawning three or more times during assessment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 Yawning several times/minute \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047648.png" ] ] 9 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anxiety or irritability \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 No anxiety or irritability \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 Patient reports increasing irritability or anxiousness \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 The patient is obviously irritable or anxious \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 The patient is so irritable or anxious that participation in the assessment is difficult \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047635.png" ] ] 10 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Piloerection (goose flesh skin) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 Soft skin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 Piloerrection of skin can be felt or hairs standing up on arms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 Prominent piloerection \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047640.png" ] ] 11 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total score (sum of the 11 items) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild: 5–12; Moderate: 13–24; Moderately severe: 25–36; Severe withdrawal: ≥36. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047638.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical Opiate Withdrawal Scale (COWS)." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Pain management must always be personalised, with a comprehensive, multidisciplinary and structured approach from the beginning of treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. A complete clinical evaluation should be carried out that includes not only an assessment of pain, but also of the patients’ functional status, quality of life and potential risk of overdose and opioid abuse. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. The patient should be clearly and completely informed about the treatment (benefits and possible risks, including addiction and overdose) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Always following the WHO analgesic ladder, to ensure a progressive approach is advisable. Opioid analgesics are not first-line drugs in the treatment of chronic, nociceptive or neuropathic pain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Although no absolute contraindications have been established for the use of opioids for the treatment of chronic pain, there is evidence that in some cases its use is not recommended (e.g. primary headache, fibromyalgia, current or past substance use disorder, major depressive disorder and/or suicidal tendencies, irritable bowel syndrome, etc.) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. In general, treatment with opioid analgesics should only be considered in those cases of moderate/intense nociceptive pain, when these two circumstances occur: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous failure of all possible non-opioid treatments, including minimally invasive techniques \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Expectations of short-term resolution of the main origin of pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7. Only a small proportion of patients with chronic non-cancer pain will benefit from opioid treatment, and their effectiveness is not clearly established over 6–12 months. Accepting that opioid treatment may fail is the first step in improving its use \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8. The more chronic and complex the pain and the younger the patient, the less indicated opioids are \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9. In patients with a history of drug abuse, psychiatric illness or misuse of medications, treatment with opioids should only be considered if close control can be guaranteed. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10. Long-term treatment, especially at high doses, increases the risk of overdose and addiction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11. The concomitant use of benzodiazepines, alcohol or other central nervous system depressants, together with opioids, increases the risk of overdose, so they should be avoided \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12. One must always bear in mind, from the beginning of treatment, the emotional component of chronic pain, which must also be appropriately treated. If we do not address that issue, we run the risk of perpetuating the pain and disability \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13. Dose adjustment will be made with immediate release formulations (lower risk of overdose). Once the minimum effective dose is reached, the patient can be transferred to prolonged-release formulations (lower risk of addiction) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14. There is no evidence of greater analgesic efficacy of any opioid compared to the rest. The powerful opioid analgesic of choice continues to be morphine, due to its greater experience of use and because it is the most cost-effective \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15. Transmucosal fentanyl formulations in adequate doses are only indicated for breakthrough pain in cancer patients who are already undergoing treatment with another opioid \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16. Reanalysis must be carried out periodically (max. every 3 months, but more often for patients whose morphine equivalent dose (MED) is more than 50mg) for: pain, function, quality of life, risk of overdose or misuse, presence of psychiatric comorbidity, compliance with non-opioid treatments prescribed, etc. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17. In patients whose MED is 90mg for more than 6 months, trying to reduce the dose to verify that the analgesic effect is maintained is indicated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18. If an opioid at moderate doses does not work, rotation to another opioid from a different group is indicated. The following is NOT indicated: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increasing doses to unacceptable levels \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The addition of another opioid by the same or a different administration route (including transmucosal fentanyl) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19. All patients requiring MED higher than 120mg who have uncontrolled pain should be categorised as differential diagnosis of opioid-induced hyperalgesia, opioid use disorder or treatment failure, and should be referred to the Reference Pain Unit \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20. The slow and progressive reduction of opioid treatment until suppression, if possible, will be indicated in the following cases: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The patient has requested it \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resolution of the cause that caused the pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absence of clinically significant improvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MED of ≥50mg per day are being administered without a clear benefit \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concomitant use of benzodiazepines or alcohol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Signs of a disorder of other substances \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Founded suspicion or certainty of problems related to the use of opioid analgesics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">If in all these cases complete withdrawal of the opioid is not possible, initiating treatment with agonists (methadone or buprenorphine/naloxone) is recommended. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047645.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommendations for the safe prescription of opioids in chronic pain." ] ] 5 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 357817 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0165" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilización de opioides en España (1992-2006)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "AEMPS – Agencia Española de Medicamentos y Productos Sanitarios" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2009" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0170" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilización de medicamentos opioides en España durante el periodo 2008-2015" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "AEMPS – Agencia Española de Medicamentos y Productos Sanitarios" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2017" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0175" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Situación actual del dolor crónico en España: iniciativa “Pain Proposal”" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. 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Problematic use of prescription opioid drugs: Classification and effective treatments

