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Barbiturate Withdrawal


BARBITURATE WITHDRAWAL Liz Thomas Morning Report March 4, 2008 * * * * * * * * * Sedative-hypnotic drugs Sedatives lower excitement and calm the awake patient, and ... – PowerPoint PPT presentation

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Title: Barbiturate Withdrawal

Barbiturate Withdrawal
  • Liz Thomas
  • Morning Report
  • March 4, 2008

Sedative-hypnotic drugs
  • Sedatives lower excitement and calm the awake
    patient, and hypnotics induce drowsiness and
    promote sleep
  • Includes benzodiazepines, barbiturates and other
  • Barbituric acid was first discovered in 1864 and
    introduced to clinical practice in 1903
  • Phenobarbital and pentobarbital were long used as
    anxiolytics but have now been largely replaced by
    benzodiazepines due less potential for abuse or
    fatal overdose

  • Benzodiazepines are more specifically anxiolytic
    and do not produce surgical anesthesia, coma or
    death (even at high doses) unless given with
    other agents which suppress respiration
  • Barbiturates, however, have a low therapeutic
    index and fatal overdose can occur with doses
    easily achieved with the number of pills often
    dispensed in a single prescription

  • Reversibly suppress the activity of all excitable
    tissue, including CNS activity, along a
    dose-dependent continuum
  • Affect the GABA system producing cross tolerance
    to other sedating drugs (ETOH, benzodiazepines)
  • Rapid development of tolerance is common and
    leads to a tendency for patients to raise the
    dose with chronic use

  • Most commonly used barbiturates today are
    amobarbital (Amytal), butabarbital (Butisol),
    mephobarbital (Mebaral), pentobarbital
    (Nembutal), secobarbital (Seconal), butalbital
    (Fioricet/Fiorinal), and phenobarbital (Luminal)
  • All have an intermediate duration of action,
    except phenobarbital which has a long duration of

  • Intoxication with barbiturates is very similar to
    alcohol intoxication
  • Symptoms include sluggishness, incoordination,
    difficulty thinking, poor memory, slow speech,
    disinhibition, emotional lability
  • Physical signs include nystagmus and decreased
  • CNS effects progress to sleep, unconsciousness,
    coma, surgical anesthesia and ultimately fatal
    respiratory and cardiovascular depression

  • Management of acute intoxication is generally
    supportive, including maintenance of adequate
    airway, ventilation and cardiovascular function
  • Activated charcoal should be given to prevent
    further GI absorption of the ingested drug and
    prevent active metabolites from being absorbed
    through enterohepatic circulation
  • Barbiturate overdose should be treated with urine
    alkalinization to increase drug excretion
  • Sodium bicarbonate should be given at sufficient
    dose to maintain urine pH of 7.5
  • Dialysis may be necessary in some cases

  • Although abuse of barbiturates has been declining
    since its height in the 1970s, there are some
    reports that abuse is increasing in high school
  • The most commonly abused barbiturates are
    amobarbital (Amytal), pentobarbital (Nembutal),
    and secobarbital (Seconal).

  • Analgesics containing short- to
    intermediate-acting barbiturates with various
    combinations of aspirin, acetaminophen and
    caffeine are widely prescribed for migraine and
    tension headaches (Fiorinal, Fioricet, Phrenelin,
  • However, there is a lack of good data for this
    use. Such analgesics have been banned in Germany
    and expert advisory panels elsewhere have pointed
    out the potential for abuse

  • It is generally accepted that overuse of these
    medications can lead to chronic daily headache
    (rebound headache) in which escalating
    ingestion of the medication is accompanied by
    escalating headache
  • Attempts to stop the medication may be
    accompanied by withdrawal symptoms or even
  • These medications can be obtained over the
    internet without a prescription

  • All medicines that influence the GABA system show
    cross-tolerance and similar withdrawal patterns
  • Removal of GABA-ergic inhibitory tone in the
    central nervous system has been proposed to cause
    HTN, tachycardia, diaphoresis, tremors,
    hyperthermia and seizures
  • Sedative-hypnotics are potent antiepileptics that
    raise the seizure threshold, so when abruptly
    discontinued they produce a rebound drop in the
    seizure threshold that may cause seizures even in
    patients without a history of prior seizures
  • Withdrawal usually occurs within 8 36 hours,
    but can be seen up to 7 days following
    discontinuation of the drug

Symptoms and signs of withdrawal
  • Elevated body temperature
  • Increased blood pressure
  • Increased heart rate and respiratory rate
  • Aroused level of consciousness or frank delirium
  • Tremulousness
  • Increased reflexes
  • Disorientation
  • Pyschotic behavior including hallucinations

Treatment of withdrawal
  • Severe withdrawal, manifested by abnormal vital
    signs and/or delirium should be treated
    aggressively in an intensive care environment
  • Withdrawal can be treated with benzodiazepines,
    but it has also been suggested that barbiturate
    withdrawal should be treated with phenobarbital
    due to its longer duration of action and due to
    the fact that patients are less likely to achieve
    a high from phenobarbital

Treatment of withdrawal
  • There are no standard protocols for withdrawal in
    widespread use
  • It is generally necessary to determine the amount
    of drug taken previously and use this to
    calculate amount of medication to be administered
    in a taper
  • Treatment is challenging due to inability to
    reliably determine the amount of prior intake
  • If a patient overreports prior intake, dangerous
    intoxication can occur, and if they underreport
    intake, withdrawal seizures may result

  • Protocols have been proposed for barbiturate
    withdrawal which require loading a patient with
    phenobarbital based on patient response
  • For instance, a patient will be given
    pentobarbital 200mg by mouth, then wait one hour
    and monitor for signs of nystagmus, ataxia,
    drowsiness, dysarthria and decreased BP and
    pulse. If two or more signs are present, stop and
    convert to phenobarbital (30mg for every 100mg
    pentobarbital given, then decrease by 10 of
    initial dose every day). If not, continue to
    give 100mg pentobarbital every hour until signs
    are present or total of 600mg has been given.

  • Another protocol involves giving 120mg oral
    phenobarbital on an hourly basis until the
    patient reaches a predetermined score on a
    standardized scale
  • After this point, no further medication is
    administered and the natural slow elimination of
    the phenobarbital (half-life is 90 hours)
    minimizes the risk of withdrawal seizures

  • Loder, Elizabeth Biondi, David. Oral
    Phenobarbital Loading A Safe and Effective
    Method of Withdrawing Patients With Headache From
    Butalbital Compounds. Headache 2003 43
  • Romero, Charles Baron, Joshua, et al.
    Barbiturate Withdrawal Following Internet
    Purchase of Fioricet. Arch Neurol. 2004 61 1111
  • Silberstein, Stephen McCrory, Douglas.
    Butalbital in the Treatment of Headache History,
    Pharmacology, and Efficacy. Headache 2001 41
  • UpToDate 2008.