benzodiazepines Flashcards
describe metabolism of benzo
- ALL METABOLIZED IN LIVER (CYP3A4)
1) inactive water-soluble glucuronides (rapid metabolism, short duration)
–> Lorazepam, oxazepam
2) weakly active, short-lived active metabolites
–> alprazolam, triazolam (5-24 hours)
3) long-lived and active metabolites
–> rest of the benzo’s
describe age influence on metabolism of benzo’s
- in elderly, HEPATIC PROCESSING SLOWS FOR SOME RXNS
- INCREASE IN AGE:
–> decreased lean body mass
–> INCREASED Vd for many lipid soluble drugs
–> DECREASED RATE OF ELIMINATION
- DIAZEPAM is AGE DEPENDENT
- Oxazepam and lorazepam are AGE INDEPENDENT
describe mech of action of benzo’s
- Bind to GABAA receptors and potentiate effects (chloride channels)
–> INCREASE frequency of opening and conductase of Cl- channels
- bind to BZ sites between alpha 1 and gamma2
–> influx of chloride ion
–> increased membrane hyperpolarization and overall neuronal inhibition
–> potentiate GABAergic inhibition at ALL levels of the neuraxis
describe alpha 1 and alpha 2 functions
- Alpha 1 subunit = sedation, anticonvulsant action, anterograde amnesia
–> LEss sensitive to benzo (requires higher dose)
- Apha 2 subunit = anxiolysis
–> MORE SENSITIVE TO BENZO
describe side effects/toxicity of benzodiazepines
- Drowsiness and sedation
- Ataxia
- Respiratory depression = CAN BE LETHAL IF COMBINED WITH OTHER DEPRESSANTS
- Anterograde amnesia (Flunitrazepam)
- Tolerance (sedative effects) (more common in short acting agents) (prolonged use)
- Dependence (physical and psychological - addiction)
- WIthdrawal - abrupt cessation of drugs results in number of unpleasant symtpoms (opposite of drug effects.. increase anxiety)
describe contraindications
- pregnancy
- elderly
- substance abuse a concern
describe drug interactions of benzo
- ADDITIVE CNS DEPRESSION = ETHANOL, opioids, anticonvulsants, phenothiazine, antihistamines, tricyclinc antidepressants