Uso problemático de los analgésicos opioides de prescripción: clasificación y tratamientos eficaces

Ana Isabel Henche Ruiz

Unidad de Conductas Adictivas, Servicio de Psiquiatría, Complejo Hospitalario de Toledo, SESCAM, Toledo, Spain

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    "titulo" => "Problematic use of prescription opioid drugs&#58; Classification and effective treatments"
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        "titulo" => "Uso problem&#225;tico de los analg&#233;sicos opioides de prescripci&#243;n&#58; clasificaci&#243;n y tratamientos eficaces"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the last twenty years&#44; opioid analgesics have become the cornerstone of pain management&#46; Between 2005 and 2015&#44; its consumption in Spain increased by 253&#46;59&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">1&#44;2</span></a> The greatest increase has been in the treatment of non-oncological chronic pain &#40;with an estimated prevalence of 17&#37; in the Spanish population<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a>&#41;&#44; which usually uses high doses and long-term treatments &#40;more than 3&#8211;6 months&#41;&#44; despite the lack of scientific evidence&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">An increase in the prescription of opioid analgesics worldwide has undoubtedly alleviated the suffering of many patients with chronic pain&#44; but it has also been associated with a marked increase in problems related to its long-term use&#44; although there are no reliable data on the real incidence&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although underappreciated since the 1980s&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> disorders emerging from the use of prescription opioids are a reality&#44; not only in the United States&#46; In the United States&#44; where overdose mortality rates related to these drugs have tripled&#44; associated emergencies have increased by 153&#37; and the initiation of treatment by opioids other than heroin by 236&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> The problems related to these drugs are more common than we know&#44; and this is also true of Spain&#46; Furthermore&#44; no patients with chronic pain are immune to addiction&#44; although it occurs in a small percentage&#46; While tolerance and withdrawal symptoms are expected&#44; addiction is unpredictable&#44; sets in slowly and becomes a chronic disease in itself&#44; requiring specific treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There is not yet enough scientific evidence on specific recommendations&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Classification of problems related to prescription opioids</span><p id="par0025" class="elsevierStylePara elsevierViewall">According to the classification of problems related to the use of prescription drugs by Smith et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> &#40;2013&#41;&#44; and specifically in regard to opioid analgesics&#44; we could define the following terms&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Therapeutic error</span><p id="par0030" class="elsevierStylePara elsevierViewall">This refers to any error in the treatment regime&#44; whether committed by the patient&#44; the doctor&#44; the pharmacist or any person responsible for its administration&#46; This section includes errors in dosage&#44; interactions with other drugs&#44; accidentally taking a double dose&#44; administering the drug by an incorrect route or offering it to someone other than the patient it has been prescribed to&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Tampering</span><p id="par0035" class="elsevierStylePara elsevierViewall">Crushing the tablets to sniff them&#44; heating the transdermal patches or chewing the sublingual fentanyl tablets to increase the effect are examples of an inappropriate tampering of opioid analgesic formulations&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Incorrect use</span><p id="par0040" class="elsevierStylePara elsevierViewall">This term refers to any intentionally inappropriate therapeutic use&#44; not following prescription guidelines&#44; regardless of whether or not the patient has presented adverse effects&#46; It would include&#44; for example&#44; increasing the dose of the opioid without medical supervision to increase the analgesic effect and self-medication to treat symptoms other than those of pain&#44; such as insomnia&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Abstinence syndrome</span><p id="par0045" class="elsevierStylePara elsevierViewall">These are a set of symptoms and signs that appear when the opioid analgesic blood concentration decreases &#40;end of a dose interval&#44; reduction of the dose&#44; suppression of the opioid or administration of an antagonist drug&#41;&#46; Symptoms usually appear 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h after the last dose of a short-acting opioid or 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h after the suppression of long-acting opioids&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Overdose</span><p id="par0050" class="elsevierStylePara elsevierViewall">This term implies an excessive exposure to the drug resulting in acute intoxication&#44; which in some cases can be fatal&#46; This excessive exposure may have been cause by a clinical overdose &#40;errors in the prescription&#44; in the administration or in the dosage&#41;&#44; accidentally &#40;in case of abuse or addiction&#41; or intentionally &#40;suicidal intention&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Aberrant behaviour</span><p id="par0055" class="elsevierStylePara elsevierViewall">Are all those behaviours associated with opioid analgesics that fall outside the limits of the established treatment regime agreed with the patient&#44; suggesting the possible existence of an opioid use disorder&#46; Some examples include&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Repeatedly using all prescribed medication in a short time&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Requesting prescriptions from several doctors&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Frequent loss of prescriptions&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Frequently requesting dose increases&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Increasing dosage without medical supervision&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Accessing opioids outside the official drug circuit&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">Using different routes of administration&#44; tampering with the forms of presentation &#40;crushing and snorting the tablets&#44; heating the patches&#44; etc&#46;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Often sedated or drowsy at consultations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Focusing exclusively on opioids during consultations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Frequent use of emergency services to request more medication&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">Rejecting treatments and&#47;or non-pharmacological options that do not contain opioids&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Deterioration of social relationships&#44; social isolation&#46; Concern transmitted by family members&#46;</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Opioid use disorder</span><p id="par0120" class="elsevierStylePara elsevierViewall">The latest edition of the Diagnostic and Statistical Manual of Mental Disorders&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> includes the terms abuse and addiction under one unique term&#58; <span class="elsevierStyleItalic">opioid use disorders</span>&#46; In order to diagnose the patient as such&#44; they must present a problematic pattern of consumption that causes a clinically significant impairment or discomfort and they must manifest at least two of the situations specified in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Tolerance and abstinence syndrome may be considered diagnostic criteria only in those patients being treated with opioids who do not maintain adequate medical supervision and who do not adhere to prescription guidelines&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Dependence vs&#46; addiction</span><p id="par0125" class="elsevierStylePara elsevierViewall">There is currently a tendency to not use the term <span class="elsevierStyleItalic">physical dependence</span>&#44; since it is not comparable to addiction and they are often confused&#46; The term physical dependence refers only to an adaptive physiological process in response to the drug&#44; which is associated with withdrawal symptoms when the drug is stopped abruptly or after the administration of an antagonist&#46; It also includes the phenomenon of <span class="elsevierStyleItalic">tolerance</span>&#44; which implies the need to increase the dose of the opioid periodically to maintain the level of analgesia&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">It is thus no surprise that patients with pain who take continuous opioid analgesics are dependent on these drugs and that the abrupt interruption of treatment triggers a withdrawal syndrome&#46; But this does not necessarily mean that they are addicted&#44; in the same way that a diabetic patient is not considered to be addicted to insulin&#44; although they are dependent on it&#46; But it is important to point out that while the consumer of illegal opiates&#44; in the early stages of addiction&#44; compulsively seeks opiates to achieve pleasant effects &#40;euphoria&#44; wellbeing or highs as a positive reinforcement to continue consumption&#41;&#44; patients with chronic pain treated with opioids usually skip this stage&#46; In these patients&#44; the tolerance that is not satisfied with an increase in the dose will manifest as withdrawal &#40;anxiety&#44; anhedonia&#44; hyperalgesia&#41;&#46; In vulnerable patients&#44; the negative reinforcement involved in the disappearance of withdrawal symptoms after taking the opioid becomes the driving force behind a compulsive search&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">12</span></a> Thus&#44; tolerance and the symptomatology of abstinence become complex and difficult to manage&#46; At this point&#44; although diagnosis is not clear&#44; a loss of control over the use of the drug is so similar to an addiction that it must be treated in a similar way to how classical addition is treated&#44; despite the fact that these patients present a very different profile &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; to the consumer of illegal opiates&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Prevention and treatment of overdoses by opioid analgesics</span><p id="par0135" class="elsevierStylePara elsevierViewall">Acute intoxication symptoms may appear in patients treated with opioid analgesics&#44; either due to clinical overdose &#40;errors in dose adjustments&#44; prescriptions&#44; administration or in dosage prescribed&#41;&#44; accidental overdose &#40;in case of disorders due to the use of opioids&#41; or intentional overdose&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Numerous studies indicate that the morbidity and mortality related to opioid overdoses is significantly reduced if patients&#44; their relatives or even professionals at the service of the community &#40;local police&#44; civil protection&#41; are informed and educated on how to prevent&#44; recognise and respond to an overdose event&#44; including training in the administration of naloxone&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">14&#8211;16</span></a> This could reverse a significant number of acute episodes&#44; and the patient would subsequently be transferred to a hospital until complete stabilisation&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Previously trained primary care teams have privileged knowledge and can offer this information and training to anyone who may experience or witness an opioid overdose episode&#44; at least in those cases with clear risk factors &#40;patients with a history of overdose&#44; substance use disorder&#44; morphine equivalent dose regimen of over 50<span class="elsevierStyleHsp" style=""></span>mg or simultaneous use of benzodiazepines&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> Moreover&#44; this measure may make patients more aware of the risks associated with these drugs&#44; thus improving the safety of the treatments&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Importantly&#44; treatments with opioid agonists &#40;methadone or buprenorphine&#41; reduce rates of subsequent morbidity and mortality in patients who survive a first overdose episode&#44; even if only a minority of these patients are then included in maintenance programmes for these drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Effective treatments of disorders by use of prescription opioids</span><p id="par0155" class="elsevierStylePara elsevierViewall">There are several treatment options that have proven efficacy in opioid use disorders&#59; they all include pharmacological and non-pharmacological measures&#44; such as behavioural therapies&#46; Although a behavioural or pharmacological approach alone may be sufficient&#44; there is ample evidence showing that the combined approach of both therapies is the best option&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">18&#8211;20</span></a> Psychosocial interventions should include programmes that are effective both in opioid addiction<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> and in the treatment of chronic pain&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">In any case&#44; treatment must always be personalised and comprehensive&#44; and always consider the individual needs of each patient&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Treatment based on abstinence</span><p id="par0165" class="elsevierStylePara elsevierViewall">This consists in the detoxification of the prescribed opioid &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; followed by a drug-free detoxification programme that includes psychosocial interventions&#46; It is considered the least effective intervention &#40;higher risk of relapse and higher mortality&#41;&#44; especially if psychosocial interventions are not included&#46; It may be indicated for patients who choose this option themselves or those with a short history of opioid abuse&#44; assessing the need for detoxification in a hospital setting&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">It is very important to reiterate to patients that their tolerance to opioids is lost after detoxification within one or two weeks&#44; so if they consume opioids at the doses that were administered before detoxification&#44; they have a high risk of overdosing&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Structured treatment with opioids</span><p id="par0175" class="elsevierStylePara elsevierViewall">This treatment consists of continuing to administer opioids &#40;not methadone or buprenorphine&#41; under close supervision and under pre-established conditions agreed upon with the patient to minimise misuse&#46; This programme must include at least&#58; &#40;a&#41; signing a treatment contract&#59; &#40;b&#41; frequent dispensing intervals for prescriptions &#40;1&#8211;2 times per week&#41;&#59; &#40;c&#41; frequent reviews &#40;2&#8211;4 times per month&#41;&#59; and d&#41; patient education programmes&#46; Considering the possibility of a family member or another responsible person controlling or administering the opioid medication would also be advisable&#44; who could even to carry out periodic urine toxicological screening to detect the consumption of the prescribed opioid and other drugs&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">A patient who presents with a pain profile&#44; in whom the use of opioids is clearly justified&#44; does not have at that moment an alcohol or other drug addiction&#44; and who shows one of the following characteristics is a candidate for a structured treatment with opioids&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">Aberrant behaviours associated with opioids&#44; provided that these are not highly indicative of addiction&#44; such as accessing opioids outside the official circuit&#44; requesting prescriptions from several doctors and tampering with the drug&#39;s presentation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">High risk of developing an opioid use disorder &#40;young patient&#44; personal or family history of addiction to alcohol or other drugs&#44; has anxiety or mood disorders&#41;&#44; even if there are no aberrant behaviours&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">Treatment with immediate