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Chapter: Modern Medical Toxicology: Cardiovascular Poisons: Diurets, Antihypertensives and Antiarrhythmics

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Hydralazine - Sympatholytic Drug Cardiovascular Poison

Hydralazine causes direct relaxation of arteriolar smooth muscle, but is not a dilator of capacitance vessels such as the coronary arteries.

Hydralazine

Hydralazine causes direct relaxation of arteriolar smooth muscle, but is not a dilator of capacitance vessels such as the coronary arteries. Because of preferential dilatation of arterioles over veins, postural hypotension is not a significant problem. