Barbiturates

1. MARIA FE SALVADOR NAVARRETE MD BIOLOGICAL THERAPIES

2. Barbiturates and Similarly Acting Drugs used as sedative-hypnotic agents in 20th century\ high abuse and addiction potential, a narrow therapeutic range with low therapeutic index , and unfavorable side effects . The use of barbiturates and similar compounds such as meprobamate ( Miltown ) has been practically eliminated by the benzodiazepines , buspirone ( BuSpar ), and hypnotics such as zolpidem ( Ambien ) and zaleplon (Sonata), which have a lower abuse potential and a higher therapeutic index than the barbiturates . the barbiturates and similarly acting drugs still have a role in the treatment of certain mental disorders.

3. Pharmacologic Actions well absorbed after oral administration. The binding of barbiturates to plasma proteins is high, but lipid solubility varies . metabolized by the liver and excreted by the kidneys. The half-lives of specific barbiturates range from 1 to 120 hours (Table 36.8-1). Barbiturates may also induce hepatic enzymes ( cytochrome P450), thereby reducing the levels of both the barbiturate and any other concurrently administered drugs metabolized by the liver . The mechanism of action of barbiturates involves the γ-aminobutyric acid (GABA) receptorâ €“benzodiazepine receptorâ €“chloride ion channel complex.

4. Therapeutic Indications: Electroconvulsive Therapy Methohexital ( Brevital ) is commonly used as an anesthetic agent for electroconvulsive therapy (ECT ). It has lower cardiac risks Used intravenously, methohexital produces rapid unconsciousness and, because of rapid redistribution, it has a brief duration of action (5 to 7 minutes ) Typical dosing for ECT is 0.7 to 1.2 mg/kg. Methohexital can also be used to abort prolonged seizures in ECT or to limit postictal agitation.

5. Seizures Phenobarbital ( Solfoton , Luminal), the most commonly used barbiturate for treatment of seizures, has indications for the treatment of generalized tonic- clonic and simple partial seizures . Parenteral barbiturates are used in the emergency management of seizures independent of cause. Intravenous (IV) phenobarbital should be administered slowly, 10 to 20 mg/kg for status epilepticus .

6. Narcoanalysis Amobarbital ( Amytal ) has been used historically as a diagnostic aid in a number of clinical conditions, including conversion reactions, catatonia, hysterical stupor, and unexplained muteness, and to differentiate stupor of depression, schizophrenia, and structural brain lesions.

7. SLEEP The barbiturates reduce sleep latency and the number of awakenings during sleep, although tolerance to these effects generally develops within 2 weeks . Discontinuation of barbiturates often leads to rebound increases on electroencephalogram (EEG) measures of sleep and a worsening of the insomnia.