Generic Name

Hydralazine

Mechanism

• Smooth‑muscle relaxation in arterioles via endothelial‑independent mechanisms.
• Inhibits calcium influx into vascular smooth‑muscle cells, reducing intracellular calcium and decreasing membrane potential.
• Promotes nitric‑oxide–mediated phosphodiesterase inhibition, increasing cGMP and promoting vasodilation.
• Results in decreased peripheral vascular resistance, lowering mean arterial pressure (MAP).

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration 30‑60 min after dosing.
• Distribution: High protein binding (~90 % albumin), wide tissue distribution.
• Metabolism: Hepatic conjugation via glucuronidation; minimal CYP450 involvement.
• Elimination: Renal excretion of metabolites; half‑life ~3–4 h (oral); longer (~10 h) intramuscular.
• Drug interactions: Inhibits digoxin efflux by P‑gp, increasing serum digoxin; caution with MAO‑I (serotonin syndrome risk).

Indications

• Primary hypertension (single agent or combination).
• Refractory heart failure: Added to ACEI/ARB/β‑blocker background, particularly in NYHA III–IV disease.
• Hypertensive emergency: IV formulation for rapid BP control when other agents are unsuitable.

Contraindications

• Contraindications:
• Known hypersensitivity to hydralazine or the benzothiadiazine class.
• Severe aortic stenosis or isolated systolic hypertension in the elderly (risk of orthostatic hypotension).
• Warnings:
• Drug-induced lupus erythematosus (DILE) – occurs after extended use (>12 weeks).
• Serotonergic syndrome: avoid use with MAO inhibitors, SSRIs, SNRIs, tramadol.
• Beta‑blocker additive effect: careful in asthma or chronic obstructive pulmonary disease (COPD).
• Precautions: Monitor renal function; adjust dose in severe renal impairment.

Dosing

• Begin low, titrate slowly to mitigate hypotension and tachycardia.
• Divide total daily dose into multiple (3–4) doses for steady BP control.

Adverse Effects

Common:
• Flushing and warmth (20–30 %).
• Headache, dizziness, light‑headedness.
• Tachycardia (especially 24‑hour IV).
• Nausea and abdominal discomfort.

Serious/High‑Yield:
• Drug‑induced lupus (antibodies anti‑dsDNA, antihistone; cutaneous rash, photosensitivity, arthralgias).
• Serotonin syndrome (hypertension, hyperthermia, agitation; when combined with serotonergic agents).
• Allergic reactions (anaphylaxis rare).
• Renal dysfunction (rare, due to vasoconstriction).

Monitoring

• Blood pressure: at each visit; consider ambulatory BP if labile.
• Heart rate: watch for reflex tachycardia.
• Kidney function: serum creatinine & BUN baseline, then every 4–6 weeks during titration.
• Liver enzymes: routine in long‑term therapy.
• Autoimmune workup: anti‑dsDNA, antihistone if DILE suspected.
• Digoxin levels: if co‑administered, monitor serum digoxin concentration (target 0.5–0.9 ng/mL).

Clinical Pearls

• DILE Surveillance: Stop hydralazine if rash develops; auto‑antibody panel can confirm diagnosis.
• IV Hydralazine “Push”: Administer slowly over 5 min to avoid sudden hypotension and reflex tachycardia.
• Heart Failure Combo: Add hydralazine‑isosorbide dinitrate (H–I) in African‑American patients with advanced HF per CHART‑I trial; monitor for flushing and headaches.
• Digoxin Interaction: Hydralazine reduces digoxin clearance; start at half the usual dose and titrate while checking levels.
• Contraindicated with MAO‑Is: Hydralazine + MAO‑I → risk of serotonin syndrome; avoid and counsel patients on serotonergic OTC drugs.
• Patient Education: Encourage upright positional changes slowly; advise on signs of hypotension (dizziness, fainting).

Key take‑away: Hydralazine remains a valuable but underused agent in tailored antihypertensive regimens and advanced heart failure therapy. Proper titration, vigilance for lupus, and awareness of drug interactions are essential for safe use.