Seconal (Secobarbital Sodium) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions

Most reports of clinically significant drug interactions occurring with the barbiturates have involved phenobarbital. However, the application of these data to other barbiturates appears valid and warrants serial blood level determinations of the relevant drugs when there are multiple therapies.

1. Anticoagulants —Phenobarbital lowers the plasma levels of dicumarol and causes a decrease in anticoagulant activity as measured by the prothrombin time. Barbiturates can induce hepatic microsomal enzymes, resulting in increased metabolism and decreased anticoagulant response of oral anticoagulants (eg, warfarin, acenocoumarol, dicumarol, and phenprocoumon). Patients stabilized on anticoagulant therapy may require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen.

2. Corticosteroids —Barbiturates appear to enhance the metabolism of exogenous corticosteroids, probably through the induction of hepatic microsomal enzymes. Patients stabilized on corticosteroid therapy may require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen.

3. Griseofulvin —Phenobarbital appears to interfere with the absorption of orally administered griseofulvin, thus decreasing its blood level. The effect of the resultant decreased blood levels of griseofulvin on therapeutic response has not been established. However, it would be preferable to avoid concomitant administration of these drugs.

4. Doxycycline —Phenobarbital has been shown to shorten the half-life of doxycycline for as long as 2 weeks after barbiturate therapy is discontinued.

This mechanism is probably through the induction of hepatic microsomal enzymes that metabolize the antibiotic. If barbiturates and doxycycline are administered concurrently, the clinical response to doxycycline should be monitored closely.

5. Phenytoin, Sodium Valproate, Valproic Acid —The effect of barbiturates on the metabolism of phenytoin appears to be variable. Some investigators report an accelerating effect, whereas others report no effect. Because the effect of barbiturates on the metabolism of phenytoin is not predictable, phenytoin and barbiturate blood levels should be monitored more frequently if these drugs are given concurrently. Sodium valproate and valproic acid increase the secobarbital sodium serum levels; therefore, secobarbital sodium blood levels should be monitored closely and appropriate dosage adjustments made as clinically indicated.

6. CNS Depressants —The concomitant use of other CNS depressants, including other sedatives or hypnotics, antihistamines, tranquilizers, or alcohol, may produce additive depressant effects.

7. Monoamine Oxidase Inhibitors (MAOIs)—MAOIs prolong the effects of barbiturates, probably because metabolism of the barbiturate is inhibited.

8. Estradiol, Estrone, Progesterone, and Other Steroidal Hormones —Pretreatment with or concurrent administration of phenobarbital may decrease the effect of estradiol by increasing its metabolism. There have been reports of patients treated with antiepileptic drugs (eg, phenobarbital) who become pregnant while taking oral contraceptives. An alternate contraceptive method might be suggested to women taking barbiturates.

OVERDOSAGE

The toxic dose of barbiturates varies considerably. In general, an oral dose of 1 g of most barbiturates produces serious poisoning in an adult. Death commonly occurs after 2 to 10 g of ingested barbiturate. The sedated, therapeutic blood levels of secobarbital range between 0.5 to 5 mcg/mL; the usual lethal blood level ranges from 15 to 40 mcg/mL. Barbiturate intoxication may be confused with alcoholism, bromide intoxication, and various neurologic disorders. Potential tolerance must be considered when evaluating significance of dose and plasma concentration.

Signs and Symptoms —Symptoms of oral overdose may occur within 15 minutes and begin with central nervous system depression, underventilation, hypotension, and hypothermia, which may progress to pulmonary edema and death. Hemorrhagic blisters may develop, especially at pressure points.

In extreme overdose, all electrical activity in the brain may cease, in which case a “flat” EEG normally equated with clinical death cannot be accepted as indicative of brain death. This effect is fully reversible unless hypoxic damage occurs. Consideration should be given to the possibility of barbiturate intoxication even in situations that appear to involve trauma.

Complications such as pneumonia, pulmonary edema, cardiac arrhythmias, congestive heart failure, and renal failure may occur. Uremia may increase CNS sensitivity to barbiturates if renal function is impaired. Differential diagnosis should include hypoglycemia, head trauma, cerebrovascular accidents, convulsive states, and diabetic coma.

Treatment —To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.

Diuresis and peritoneal dialysis are of little value; hemodialysis and hemoperfusion enhance drug clearance and should be considered in serious poisoning. If the patient has chronically abused sedatives, withdrawal reactions may be manifest following acute overdose.

CONTRAINDICATIONS

Seconal Sodium is contraindicated in patients who are hypersensitive to barbiturates. It is also contraindicated in patients with a history of manifest or latent porphyria, marked impairment of liver function, or respiratory disease in which dyspnea or obstruction is evident.