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history of barbiturates

-1864 barbituiric acid synthesized by Baeyer (before aspirin)
-barbituric acid used to make first barb, called barbital (Veronal)-1903

uses for barbiturates

-general anesthetic for surgery
-epilepsy anticonvulsant
-maintain coma in emergency trauma
-anxiety and sleep uses now obsolete

categories of barbiturates

-differ from each other in duration of effect
-short acting drug-anesthetic
-short to medium for sedation and sleep
-long-acting one for sedation or anticonvulsant

barbiturate problems (3)

* replaced by benzodiazepines in 1960s
1. rapid development of tolerance to sedative effect-can increase enzyme induction-but no tolerance to lethal effect of respiratory depression
2. narrow TI-overdose risk great
3. interact dangerously with many other drugs

barbiturate withdrawal

-can be mild at low doses (less than 400mg/day)
REM rebound, sleep disturbances
-serious (around 800mg/day) similar to alcohol: tremors, anxiety, nausea, delirium, seizures, death

physical dependence

occurs when 4 to 6 times the average hypnotic dose is taken for a long time (2-6 months after starting to increase)


-iatrogenic: patients don't want to stop taking the drug, escalate doses, come back for early refills
-street use: higher doses taken in binges rather than continuously, mixed w/ other drugs
-rats and monkeys will self-administer in low doses that don't cause physical dependence


-not clear if they are substantially teratogenic (birth defect causing)
-birth defects (produced by many anticonvulsants given for epilepsy during pregnancy)
-most common birth defects: heart, skeleton, CNS, cleft palate, malformation of male genitals
-newborn of dependent mother goes through withdrawal: high pitched cry, tremors, delirium, seizures


-acts synergistically w/ alcohol
ex. half the lethal dose of barbital and 1/4 the lethal dose of alcohol=deadly
-used to be a common drug for suicide
-lethal dose does not show the same degree of tolerance as dose for intoxication
-4,000-6,000 is lethal range. but combined w/ alcohol is much lower

mechanism of action

-increases effect of GABA at the receptor: opens the channel and lets chloride in
-may open cl- channels at high concentrations, this is why overdose can be fatal
-can increase the amount of time the ion channel stays open
-have an anxiolytic effect

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