release transmucosal fentanyl formulations&#46; In this regard&#44; it is important to note that the Spanish Agency for Medicines and Health Products issued an informative note in February<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a> recommending that professionals respect authorised conditions of use &#40;according to its technical specifications&#44; these formulations are only indicated for the treatment of breakthrough pain in cancer patients who are already on basic treatment with major opioids&#41; &#8220;to minimise the risk of abuse and&#47;or dependence&#8221;&#46; They are very potent formulations&#44; with quick action and short duration&#44; and their use beyond 3&#8211;7 days is associated with a high risk of tolerance&#44; dose escalation and addiction&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">6&#44;24</span></a> The Spanish Agency for Medicines and Health Products recommends assessing the need for treatment and the use of other alternatives in patients with chronic non-cancer pain that are already undergoing treatment with these formulations&#46;</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">In these patients&#44; a rotation to an opioid from a different group could be attempted&#44; with morphine being the best option&#44; as it is a powerful opioid&#44; has the greatest experience of use and is the most cost-effective&#46; In addition&#44; none of the new opioids marketed have been shown to be more effective or safer than morphine&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">But the best option for these patients is a slow and progressive withdrawal of the opioid until it is suppressed&#44; while other pharmacological alternatives that do not contain opioids and non-pharmacological therapies for the treatment of pain can be sought&#46; The speed and duration of the withdrawal period will be adjusted according to the patient&#39;s response&#44; to minimise withdrawal symptoms&#46; In general&#44; the reduction will be slower in patients who have been on opioid treatment for a longer time&#44; who are afraid of the withdrawal process&#44; and&#47;or who have cardiorespiratory diseases or opioid use disorder&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">A suitable guideline for the opioid withdrawal process is decreasing the dose by approximately 10&#37; of the initial dose every one or two weeks&#44; or 25&#37; of the current dose every three or four weeks&#46; After reaching one third of the initial dose&#44; reduction should be slower &#40;5<span class="elsevierStyleHsp" style=""></span>mg or less every 2&#8211;4 weeks&#41;&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Multidisciplinary programmes are recommended in cases where dose reduction is complicated&#44; with a coordinated collaboration between a variety of professionals &#40;PC team&#44; physiotherapist&#44; occupational therapist&#44; pharmacist&#44; pain specialist&#44; psychologist&#44; psychiatrist&#44; etc&#46;&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">If this structured treatment fails&#44; a priority referral to an addiction service is indicated&#44; where methadone or buprenorphine&#47;naloxone treatment will be assessed&#46; There is a group of professionals who believe that primary care physicians or other prescribing specialists should be adequately trained to address these issues given that the problems related to opioid analgesics are becoming more frequent&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">25</span></a> Additionally&#44; we must not forget the importance of psychosocial interventions in these patients and the current lack in Spain of specialist professionals in this area within primary care teams&#44; which makes comprehensive treatment difficult&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Assisted treatment with medication</span><p id="par0225" class="elsevierStylePara elsevierViewall">Medication-assisted treatment comprises the prescription of controlled amounts of long-acting opioid drugs within a comprehensive treatment programme that includes psychosocial interventions from the beginning&#46; Spain has traditionally used three opioid drugs for this type of treatment&#58; &#40;a&#41; <span class="elsevierStyleItalic">naltrexone</span> &#40;antagonist&#41;&#44; &#40;b&#41; <span class="elsevierStyleItalic">methadone</span> &#40;pure agonist&#41; and &#40;c&#41; <span class="elsevierStyleItalic">buprenorphine&#47;naloxone</span> &#40;partial agonist&#41;&#46; The efficacy of agonist treatments &#40;methadone and buprenorphine&#47;naloxone&#41; has been clearly demonstrated&#44; while the evidence for naltrexone treatments is poor&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Although methadone has a greater experience of use and seems to show better retention rates in treatment&#44; buprenorphine&#47;naloxone has a more favourable safety profile and is a safe&#44; effective and profitable option<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a>&#59; however&#44; the fact that it is only partially financed by the national health system may limit its use in patients with a more depressed socioeconomic status&#46; The priority for patients who are at high risk of abandoning treatment is retention&#44; and as such they will most probably benefit more from a methadone maintenance programme&#46; However&#44; for patients with a high risk of toxicity&#44; safety is the first consideration and as such they are clearly candidates for buprenorphine&#8211;naloxone replacement therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">In general&#44; patients treated with buprenorphine&#47;naloxone report several advantages over methadone&#44; such as a &#8216;clearer state of mind&#8217;&#44; less concentration difficulties&#44; less social stigma&#44; less drowsiness&#44; greater decrease in desire for consumption and a simpler withdrawal when the end of substitution treatment is decided&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> In short&#44; the choice of methadone or buprenorphine&#47;naloxone will depend on severity&#59; concomitant medication&#59; social context<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a>&#59; individual pharmacological and clinical parameters &#40;efficacy&#44; safety&#44; pharmacological interactions&#44; quality of life&#44; medical or psychiatric comorbidities&#41;&#59; patient&#39;s preferences &#40;abstinence and recovery&#44; or harm reduction&#41; and the prescribing physician&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Although there is not much or at most a moderate amount of evidence supporting the effectiveness of these treatments in patients with prescription opioid disorder&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> most of the current guidelines recommend them as the most favourable option&#44;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">6&#44;31&#44;32</span></a> obtaining better results with long-term treatments&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">While other professionals are not adequately trained&#44; the conversion of the dose of any opioid to methadone or buprenorphine&#47;naloxone equivalents should only be carried out by professionals who are experts in the treatment of these drugs&#44; such that these treatments&#44; for the time being&#44; should be carried out only in specialised addiction services&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">In the same way as with heroin&#44; there is no reliable equianalgesic table that allows us to calculate the exact dose of methadone or buprenorphine&#47;naloxone equivalent to a given dose of any opioid analgesic&#46; The most prudent course is to start treatment with a low dose of the substitute drug and adjust it according to clinical criteria&#44; the patient&#39;s well-being and the need for a rescue dose&#46; The majority of patients benefit from the dosage of the substitute divided into two or three doses per day&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Methadone&#46;</span> Methadone is a synthetic opioid agonist that eliminates the symptoms of withdrawal syndrome and decreases the compulsive desire to consume other opioids&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In patients with opioid use disorder analgesics should always start with low doses &#40;15&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; divided into two or three daily doses&#41;&#46; The patient will be evaluated every 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#44; adjusting the methadone dose upwards &#40;never increasing more than 30&#8211;50&#37; of the initial dose&#41; or downwards&#44; according to clinical