Sunday November 8, 2009


Q: Which medicine may transiently reverse hepatic encephelopathy?

Answer: flumazenil

GABA is a neuroinhibitory substance produced in the gastrointestinal tract. Of all brain nerve endings, 24-45% may be GABAergic. Increased GABAergic tone is observed in patients with cirrhosis, perhaps because of decreased hepatic metabolism of GABA.

When GABA crosses the extrapermeable blood-brain barrier of patients with cirrhosis, it interacts with supersensitive postsynaptic GABA receptors. The GABA receptor, in conjunction with receptors for benzodiazepines and barbiturates, regulates a chloride ionophore. Binding of GABA to its receptor permits an influx of chloride ions into the postsynaptic neuron, leading to the generation of an inhibitory postsynaptic potential. Administration of benzodiazepines and barbiturates to patients with cirrhosis increases GABAergic tone and predisposes to depressed consciousness.

The GABA hypothesis is supported by the clinical observation that flumazenil, a benzodiazepine antagonist, can transiently reverse hepatic encephalopathy in patients with cirrhosis.