Drugs Info e-Learning: Benzodiazepines Advantages & Disadvantages

Sunday, 17 June 2012

Benzodiazepines

Advantages

-higher therapeutic index

-relatively safe even if overdose

-have little effect on respiratory depression

-muscle relaxation (useful for spasm & back pain)

-can treat seizures (clonazepam)

Disadvantages

-interaction with alcohol

-long-lasting 'hangover' effects

-withdrawal symptoms

-development of TOLERANCE

Pharmacokinetics of Benzodiazepines

Pharmacokinetic properties determine the choice of drug for different clinical conditions

Absorption - BDZs are weak bases, mainly absorbed from duodenum

- given orally - well & rapidly absorbed

Distribution - most BDZs extensively protein bound (85%-95%)

- large volume of distribution VD - accumulation in body fat (high lipid solubility)

- increase lipid solubility > high rate of entry into CNS > faster onset

- all BDZ cross placenta

- detectable in breast milk > may exert depression effects on the CNS of lactating infants

Metabolism - Metabolism: BDZs undergo extensive metabolism - Oxidation either by N-dealkylation or hydroxylation

- mostly by CYP3A4 or CYP2C19

- conjugation (glucuronides)

- conversion to active/inactive metabolite is an important distinction

- some BDZs are prodrugs & require metabolism (clorazepate)

- many have active metabolites with t1/2 greater than parent drug (long duration of action)

Excretion - mostly via urine

- as metabolites (predominantly glucuronides)

Drugs Info e-Learning