criteria and the patient&#39;s response&#44; while simultaneously reducing the daily dose of the opioid being abused by 30&#8211;50&#37;&#44; withdrawing it in 3&#8211;4 days&#46; Until a stable dose of methadone is reached&#44; using non-opioid analgesics for the treatment of pain is appropriate&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">In most cases&#44; the administration of methadone may be performed on an outpatient basis&#46; If a hospital admission was required&#44; depending on the profile of each patient&#44; it would ideally be&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">a&#46;</span><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In the Pain Unit &#40;if beds are available&#41; or in the Internal Medicine Service&#46;</span> For patients who do not have adequate social support or are afraid of the change&#44; withdrawal or pain syndromes&#59; a psychiatric comorbidity &#40;including a history or active consumption of alcohol or other drugs&#41;&#44; or a medical comorbidity&#44; or who do&#44; but they are stabilised and not serious&#44; when decompensation is not foreseeable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">b&#46;</span><p id="par0275" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hospital admission to the Mental Health Service &#40;short hospitalisation unit&#41;&#46;</span> For patients without significant medical comorbidity&#59; with a history of psychiatric comorbidity &#40;including a history or active consumption of alcohol or other drugs&#41;&#44; or a current mental illness that has not been stabilised or is at risk of destabilisation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">c&#46;</span><p id="par0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hospital admission into intensive care&#46;</span> For elderly patients&#59; patients with significant decompensated medical comorbidity or those at risk of decompensation&#44; or for those who have an intrathecal morphine pump&#46;</p></li></ul></p><p id="par0285" class="elsevierStylePara elsevierViewall">In all cases&#44; a treatment contract should be signed that contains information on the treatment to be carried out and the general and specific rules for each service&#46; Patient monitoring and treatment should be carried out by the specialists of each service&#44; in close coordination and collaboration with specialists from the Pain Unit and the Addiction Service&#44; who should be available for any required consultation or action&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Patient monitoring and treatment is the responsibility of the addiction service specialist&#44; with the collaboration of professionals from the other services&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Buprenorphine&#47;naloxone&#46;</span> Buprenorphine is a partial opioid agonist&#44; with agonist or antagonist properties depending on the presence or absence of other opioids in the body&#46; For this reason&#44; waiting some time after the last dose of the opioid that is being abused is necessary&#44; so as not to precipitate withdrawal syndrome&#46; Induction should not be started until mild&#47;moderate signs and symptoms are observed&#44; which can be evaluated with the <span class="elsevierStyleItalic">Clinical Opiate Withdrawal Scale</span>&#44; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; where a score of &#8805;8 is considered to be confirmation&#46; In general&#44; we can prevent the precipitation of the withdrawal syndrome if we wait for the following times from the last dose of the opioid that is being abused&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0300" class="elsevierStylePara elsevierViewall">Heroin and ultrafast release opioids&#58; 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0305" class="elsevierStylePara elsevierViewall">Immediate release opioids&#58; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0310" class="elsevierStylePara elsevierViewall">Methadone and prolonged-release opioids&#58; 36&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0315" class="elsevierStylePara elsevierViewall">Transdermal patches&#58; 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0320" class="elsevierStylePara elsevierViewall">Buprenorphine&#47;naloxone tablets &#40;2&#47;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg and 8&#47;2<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; administered sublingually&#46; Naloxone does not produce any clinical effect when administered this way&#59; it only has an antagonistic effect when administered intravenously&#59; it is present in tablet form to discourage its injection&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Administration is carried out in the same way as it is for heroin users and is equally effective&#46; The purpose is to administer the minimum dose to ensure the patient does not present withdrawal symptoms&#44; but does achieve adequate opioid block&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">As a prior period without opioids is required &#40;moderate withdrawal&#41;&#44; in some cases these patients will need to be hospitalised&#44; in order to properly control withdrawal symptoms&#46; Outpatient administration may be attempted in patients who have a strong social support network&#44; are highly motivated&#44; are predisposed to the process and have an adequate understanding of the treatment and possible withdrawal symptoms that may appear&#46; The criteria for the induction of buprenorphine&#8211;naloxone in a hospital setting will be the same as those indicated in the methadone summary&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusion</span><p id="par0335" class="elsevierStylePara elsevierViewall">Patients with chronic pain treated with opioid analgesics &#40;both chronic&#44; non-cancer pain and cancer pain associated with high survival rates in the medium&#47;long term&#41; are complex and pose a challenge for medicine&#46; The situation can be complicated when long-term treatments with opioid analgesics are used at high doses&#44; since it increases the risk of serious adverse effects related to these drugs&#46; In clinical trials compared to placebo&#44; opioid analgesics show an absolute rate of adverse effects of 78&#37;&#44; with 7&#46;5&#37; of these being severe effects&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> However&#44; there is no reliable information on addiction or other expected adverse effects from the continued use of opioids &#40;alterations in mood&#44; sleep apnoea&#44; sexual dysfunction or hypogonadism&#41;&#46; Some of these adverse effects appear after a latency period and most of the studies do not follow the patients beyond six months&#46; This is a significant limitation to the evidence needed&#44; which means that carrying out systematic studies with long-term follow-ups is essential in order to obtain more reliable data on the prevalence of all the adverse effects related to these drugs&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">There is currently no consensus on how to treat patients with chronic non-cancer pain who develop a disorder to using prescription opioids&#46; Establishing personalised and multidisciplinary strategies&#44; with the collaboration and coordination of all health-care areas is recommended&#46; For the time being&#44; assisted treatments with opioid agonists seem to be the most favourable option&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Finally&#44; we would like to highlight that the best treatment for disorders of opioid analgesics use is prevention&#44; through the application of strategies that can minimise the risks associated with the misuse of these drugs while maximising their effectiveness&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows some recommendations for the safe prescription of opioids&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflict of interest</span><p id="par0350" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Classification of problems related to prescription opioids"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Therapeutic error"
            ]
            1 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Tampering"
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            2 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Incorrect use"
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            3 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Abstinence syndrome"
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            4 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Overdose"
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              "identificador" => "sec0035"
