Depressants Clomethiazole

Clomethiazole, like the benzodiazepines, has an additive effect with other CNS depressants, and can cause profound bradycardia when combined with beta-adreno-ceptor antagonists. 

Chloral hydrate, clomethiazole and barbiturates also enhance GABA function but at high doses have the additional capacity directly to open the membrane chloride channel (see Figure 19.4) this may lead to potentially lethal respiratory depression and explains their low therapeutic ratio. These drugs also have a propensity for abuse/misuse and are very much second-line treatments. 

Clomethiazole was an alternative to a benzodiazepine for alcohol withdrawal but is now rarely used due to concerns over respiratory depression and abuse potential. 

Clomethiazole has been successfully used to treat alcohol withdrawal, but the long-term use of alcohol with clomethiazole can cause serious, even potentially fatal CNS depression, due to additive CNS depressant effects fatal respiratory depression can occur even with short-term use in alcoholics with cirrhosis. The concurrent use of clomethiazole and alcohol may also affect driving skills. Clomethiazole bioavailability may be increased by alcohol. 

Alcoholics readily transfer dependency to clomethiazole and may visit several practitioners and hospitals to get their supplies. Tolerance develops so that very large amounts may need to be taken (up to 25 g daily). Often alcohol abuse continues and the combination of large amounts of alcohol and clomethiazole can result in coma and even fatal respiratory depression, due mainly to simple additive CNS depression. ... 

Clomethiazole should not be given long-term for alcohol withdrawal states or to those who continue to drink alcohol. Use for more than 9 days is not recommended. It has been said that if prescribers choose to manage detoxification at home, it should be done under very close supervision, issuing prescriptions for only one day s supply to ensure daily contact and to minimise tiie risk of abuse. And if the patient shows evidence of tolerance or clomethiazole dependency or of continuing to drink alcohol, the only safe policy is rapid admission for inpatient care. The manufacturer warns that alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short-term use. ... 

Clomethiazole and diazoxide, given to pregnant women in labour, can cause marked respiratory depression in their infants for up to 36 hours after birth. 

Clomethiazole has some respiratory depressant effeets, and is eontraindi-eated in patients with respiratory deficiency, but it is not clear why, having passed across the plaeenta into the foetus, its effeets should apparently be so markedly inereased by diazoxide. 

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