amobarbital

amobarbital sodium
Amytal

Available forms
Available by prescription only
Capsules: 200 mg
Powder for injection: 250-mg, 500-mg vials
Tablets: 30 mg

Indications and dosages
 To produce sedation. Adults: Usually 30 to 50 mg P.O. b.i.d. or t.i.d. but may range from 15 to 120 mg b.i.d. to q.i.d.
Children: 2 mg/kg P.O. daily divided into four equal doses.
 To treat insomnia. Adults: 65 to 200 mg P.O. or deep I.M. h.s.; I.M. injection not to exceed 5 ml in any one site. Maximum dose is 500 mg.
Children older than age 6: 2 to 3 mg/kg deep I.M. h.s.
 To produce preanesthetic sedation. Adults: 200 mg P.O. 1 to 2 hours before surgery.
 To produce sedation during labor. Adults: 200 to 400 mg P.O.; may repeat at 1- to 3-hour intervals. Maximum dose is 1 g.
 To produce anticonvulsant effects. Adults: 65 to 500 mg by slow I.V. injection (rate not exceeding 100 mg/minute). Maximum dose is 1 g.

Pharmacodynamics
Anticonvulsant action: Exact cellular site and mechanism of action unknown. Parenteral amobarbital suppresses the spread of seizure activity produced by epileptogenic foci in the cortex, thalamus, and limbic systems by enhancing the effect of gamma-aminobutyric acid (GABA). Both presynaptic and postsynaptic excitability are decreased.
Sedative-hypnotic action: Acts throughout the CNS as a nonselective depressant with an intermediate onset and duration of action. Particularly sensitive to this drug is the mesencephalic reticular activating system, which controls CNS arousal. Drug decreases both presynaptic and postsynaptic membrane excitability by facilitating the action of GABA.

Pharmacokinetics
Absorption: Absorbed well after oral administration. Absorption after I.M. administration is 100%.
Distribution: Distributed well throughout body tissues and fluids.
Metabolism: Metabolized in the liver by oxidation to a tertiary alcohol.
Excretion: Less than 1% of dose is excreted unchanged in the urine; rest is excreted as metabolites. The half-life is biphasic, with a first phase half-life of about 40 minutes and a second phase of about 20 hours. Duration of action is 6 to 8 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to barbiturates and in those with bronchopneumonia, other severe pulmonary insufficiency, or porphyria.
  Use cautiously in patients with suicidal tendencies, acute or chronic pain, history of drug abuse, hepatic or renal impairment, or pulmonary or CV disease.

Interactions
Drug-drug. Antidepressants, antihistamines, MAO inhibitors, narcotics, sedative-hypnotics, tranquilizers: May add to or potentiate CNS and respiratory depressant effects of these drugs. Use together cautiously.
Corticosteroids, digitoxin, doxycycline, hormonal contraceptives and other estrogens, theophylline and other xanthines: Enhances hepatic metabolism of these drugs. Monitor patient carefully.
Disulfiram, MAO inhibitors, valproic acid: Decrease metabolism of amobarbital and increase toxicity. Monitor patient carefully.
Griseofulvin: Impairs effectiveness of griseofulvin. Use together cautiously.
Phenytoin: May cause unpredictable fluctuations in serum phenytoin level. Monitor phenytoin level.
Rifampin: May decrease amobarbital levels by increasing metabolism. Monitor patient for drug effect.
Warfarin, other oral anticoagulants: Enhances enzymatic degradation of anticoagulants. Increased dosages of anticoagulants may be needed.
Drug-food. Any food: Decreases absorption of drug. Give on empty stomach to enhance absorption.
Drug-lifestyle. Alcohol use: May add to or potentiate CNS and respiratory depressant effects. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, lethargy, hangover, paradoxical excitement, somnolence, syncope.
CV: bradycardia, hypotension
GI: nausea, vomiting.
Hematologic: exacerbation of porphyria.
Respiratory: respiratory depression, apnea.
Skin: rash; urticaria; Stevens-Johnson syndrome; pain, irritation, and sterile abscess at injection site.
Other: angioedema, physical and psychological dependence.

Effects on lab test results
• May increase ammonia level.

Overdose and treatment
Signs and symptoms of overdose include unsteady gait, slurred speech, sustained nystagmus, somnolence, confusion, respiratory depression, pulmonary edema, areflexia, and coma. Oliguria, jaundice, hypothermia, fever, and shock with tachycardia and hypotension may occur.
 Treatment of overdose aims to maintain and support ventilation and pulmonary function as needed; support cardiac function and circulation with vasopressors and I.V. fluids as needed. If patient is conscious with a functioning gag reflex and ingestion has been recent, induce emesis by administering ipecac syrup. Gastric lavage may be performed if a cuffed endotracheal tube is in place to prevent aspiration when emesis is inappropriate. Follow with activated charcoal. Measure fluid intake and output, vital signs, and laboratory parameters. Maintain body temperature. Assess cardiopulmonary status frequently for possible alterations. Monitor blood counts for potential adverse reactions.
 Alkalinization of urine may be helpful in removing amobarbital from the body; hemodialysis may be useful in severe overdose. Assess renal and hepatic laboratory studies to ensure adequate drug removal.

Special considerations
• Not commonly used as a sedative or aid to sleeping; barbiturates have been replaced by safer benzodiazepines for such use.
• Administer drug orally on an empty stomach to enhance absorption.
• Reconstitute powder for injection with sterile water for injection. Roll vial in hands; don’t shake. Use 2.5 or 5 ml (for 250 or 500 mg of amobarbital) to make 10% solution. For I.M. use, prepare 20% solution by using 1.25 or 2.5 ml of sterile water for injection.
• Administer reconstituted parenteral solution within 30 minutes after opening vial.
• Don’t administer solution that’s cloudy or forms a precipitate after 5 minutes of reconstitution.
• Administer I.V. dose at no more than 100 mg/ minute in adults or 60 mg/m²/minute in children to prevent possible hypotension and respiratory depression. Have emergency resuscitative equipment available.
• Administer I.M. dose deep into large muscle mass, giving no more than 5 ml in any one injection site. Sterile abscess or tissue damage may result from inadvertent superficial I.M. or S.C. injection.
• Administering full loading doses over short periods of time to treat status epilepticus may require ventilatory support in adults.
• Amobarbital may cause a false-positive phentolamine test.
• Physiologic effects of amobarbital may impair absorption of cyanocobalamin.
• Amobarbital may decrease serum bilirubin levels in neonates, epileptic patients, and patients with congenital nonhemolytic unconjugated hyperbilirubinemia.
• EEG patterns are altered, with a change in low-voltage, fast-activity; changes persist for a time after therapy is discontinued.
• Monitor PT carefully when patient on amobarbital starts or ends anticoagulant therapy. Anticoagulant dosage may need to be adjusted.
• Monitor patient for adverse effects.
Breast-feeding patients
• Drug appears in breast milk and may cause drowsiness in infant. If so, dosage adjustment or discontinuation of drug or breast-feeding may be needed. Use with caution.
Pediatric patients
• Safe use in children younger than age 6 hasn’t been established. Drug may cause paradoxical excitement in some children.
Geriatric patients
• Elderly patients usually need lower doses.
• Confusion, disorientation, and excitability may occur in elderly patients. Use cautiously.

Patient education
• Warn patient of possible physical or psychological dependence with prolonged use.
• Tell patient to avoid alcohol while taking drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use