Reserpine (Reserpine) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal Tumorigenicity

Rodent studies have shown that reserpine is an animal tumorigen, causing an increased incidence of mammary fibroadenomas in female mice, malignant tumors of the seminal vesicles in male mice, and malignant adrenal medullary tumors in male rats. These findings arose in 2-year studies in which the drug was administered in the feed at concentrations of 5 to 10 ppm-about 100 to 300 times the usual human dose. The breast neoplasms are thought to be related to reserpine’s prolactin-elevating effect. Several other prolactin-elevating drugs have also been associated with an increased incidence of mammary neoplasia in rodents.

The extent to which these findings indicate a risk to humans is uncertain. Tissue culture experiments show that about one third of human breast tumors are prolactin-dependent in vitro, a factor of considerable importance if the use of the drug is contemplated in a patient with previously detected breast cancer. The possibility of an increased risk of breast cancer in reserpine users has been studied extensively; however, no firm conclusion has emerged. Although a few epidemiologic studies have suggested a slightly increased risk (less than twofold in all studies except one) in women who have used reserpine, other studies of generally similar design have not confirmed this. Epidemiologic studies conducted using other drugs (neuroleptic agents) that, like reserpine, increase prolactin levels and therefore would be considered rodent mammary carcinogens have not shown an association between chronic administration of the drug and human mammary tumorigenesis. While long-term clinical observation has not suggested such as association, the available evidence is considered too limited to be conclusive at this time. An association of reserpine intake with pheochromocytoma or tumors of the seminal vesicles has not been explored.

OVERDOSAGE

Acute toxicity

No deaths due to acute poisoning with reserpine have been reported.

Highest known doses survived: children, 1000 mg (age and sex not specified); young children, 200 mg (20-month-old boy).

Oral LD₅₀'s in animals (mg/kg): rat, 2993; mouse, 47 and 500.

Signs and Symptoms

The clinical picture of acute poisoning is characterized chiefly by signs and symptoms due to the reflex parasympathomimetic effect of reserpine.

Impairment of consciousness may occur and may range from drowsiness to coma, depending upon the severity of overdosage. Flushing of the skin, conjunctival injection, and pupillary constriction are to be expected. Hypotension, hypothermia, central respiratory depression, and bradycardia may develop in cases of severe overdosage. Increased salivary and gastric secretion and diarrhea may also occur.

Treatment

There is no specific antidote.

Stomach contents should be evacuated, taking adequate precautions against aspiration and for protection of the airway. Activated charcoal slurry should be instilled.

The effects of reserpine overdosage should be treated symptomatically. If hypotension is severe enough to require treatment with a vasopressor, one having a direct action upon vascular smooth muscle (e.g., phenylephrine, levarterenol, metaraminol) should be used. Since reserpine is long-acting, the patient should be observed carefully for at least 72 hours, and treatment administered as required.

CONTRAINDICATIONS

Known hypersensitivity, mental depression or history of mental depression (especially with suicidal tendencies), active peptic ulcer, ulcerative colitis, and patients receiving electroconvulsive therapy.