Ismelin (Guanethidine Monosulfate) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

Concurrent use of Ismelin and rauwolfia derivatives may cause excessive postural hypotension, bradycardia, and mental depression.

Both digitalis and Ismelin slow the heart rate.

Thiazide diuretics enhance the antihypertensive action of Ismelin (see DOSAGE AND ADMINISTRATION).

Amphetamine-like compounds, stimulants (e. g., ephedrine, methylphenidate), tricyclic antidepressants (e.g., amitriptyline, imipramine, desipramine) and other psychopharmacologic agents (e.g., phenothiazines and related compounds), as well as oral contraceptives, may reduce the hypotensive effect of Ismelin.

MAO inhibitors should be discontinued for at least 1 week before starting therapy with Ismelin.

OVERDOSAGE

Acute Toxicity

No deaths due to acute poisoning have been reported.

Oral LD₅₀ in rats: 1262 mg/kg.

Signs and Symptoms

Postural hypotension (with dizziness, blurred vision, and possibly syncope when standing), shock, and bradycardia are most likely to occur; diarrhea (possibly severe), nausea, and vomiting may also occur. Unconsciousness is unlikely if adequate blood pressure and cerebral perfusion can be maintained by placing the patient in the supine position and by administering other treatment as required.

Treatment

There is no specific antidote.

Treatment should consist of gastric lavage. An activated charcoal slurry should be instilled and laxatives given, if conditions permit.

In sinus bradycardia, atropine should be administered.

In previously normotensive patients, treatment has consisted essentially of restoring blood pressure and heart rate to normal by keeping the patient in the supine position. Normal homeostatic control usually returns gradually over a 72-hour period in these patients.

In previously hypertensive patients, particularly those with impaired cardiac reserve or other cardiovascular- renal disease, intensive treatment may be required to support vital functions and to control cardiac irregularities that might be present. The supine position must be maintained; if vasopressors are required, they must be used with extreme caution, since Ismelin may increase responsiveness, causing a rise in blood pressure and development of cardiac arrhythmias.

Diarrhea, if severe or persistent, should be treated with anticholinergic agents to reduce intestinal hypermotility; hydration and electrolyte balance should be maintained.

Since Ismelin is excreted slowly, cardiovascular and renal function should be monitored for a few days.

CONTRAINDICATIONS

Known or suspected pheochromocytoma; hypersensitivity; frank congestive heart failure not due to hypertension; use of monoamine oxidase (MAO) inhibitors.