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546 SecTioN iii Neurology aNd Special SeNSeS ` neurology—PhArmACology Neurology aNd Special SeNSeS ` neurology—PhArmACology
Barbiturates Phenobarbital, pentobarbital, thiopental, secobarbital.
−
meChAnism Facilitate GABA action by duration of Cl channel opening, thus neuron firing (barbidurates
A
duration).
CliniCAl use Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
AdVerse eFFeCts Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by
alcohol use); dependence; drug interactions (induces cytochrome P-450).
Overdose treatment is supportive (assist respiration and maintain BP).
Contraindicated in porphyria.
Benzodiazepines Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide,
alprazolam.
–
meChAnism Facilitate GABA action by frequency of Cl channel opening (“frenzodiazepines” frequency).
A
REM sleep. Most have long half-lives and active metabolites (exceptions [ATOM]: Alprazolam,
Triazolam, Oxazepam, and Midazolam are short acting higher addictive potential).
CliniCAl use Anxiety, panic disorder, spasticity, status epilepticus (lorazepam, diazepam, midazolam), eclampsia,
detoxification (especially alcohol withdrawal– DTs), night terrors, sleepwalking, general anesthetic
(amnesia, muscle relaxation), hypnotic (insomnia). Lorazepam, Oxazepam, and Temazepam can
be used for those with liver disease who drink a LOT due to minimal first-pass metabolism.
AdVerse eFFeCts Dependence, additive CNS depression effects with alcohol and barbiturates (all bind the GABA
A
receptor). Less risk of respiratory depression and coma than with barbiturates. Treat overdose with
flumazenil (competitive antagonist at GABA benzodiazepine receptor). Can precipitate seizures
by causing acute benzodiazepine withdrawal.
Nonbenzodiazepine Zolpidem, Zaleplon, esZopiclone. “These ZZZs put you to sleep.”
hypnotics
meChAnism Act via the BZ subtype of the GABA receptor. Effects reversed by flumazenil. Sleep cycle less
1
affected as compared with benzodiazepine hypnotics.
CliniCAl use Insomnia.
AdVerse eFFeCts Ataxia, headaches, confusion. Short duration because of rapid metabolism by liver enzymes. Unlike
older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic
effects. dependence risk than benzodiazepines.
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