              "titulo" => "Aberrant behaviour"
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              "identificador" => "sec0040"
              "titulo" => "Opioid use disorder"
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          ]
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        1 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Dependence vs&#46; addiction"
        ]
        2 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Prevention and treatment of overdoses by opioid analgesics"
        ]
        3 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Effective treatments of disorders by use of prescription opioids"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Treatment based on abstinence"
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            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Structured treatment with opioids"
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            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Assisted treatment with medication"
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          ]
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        4 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conclusion"
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        5 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflict of interest"
        ]
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          "titulo" => "References"
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    "fechaRecibido" => "2018-09-10"
    "fechaAceptado" => "2018-10-16"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Henche Ruiz AI&#46; Uso problem&#225;tico de los analg&#233;sicos opioides de prescripci&#243;n&#58; clasificaci&#243;n y tratamientos eficaces&#46; Med Clin &#40;Barc&#41;&#46; 2019&#59;152&#58;458&#8211;465&#46;</p>"
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    "apendice" => array:1 [
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        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par9120" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0910"
          ]
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                  <table border="0" frame="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46; Frequent consumption of higher amounts or for longer than expected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Persistent desire or unsuccessful efforts to cut down or control opioid use&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46; Great deal of time spent on activities associated with its consumption &#40;obtaining&#44; using or recover from the opioid&#39;s effects&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46; Craving or a strong desire to use opioids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46; Recurrent opioid use resulting in a failure to fulfil major role obligations at work&#44; school&#44; or home&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46; Continued opioid use&#44; despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46; Important social&#44; occupational&#44; or recreational activities are given up or reduced because of opioid use&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">8&#46; Recurrent opioid use in situations in which it is physically hazardous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46; Continued opioid use&#44; despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46; Tolerance<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46; Withdrawal syndrome<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Criteria for diagnosis of opioid use disorder &#40;DSM-5&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t">- Median age &#40;45&#8211;65&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- No personal history of alcohol or other drug use&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Chronic pain that is difficult to treat&#44; with a long history of ineffective treatments &#40;&#8216;revolving door&#8217; patients&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Significant functional deterioration&#44; with substantial limitations to quality of life&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Intense psychosocial stress and marked emotional component of pain&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">- High rates of psychiatric comorbidity &#40;depressive disorders&#44; anxiety disorders&#44; disorders related to traumas and stress factors&#44; personality disorders&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prolonged treatment with high doses of one or more opioids&#44; one of them frequently being transmucosal fentanyl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Compulsive need to take prescribed opioids&#44; even when they do not relieve pain&#44; without being able to clearly determine the reasons&#44; among which are the memory of untreated pain&#44; pain relief&#44; withdrawal symptoms or psychological discomfort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Profile of patients with problematic use of opioid analgesics&#46;</p>"
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">BDZ&#58; benzodiazepines&#59; ICU&#58; intensive care unit&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A-2-adrenergic agonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clonidine</span> &#40;oral tablets of 0&#46;150<span class="elsevierStyleHsp" style=""></span>mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Day 1</span>&#58; 1&#8211;2 tablets every 8<span class="elsevierStyleHsp" style=""></span>h&#44; adjusting the dose according to abstinence symptoms&#46; Maximum&#58; 1<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleItalic">Days 2&#8211;4</span>&#58; 2&#8211;3 tablets every 8<span class="elsevierStyleHsp" style=""></span>h&#44; adjusting the dose according to abstinence symptoms&#46; Maximum&#58; 1&#46;3<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleItalic">From day 5</span>&#58; reduce to 1 tablet per day until suspension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">They reduce abdominal pain&#44; chills&#44; muscle cramps&#44; irritability and restlessness&#46;They do not act on anxiety or insomnia&#46;They require monitoring of the cardiovascular constants&#44; since they can produce bradycardia and intense arterial hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tizanidine &#40;oral tablets of 2 and 4<span class="elsevierStyleHsp" style=""></span>mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;4<span class="elsevierStyleHsp" style=""></span>mg per day&#46;When abstinence is controlled&#44; reduce to 1 tablet per day until suspension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sedative neuroleptics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Quetiapine</span><span class="elsevierStyleItalic">Olanzapine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#8211;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day5&#8211;10<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">They reduce agitation and anxiety&#46; Atypical neuroleptics are recommended&#46; Once the profile has been stabilised&#44; a progressive reduction of the dose is carried out until suspension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Long-acting myorelaxing anxiolytics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Diazepam</span><span class="elsevierStyleItalic">Clonazepam</span><span class="elsevierStyleItalic">Dipotassium chloracepate</span><span class="elsevierStyleItalic">Ketazolam</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8211;25<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h1&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h25&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h15&#8211;30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">They reduce the anxiety and agitation that accompany abstinence symptoms&#46; After achieving stabilisation &#40;3&#8211;4 days&#41;&#44; progressively decrease the dose until suspension&#46; Ten days of treatment usually suffice&#46; Prolonging treatment beyond two months is not recommended due to the high risk of abuse or addiction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiepileptics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gabapentina</span><span class="elsevierStyleItalic">Pregabalin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&#8211;800<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h150&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Useful for stabilising patients&#8217; mood and controlling pain with neuropathic characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sedative antidepressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Trazodione</span><span class="elsevierStyleItalic">Mirtazapine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#8211;100<span class="elsevierStyleHsp" style=""></span>mg in the evening15&#8211;45<span class="elsevierStyleHsp" style=""></span>mg in the evening&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Improve patients&#8217; sleep patterns&#44; without the high risk of abusing BZDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-opioid analgesics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antipyretic analgesics &#40;<span class="elsevierStyleItalic">paracetamol&#44; metamizole</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At usual doses&#44; they reduce the musculoskeletal pain and fever associated with the withdrawal syndrome&#46; Classical NSAIDs present a higher gastrointestinal risk&#44; while COXIB present higher cardiovascular risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#58;<span class="elsevierStyleHsp" style=""></span>Classical NSAIDs &#40;<span class="elsevierStyleItalic">ibuprofen&#44; ibuprofen&#8211;arginine&#44; naproxen&#44; ketorolac&#44; dexketoprofen&#44; diclofenac&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">COX-2 &#40;<span class="elsevierStyleItalic">celecoxib</span>&#44; <span class="elsevierStyleItalic">etoricoxib</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiemetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Metoclopramide</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;oral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Domperidone</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h &#40;oral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ondansetron</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8211;8<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h &#40;oral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antidiarrheals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mebevirin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">135<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&#44; 20<span class="elsevierStyleHsp" style=""></span>min before the main meal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Loperamide</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>mg after each bowel movement &#40;maximum&#58; 16<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Racecadotril</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&#44; before the main meals&#46; For a maximum of 7 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Powerful sedatives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Propofol</span><span class="elsevierStyleItalic">Midazolam</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In bolus or perfusion&#46;They require close monitoring of the patient&#59; administration should only be carried out by professionals who are experts in the treatment of these drugs&#44; such that their use will be limited to detoxification in the ICU&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047636.png"
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Most commonly used drugs for opioid detoxification&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
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          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Adapted and translated from Wesson D&#46;R&#46; and Ling W&#46;&#8217;s The Clinical Opiate Withdrawal Scale &#40;COWS&#41;&#46; J Psychoactive Drugs&#46; 2003&#59; 35&#58;253&#8211;9&#46;</p>"
          "tablatextoimagen" => array:12 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Resting pulse rate &#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95;&#95; beats&#47;minute</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;measure after the patient has been sitting or lying down for one minute&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Pulse rate of 80 or below&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Pulse rate of 81&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Pulse rate of 101&#8211;120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Pulse rate greater than 120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047646.png"
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sweating</span> &#40;during the last 30 minutes&#59; not due to room temperature or patient activity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 No report of chills or flashing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Subjective report of chills or flashing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Flushed or observable moistness on face&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 Beads of sweat on brow or face&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Sweat streaming off face&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047647.png"
              ]
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            2 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Restlessness</span> &#40;observation during assessment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Able to remain sit still&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Reports difficulty sitting still&#44; but is able to do so&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 Frequent shifting or extraneous movements of legs&#47;arms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5 Unable to sit still for more than a few seconds&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047639.png"
              ]
            ]
            3 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pupil size</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Pupils pinned or normal size for room light&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Pupils possibly larger than normal for room light&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Pupils moderately dilated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5 Pupils so dilated that only the rim of the iris is visible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047643.png"
              ]
            ]
            4 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bone or articular</span> pain &#40;if patient was previously suffering from pain&#44; only the additional component attributed to opiates withdrawal is scored&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Absence of pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Mild&#44; diffuse discomfort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Patient reports severe diffuse aching of articulations&#47;muscles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Patient rubs articulations or muscles and is unable to sit still because of discomfort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047637.png"
              ]
            ]
            5 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Rhinorrhea</span> &#40;runny nose&#41; or <span class="elsevierStyleItalic">tearing</span> &#40;not accounted for by cold&#47;flu symptoms or allergies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Not present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Nasal congestion or unusually moist eyes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Rhinorrhea or obvious tearing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Constant rhinorrhea or tears streaming down cheeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2047649.png"
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            ]
            6 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Digestive discomfort</span> &#40;during the last 30 min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Absence of digestive symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Stomach cramps&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Nausea or loose stools&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 Vomiting or diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5 Multiple episodes of diarrhoea or vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047650.png"
              ]
            ]
            7 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tremors</span> &#40;observation of outstretched hands&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 No tremor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Tremor can be felt&#44; but not observed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Slight tremor observable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Considerable trembling or muscle contractions&#47;twitching&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047642.png"
              ]
