Anxiolytic & Hypnotic Drugs 6
Nonprescription antihistamines with sedating properties, such as diphenhydramine and doxylamine, are effective in treating mild types of insomnia. However, these drugs are usually ineffective for all but the milder forms of situational insomnia. Furthermore, they have numerous undesirable side effects (such as anticholinergic effects) that make them less useful than the benzodiazepines. These sedative antihistamines are marketed in numerous over-the-counter products. G. Ethanol Ethanol (ethyl alcohol) has anxiolytic and sedative effects, but its toxic potential outweighs its benefits. Alcoholism is a serious medical and social problem. Ethanol [ETH-an-ol] is a CNS depressant, producing sedation and, ultimately, hypnosis with increasing dosage. Ethanol has a shallow dose–response curve; therefore, sedation occurs over a wide dosage range. It is readily absorbed orally and has a volume of distribution close to that of total body water. Ethanol is metabolized primarily in the liver, first to acetaldehyde by alcohol dehydrogenase and then to acetate by aldehyde dehydrogenase .Elimination is mostly through the kidney, but a fraction is excreted through the lungs. Ethanol synergizes with many other sedative agents and can produce severe CNS depression with benzodiazepines, antihistamines, or barbiturates. Chronic consumption can lead to severe liver disease, gastritis, and nutritional deficiencies. Cardiomyopathy is also a consequence of heavy drinking. The treatment of choice for alcohol withdrawal are the benzodiazepines. Carbamazepine is effective in treating convulsive episodes during withdrawal. Metabolism of ethanol, and the effect of disulfiram. NAD+ = oxidized form of nicotinamideadenine dinucleotide; NADH = reduced form of nicotinamide-adenine dinucleotide. Disulfiram: Disulfiram [dye-SUL-fi-ram] blocks the oxidation of acetaldehyde to 1. acetic acid by inhibiting aldehyde dehydrogenase .This results in the accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea. Disulfiram has found some use in the patient seriously desiring to stop alcohol ingestion. A conditioned avoidance response is induced so that the patient abstains from alcohol to prevent the unpleasant effects of disulfiram-induced acetaldehyde accumulation. Naltrexone: Naltrexone [nal-TREX-own] is a long-acting opiate antagonist (available orally or as a long-acting injectable) that is U.S. Food and Drug Administration–approved for the treatment of alcohol dependence and should be utilized in conjunction with supportive psychotherapy. It is better tolerated than disulfiram and does not produce the aversive reaction that disulfiram does. 2. Acamprosate: An agent utilized in alcohol dependence treatment programs with an as yet poorly understood mechanism of action that should also be utilized in conjunction with supportive psychotherapy. <