Kaplan + Sadock's Synopsis of Psychiatry, 11e

946

Chapter 29: Psychopharmacological Treatment

tion must be exercised when prescribing barbiturates to patients who are taking other drugs that are metabolized in the liver, especially cardiac drugs and anticonvulsants. Because indi- vidual patients have a wide range of sensitivities to barbitu- rate-induced enzyme induction, it is not possible to predict the degree to which the metabolism of concurrently administered medications may be affected. Drugs that have their metabolism enhanced by barbiturate administration include opioids, antiar- rhythmic agents, antibiotics, anticoagulants, anticonvulsants, antidepressants, b -adrenergic receptor antagonists, dopamine receptor antagonists, contraceptives, and immunosuppressants. Laboratory Interferences No known laboratory interferences are associated with the administration of barbiturates. Dose and Clinical Guidelines Barbiturates and other drugs described later begin to act within 1 to 2 hours of administration. The doses of barbiturates vary, and treatment should begin with low doses that are increased to achieve a clinical effect. Children and older people are more sensitive to the effects of the barbiturates than are young adults. The most commonly used barbiturates are available in a variety of dose forms. Barbiturates with half-lives in the 15- to 40-hour range are preferable, because long-acting drugs tend to accumu- late in the body. Clinicians should instruct patients clearly about the adverse effects and the potential for dependence associated with barbiturates. Although determining plasma concentrations of barbiturates is rarely necessary in psychiatry, monitoring of phenobarbital concentrations is standard practice when the drug is used as an anticonvulsant. The therapeutic blood concentrations for pheno- barbital in this indication range from 15 to 40 mg/L, although some patients may experience significant adverse effects in that range. Barbiturates are contained in combination products with which the clinician should be familiar. Other Similarly Acting Drugs A number of agents that act similarly to the barbiturates have been used in the treatment of anxiety and insomnia. Three such available drugs are paraldehyde (Paral), meprobamate, and chloral hydrate (Noctec). These drugs are rarely used because of their abuse potential and potential toxic effects. Paraldehyde Paraldehyde is a cyclic ether and was first used in 1882 as a hyp- notic. It has also been used to treat epilepsy, alcohol withdrawal symptoms, and delirium tremens. Because of its low therapeutic index, it has been supplanted by the benzodiazepines and other anticonvulsants. Pharmacologic Actions.  Paraldehyde is rapidly absorbed from the gastrointestinal (GI) tract and from intramuscular (IM) injections. It is primarily metabolized to acetaldehyde by the liver, and unmetabolized drug is expired by the lungs. Reported

2 hours, up to three times (maximum, 500 mg over 6 hours). The amount needed for mild intoxication corresponds to the approx- imate daily dose of barbiturate used. Phenobarbital (30 mg) may then be substituted for each 100 mg of pentobarbital. This daily dose requirement can be administered in divided doses and gradually tapered by 10 percent a day, with adjustments made according to withdrawal signs. Precautions and Adverse Reactions Some adverse effects of barbiturates are similar to those of ben- zodiazepines, including paradoxical dysphoria, hyperactivity, and cognitive disorganization. Rare adverse effects associated with barbiturate use include the development of Stevens– Johnson syndrome, megaloblastic anemia, and neutropenia. Prior to the advent of benzodiazepines, the widespread use of barbiturates as hypnotics and anxiolytics made them the most common cause of acute porphyria reactions. Severe attacks of porphyria have decreased largely because barbiturates are now seldom used and are contraindicated in patients with the disease. A major difference between the barbiturates and the benzo- diazepines is the low therapeutic index of the barbiturates. An overdose of barbiturates can easily prove fatal. In addition to narrow therapeutic indexes, the barbiturates are associated with a significant risk of abuse potential and the development of tol- erance and dependence. Barbiturate intoxication is manifested by confusion, drowsiness, irritability, hyporeflexia or areflexia, ataxia, and nystagmus. The symptoms of barbiturate withdrawal are similar to, but more marked than, those of benzodiazepine withdrawal. Ten times the daily dose or 1 g of most barbiturates causes severe toxicity; 2–10 g generally proves fatal. Manifestations of barbiturate intoxication may include delirium, confusion, excitement, headache, and central nervous system (CNS) and respiratory depression, ranging from somnolence to coma. Other adverse reactions include Cheyne–Stokes respiration, shock, miosis, oliguria, tachycardia, hypotension, hypothermia, irritability, hyporeflexia or areflexia, ataxia, and nystagmus. Treatment of overdose includes induction of emesis or lavage, activated charcoal, and saline cathartics; supportive treatment, including maintaining airway and respiration and treating shock as needed; maintaining vital signs and fluid balance; alkaliniz- ing the urine, which increases excretion; forced diuresis if renal function is normal, or hemodialysis in severe cases. Because of some evidence of teratogenicity, barbiturates should not be used by pregnant women or women who are breastfeeding. Barbiturates should be used with caution by patients with a history of substance abuse, depression, diabetes, hepatic impairment, renal disease, severe anemia, pain, hyper- thyroidism, or hypoadrenalism. Barbiturates are also contrain- dicated in patients with acute intermittent porphyria, impaired respiratory drive, or limited respiratory reserve. Drug Interactions The primary area for concern about drug interactions is the potentially dangerous effects of respiratory depression. Barbi- turates should be used with great caution with other prescribed CNS drugs (including antipsychotic and antidepressant drugs) and nonprescribed CNS agents (e.g., alcohol). In addition, cau-