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    OPIOID WITHDRAWAL

    DEFINITION

    Clinical syndrome produced by withdrawal of an opioid drug from an
    opioid-dependent individual.

    by:  (1) the cessation or abrupt reduction in dosage of an opioid; or
    (2) the administration of an opioid antagonist.

    TOXIC CAUSES

    Administration of an opioid antagonist including:
         Naloxone 
         Naltrexone 
         Nalorphine

    For this reason, in opioid-dependent individuals, opioid antagonists
    should be used with caution.

    NON-TOXIC CAUSES

    Cessation or reduction in dose of an opioid drug including:
         Buprenorphine 
         Butorphanol 
         Codeine 
         Fentanyl 
         Heroin (Diamorphine) 
         Hydrocodone 
         Hydromorphine 
         Levorphanol 
         Meperidine (Pethidine) 
         Methadone 
         Morphine 
         Nalbuphine 
         Oxycodone 
         Oxymorphone 
         Pentazocine 
         Phenoperidine 
         Propoxyphene 

    CLINICAL DIAGNOSIS

    A history of cessation or abrupt reduction in dosage of an opioid, or
    the administration of an opioid antagonist, in an opioid-dependent
    individual.

    Initial symptoms and signs may develop immediately after the
    administration of an opioid antagonist or up to 48 hours after
    cessation or reduction in dosage of the opioid, depending upon the
    half-life of the drug concerned.  These include restlessness,
    mydriasis, lacrimation, rhinorrhea, sneezing, piloerection, yawning,
    perspiration, restless sleep and aggressive behavior.  Severe

    manifestations include: muscle spasms, back aches, abdominal cramps,
    hot and cold flashes, insomnia, nausea, vomiting, diarrhoea,
    tachypnoea, hypertension, hypotension, tachycardia, bradycardia and
    cardiac dysrhythmias.  Seizures may be observed in neonates (only).

    DIFFERENTIAL DIAGNOSIS

    Ethanol or benzodiazepine withdrawal
    Psychogenic origin
    Simulated withdrawal

    Other toxic states may mimic certain features of opioid withdrawal.

    RELEVANT INVESTIGATIONS

    Serum electrolytes (Na, K, Cl), creatinine, blood glucose and
    hematocrit may be of value in managing patients and should be ordered
    as necessary. Similarly, an ECG, arterial blood gas analysis and renal
    function tests may be judged to be necessary clinically.

    TREATMENT

    The management of the withdrawal syndrome should not be exclusively
    pharmacological in nature but should include a full evaluation of the
    patient to determine the most appropriate approach to therapy.  One of
    two general approaches is commonly adopted.  The first comprises
    substitution of the drug with a longer-acting opioid, such as
     methadone, followed by a gradual reduction in dosage of the
    substitute drug. The second comprises use of various pharmacological
    agents, such as  clonidine and/or a  benzodiazapine, which will
    mitigate symptoms and signs of withdrawal. Psychological support may
    be necessary. Indeed, some schools of thought contend that
    psycho-social support alone is the only effective treatment for
    opioid withdrawal states.

    When  clonidine is employed, the dose is 0.006 mg/kg/day, in divided
    doses, adjusted as necessary according to withdrawal symptoms and
     clonidine side-effects (such as sedation and/or postural
    hypotension). The dosage of  clonidine should then be gradually
    reduced, typically over a one- to two-week period. 

    If symptoms and signs of opioid withdrawal do not respond to the use
    of  clonidine and/or  benzodiazepines, then the use of
     propantheline (for stomach cramps) or  atropine (for diarrhoea) may
    be considered.  

    Opioid-dependent individuals with co-existent medical or surgical
    conditions requiring pain relief should receive conventional
    treatment, including if necessary the administration of  opioids.

    CLINICAL COURSE AND MONITORING

    The time course and severity of opioid withdrawal depends on the
    opioid involved and the use history of the individual.  That following
    withdrawal of morphine, has an onset at about 12 hours after the last
    dose, peaks within 48 to 72 hours and resolves over a period of days. 
    Withdrawal of shorter-acting opioids (e.g. meperidine) produces a
    shorter more intense clinical syndrome.  Withdrawal of longer-acting
    opioids such as methadone produced a withdrawal syndrome with a more
    delayed onset, milder severity and prolonged duration.

    The withdrawal syndrome produced by administration of naloxone is
    intense, occurs within five minutes, peaks at approximately 30 minutes
    and subsides within 2 hours.

    The management of the opioid withdrawal syndrome should include
    admission to hospital with monitoring of haemodynamic status, pupil
    size, and bowel sounds. The patient should be placed in a quiet, dark
    and comfortable environment. Where relevant, it is important to ensure
    that the patient does not continue to receive an illicit supply of
    opioid.  

    AUTHOR(S)/REVIEWERS

    Author:        K. Hartigan-Go National Poisons Control and Information
                   Service, Manila, Phillipines.

    Peer Review:   Cardiff 3/95,  Berlin 10/95: V. Danel, T. Meredith,
                   A. Nantel, L. Murray, A. Wong, J. Pronczuk.