Ser-Ap-Es (Hydralazine Hydrochloride / Hydrochlorothiazide / Reserpine) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Reserpine

MAO inhibitors should be avoided or used with extreme caution.

      Reserpine should be used cautiously with digitalis and quinidine, since cardiac arrhythmias have occurred with rauwolfia preparations.

      Concurrent use of tricyclic antidepressants may decrease the antihypertensive effect of reserpine (see CONTRAINDICATIONS).

      Concurrent use of reserpine and direct or indirect-acting sympathomimetics should be closely monitored. The action of direct-acting amines (epinephrine, isoproterenol, phenylephrine, metaraminol) may be prolonged when given to patients taking reserpine. The action of indirect-acting amines (ephedrine, tyramine, amphetamines) is inhibited.

Hydralazine

MAO inhibitors should be used with caution in patients receiving hydralazine. When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. Profound hypotensive episodes may occur when diazoxide injections and hydralazine are used concomitantly.

Hydrochlorothiazide

Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

      Hypokalemia may develop during concomitant use of steroids or ACTH.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged.

      Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

      Thiazides may increase the responsiveness to tubocurarine.

      Lithium renal clearance is reduced by thiazides, increasing the risk of lithium toxicity.

      There have been rare reports in the literature of hemolytic anemia occurring with the concomitant use of hydrochlorothiazide and methyldopa.

      Concurrent administration of some nonsteroidal anti-inflammatory agents may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics.

      Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

OVERDOSAGE

Acute Toxicity

No deaths due to acute poisoning with Ser-Ap-Es have been reported. Oral LD₅₀’s in animals (mg/kg): rats, 397; mice, 272.

Signs and Symptoms

Reserpine

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.

Hydralazine

Signs and symptoms of overdosage include hypotension, tachycardia, headache, and generalized skin flushing.

      Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia, and profound shock.

Hydrochlorothiazide

The most prominent feature of poisoning is acute loss of fluid and electrolytes.

Cardiovascular: Tachycardia, hypotension, shock.

Neuromuscular: Weakness, confusion, dizziness, cramps of the calf muscles. paresthesia, fatigue, impairment of consciousness.

Digestive: Nausea, vomiting, thirst.

Renal: Polyuria, oliguria, or anuria (due to hemoconcentration).

Laboratory Findings: Hypokalemia, hyponatremia, hypochloremia, alkalosis; increased BUN (especially in patients with renal insufficiency).

Combined Poisoning: Signs and symptoms may be aggravated or modified by concomitant intake of antihypertensive medication, barbiturates, digitalis (hypokalemia), corticosteroids, narcotics, or alcohol.

Treatment

There is no specific antidote.

      The gastric contents should be evacuated, taking adequate precautions against aspiration and for protection of the airway. An activated charcoal slurry may be instilled if conditions permit. Dialysis may not be effective for elimination of Ser-Ap-Es because of its plasma protein binding (see CLINICAL PHARMACOLOGY).

      These manipulations may have to be omitted or carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock.

      If hypotension or shock occurs, the patient's legs should be kept raised and lost fluid and electrolytes (potassium, sodium) should be replaced.

      Support of the cardiovascular system is of primary importance in suspected hydralazine overdosage. If possible, vasopressors should not be given, but if a vasopressor is required, care should be taken not to precipitate or aggravate cardiac arrhythmia. Tachycardia responds to beta blockers. Digitalization may be necessary.

      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 to treat the symptomatic effects of reserpine overdosage.

      Fluid and electrolyte balance (especially serum potassium) and renal function should be monitored until conditions become normal. Since reserpine is long-acting, the patient should be observed carefully for at least 72 hours.

CONTRAINDICATIONS

Reserpine

Hypersensitivity to reserpine; mental depression or history of mental depression (especially with suicidal tendencies); active peptic ulcer, ulcerative colitis; patients receiving electroconvulsive therapy.

Hydralazine

Hypersensitivity to hydralazine; coronary artery disease; mitral valvular rheumatic heart disease.

Hydrochlorothiazide

Anuria; hypersensitivity to this or other sulfonamide-derived drugs.