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CARDIOVASCULAR SYSTEM › ANTIHYPERTENSIVES › ANTIHYPERTENSIVES AND DIURETICS IN COMBINATION › MAO inhibitors and diuretics
pargyline and diuretics
C02LL01
Forms & Strengths
- Combination formulations historically included pargyline hydrochloride combined with thiazide diuretics (e.g., methyclothiazide).
- Availability is extremely limited or withdrawn in many markets due to severe safety risks associated with irreversible MAOIs.
Adult Dosing
- Hypertension: Historically initiated at low doses (e.g., pargyline 10-25 mg daily combined with methyclothiazide 2.5-5 mg) and titrated cautiously based on blood pressure response.
- Maximum doses were strictly limited to avoid severe hypertensive crises and orthostatic hypotension.
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established; use in children is contraindicated.
Indications
- Management of moderate to severe hypertension, particularly cases refractory to single-agent therapy.
- Largely obsolete in modern clinical practice due to safer and more effective antihypertensive regimens.
Mechanism of Action
- Pargyline: Irreversible, non-selective monoamine oxidase inhibitor (MAOI) that increases tissue concentrations of biogenic amines (norepinephrine, dopamine, serotonin).
- Diuretic (e.g., methyclothiazide): Inhibits sodium reabsorption in the distal renal tubules, leading to increased excretion of sodium and water, reducing blood volume and peripheral vascular resistance.
Contraindications
- Concomitant use of sympathomimetic drugs, tyramine-rich foods, other antidepressants (SSRIs, TCAs, other MAOIs), and CNS depressants.
- Pheochromocytoma, congestive heart failure, severe renal impairment, and severe hepatic disease.
- History of cerebrovascular disease or severe cardiovascular disease.
Adverse Reactions
- Hypertensive crisis triggered by tyramine-containing foods or sympathomimetics.
- Severe orthostatic hypotension, dizziness, and syncope.
- Electrolyte imbalances (hypokalemia, hyponatremia) and hyperuricemia secondary to the diuretic component.
- Central nervous system effects including excitation, insomnia, and dry mouth.
Drug Interactions
- Sympathomimetics (e.g., pseudoephedrine, epinephrine) can cause severe, potentially fatal hypertensive crises.
- Other antidepressants (SSRIs, SNRIs, TCAs) risk serotonin syndrome or severe hypertensive reactions.
- Antihypertensive agents and anesthetics can result in profound additive hypotension.
- Tyramine-rich foods (aged cheeses, cured meats, fermented products) can precipitate acute hypertensive crisis.
Curated Content: Needs Vetting Before Put to Clinical Use