Barbiturates and Similarly Acting Drugs



Barbiturates and Similarly Acting Drugs




For a more detailed discussion of this topic, see Barbiturates and Similarly Acting Substances, Sec. 31.9 p. 3038 in Comprehensive Textbook of Psychiatry, 9th Edition.



The first barbiturate to be used in medicine was barbital (Veronal), which was introduced in 1903. It was followed by phenobarbital (Luminal), amobarbital (Amytal), pentobarbital (Nembutal), secobarbital (Seconal), and thiopental (Pentothal). Many more have been synthesized, but only a handful has been used clinically (Table 7-1). Many problems are associated with these drugs, including 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 and hypnotics such as zolpidem (Ambien), eszopiclone (Lunesta) and zaleplon (Sonata), which have a lower abuse potential and a higher therapeutic index than the barbiturates. Nevertheless, the barbiturates still have an important role in the treatment of certain mental and convulsive disorders.


Pharmacologic Actions

The barbiturates are well absorbed after oral administration. The binding of barbiturates to plasma proteins is high, but lipid solubility varies. The individual barbiturates are metabolized by the liver and excreted by the kidneys. The half-lives of specific barbiturates range from 1 to 120 hours. The 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) receptor–benzodiazepine receptor–chloride ion channel complex.


Therapeutic Indications


Electroconvulsive Therapy

Methohexital (Brevital) is commonly used as an anesthetic agent for electroconvulsive therapy (ECT). It has lower cardiac risks than other barbiturate anesthetics. Used intravenously (IV), methohexital produces rapid unconsciousness, and because of its 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.









Table 7-1 Barbiturate Dosages (Adult)


















































































Drug Trade Name Available Preparations Hypnotic Dose Range Anticonvulsant Dose Range
Amobarbital Amytal 200 mg 50–300 mg 65–500 mg IV
Aprobarbital Alurate 40-mg/5-mL elixir 40–120 mg Not established
Butabarbital Butisol 15-, 30-, and 50-mg tablets 30-mg/5-mL elixir 45–120 mg Not established
Mephobarbital Mebaral 32-, 50-, and 100-mg tablets 100–200 mg 200–600 mg
Methohexital Brevital 500 mg/50 cc 1 mg/kg for electroconvulsive therapy Not established
Pentobarbital Nembutal 50- and 100-mg capsules 100–200 mg 100 mg IV, each minute up to 500 mg
    50-mg/mL injection or elixir    
    30-, 60-, 120-, and 200-mg suppository    
Phenobarbital Luminal Tablets range from 15–100 mg 30–150 mg 100–300 mg IV, up to 600 mg/day
    20-mg/5-mL elixir    
    30- to 130-mg/mL injection    
Secobarbital Seconal 100-mg capsule, 50-mg/mL injection 100 mg 5.5 mg/kg IV
IV, intravenous.


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. IV phenobarbital should be administered slowly at 10 to 20 mg/kg for status epilepticus.


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.

The Amytal interview is performed by placing the patient in a reclining position and administering amobarbital IV at 50 mg a minute. Infusion is continued until lateral nystagmus is sustained or drowsiness is noted, usually at 75 to 150 mg. After this, 25 to 50 mg can be administered every 5 minutes to maintain narcosis. The patient should be allowed to rest for 15 to 30 minutes after the interview before attempting to walk.


Because of the rise in laryngospasm, with IV amobarbital diazepam has become the drug of choice for narcoanyalysis.

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Jun 8, 2016 | Posted by in PSYCHIATRY | Comments Off on Barbiturates and Similarly Acting Drugs

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