GABA-A enhancement giving anxiolysis, sedation, anticonvulsant and muscle relaxant effects
Expansion
Mechanism: positive allosteric modulation of the GABA-A receptor, increasing the frequency of chloride channel opening. They require endogenous GABA to work, which is why they have a ceiling effect and are safer in overdose than barbiturates, which increase channel opening duration and can act without GABA.
Effects: anxiolysis, sedation, anticonvulsant, muscle relaxation, and anterograde amnesia.
Choosing an agent by duration
- Short acting (midazolam, lorazepam): procedural sedation, status epilepticus
- Long acting (diazepam, chlordiazepoxide): alcohol withdrawal, where the long half-life gives a self-tapering effect
- Lorazepam is preferred in liver impairment and the elderly, since it undergoes glucuronidation only, with no active metabolites
Hazards: respiratory depression, especially with opioids or alcohol; falls and confusion in the elderly; tolerance and dependence within weeks; and a withdrawal syndrome that includes seizures and is potentially fatal, requiring a slow taper.
Flumazenil reverses them but is rarely used, since it can precipitate seizures in mixed overdose and in dependence.
Z drugs (zopiclone, zolpidem) act at the same receptor and carry the same dependence and falls risk.