            ]
            8 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Yawning</span> &#40;observation during assessment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 No yawning&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Yawning once or twice during assessment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 Yawning three or more times during assessment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 Yawning several times&#47;minute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047648.png"
              ]
            ]
            9 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Anxiety or irritability</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 No anxiety or irritability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 Patient reports increasing irritability or anxiousness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 The patient is obviously irritable or anxious&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4 The patient is so irritable or anxious that participation in the assessment is difficult&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047635.png"
              ]
            ]
            10 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Piloerection</span> &#40;goose flesh skin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0 Soft skin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 Piloerrection of skin can be felt or hairs standing up on arms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5 Prominent piloerection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047640.png"
              ]
            ]
            11 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total score</span> &#40;sum of the 11 items&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mild&#58; 5&#8211;12&#59; Moderate&#58; 13&#8211;24&#59; Moderately severe&#58; 25&#8211;36&#59; Severe withdrawal&#58; &#8805;36&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2047638.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical Opiate Withdrawal Scale &#40;COWS&#41;&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46; Pain management must always be personalised&#44; with a comprehensive&#44; multidisciplinary and structured approach from the beginning of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; A complete clinical evaluation should be carried out that includes not only an assessment of pain&#44; but also of the patients&#8217; functional status&#44; quality of life and potential risk of overdose and opioid abuse&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46; The patient should be clearly and completely informed about the treatment &#40;benefits and possible risks&#44; including addiction and overdose&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46; Always following the WHO analgesic ladder&#44; to ensure a progressive approach is advisable&#46; Opioid analgesics are not first-line drugs in the treatment of chronic&#44; nociceptive or neuropathic pain&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46; Although no absolute contraindications have been established for the use of opioids for the treatment of chronic pain&#44; there is evidence that in some cases its use is not recommended &#40;e&#46;g&#46; primary headache&#44; fibromyalgia&#44; current or past substance use disorder&#44; major depressive disorder and&#47;or suicidal tendencies&#44; irritable bowel syndrome&#44; etc&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46; In general&#44; treatment with opioid analgesics should only be considered in those cases of moderate&#47;intense nociceptive pain&#44; when these two circumstances occur&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Previous failure of all possible non-opioid treatments&#44; including minimally invasive techniques&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Expectations of short-term resolution of the main origin of pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46; Only a small proportion of patients with chronic non-cancer pain will benefit from opioid treatment&#44; and their effectiveness is not clearly established over 6&#8211;12 months&#46; Accepting that opioid treatment may fail is the first step in improving its use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46; The more chronic and complex the pain and the younger the patient&#44; the less indicated opioids are&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46; In patients with a history of drug abuse&#44; psychiatric illness or misuse of medications&#44; treatment with opioids should only be considered if close control can be guaranteed&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46; Long-term treatment&#44; especially at high doses&#44; increases the risk of overdose and addiction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46; The concomitant use of benzodiazepines&#44; alcohol or other central nervous system depressants&#44; together with opioids&#44; increases the risk of overdose&#44; so they should be avoided&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46; One must always bear in mind&#44; from the beginning of treatment&#44; the emotional component of chronic pain&#44; which must also be appropriately treated&#46; If we do not address that issue&#44; we run the risk of perpetuating the pain and disability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46; Dose adjustment will be made with immediate release formulations &#40;lower risk of overdose&#41;&#46; Once the minimum effective dose is reached&#44; the patient can be transferred to prolonged-release formulations &#40;lower risk of addiction&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46; There is no evidence of greater analgesic efficacy of any opioid compared to the rest&#46; The powerful opioid analgesic of choice continues to be morphine&#44; due to its greater experience of use and because it is the most cost-effective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46; Transmucosal fentanyl formulations in adequate doses are only indicated for breakthrough pain in cancer patients who are already undergoing treatment with another opioid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46; Reanalysis must be carried out periodically &#40;max&#46; every 3 months&#44; but more often for patients whose morphine equivalent dose &#40;MED&#41; is more than 50<span class="elsevierStyleHsp" style=""></span>mg&#41; for&#58; pain&#44; function&#44; quality of life&#44; risk of overdose or misuse&#44; presence of psychiatric comorbidity&#44; compliance with non-opioid treatments prescribed&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46; In patients whose MED is 90<span class="elsevierStyleHsp" style=""></span>mg for more than 6 months&#44; trying to reduce the dose to verify that the analgesic effect is maintained is indicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46; If an opioid at moderate doses does not work&#44; rotation to another opioid from a different group is indicated&#46; The following is NOT indicated&#58;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Increasing doses to unacceptable levels&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>The addition of another opioid by the same or a different administration route &#40;including transmucosal fentanyl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">19&#46; All patients requiring MED higher than 120<span class="elsevierStyleHsp" style=""></span>mg who have uncontrolled pain should be categorised as differential diagnosis of opioid-induced hyperalgesia&#44; opioid use disorder or treatment failure&#44; and should be referred to the Reference Pain Unit&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">20&#46; The slow and progressive reduction of opioid treatment until suppression&#44; if possible&#44; will be indicated in the following cases&#58;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>The patient has requested it&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MED of &#8805;50<span class="elsevierStyleHsp" style=""></span>mg per day are being administered without a clear benefit&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Signs of a disorder of other substances&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Founded suspicion or certainty of problems related to the use of opioid analgesics&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">If in all these cases complete withdrawal of the opioid is not possible&#44; initiating treatment with agonists &#40;methadone or buprenorphine&#47;naloxone&#41; is recommended&#46;&nbsp;\t\t\t\t\t\t\n
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