The Massachusetts General Hospital Handbook of Neurology

2017-07-07 02:10:07

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

> Table of Contents > Drugs > Benzodiazepines

Benzodiazepines

A. Indications

Anxiolysis, sedation, muscle spasms, seizures.

B. Time course

Diazepam has the shortest onset; oxazepam the shortest duration. Short-acting drugs, e.g., alprazolam, can cause rebound anxiety.

C. Mechanism

Benzodiazepines are GABA-A receptor agonists.

D. Side effects

Respiratory depression, hypotension. Mildly teratogenic during first trimester only. Although shorter acting ones, e.g., alprazolam,

P.166

are less sedating, they cause more rebound and withdrawal. Do not use them as analgesics; they can worsen pain.

Withdrawal: Can occur after prolonged use, so taper slowly. Sx are similar to alcohol withdrawal and can be life threatening.

Overdose: Flumazenil partly reverses effects but probably not the respiratory depression, and it may trigger seizures. Try 0.2 mg (2 mL) IV over 30 sec, then 0.3 mg q min to effect, max. of 3 mg (10 doses). Since half-life is 15 min-2.5 h, consider IV drip of 1 mg/h.

Table 46. Benzodiazepine half-life and metabolism.

Generic Name	Brand Name	Half-Life	PO Dose (mg)	Liver Metab?
Alprazolam	Xanax	12 h	0.25-0.5 tid
Clonazepam	Klonopin	18-48 h	0.25-2 tid	Yes
Chlordiazepoxide	Librium	24 h	5-25 tid/qid	Yes
Diazepam	Valium	20-80 h	2-10 bid/qid	Yes
Lorazepam	Ativan	8-20 h	0.5-2 q6-8h
Oxazepam	Serax	8 h	10-15 tid/qid

E. Comorbid dz

Liver failure: In cirrhotics and the elderly, benzodiazepines metabolized in the liver (e.g., diazepam) can linger for weeks. Lorazepam or oxazepam, metabolized primarily in the kidney, are preferred. If pt has hepatic encephalopathy, avoid benzodiazepines completely; use narcotics if sedation is required.

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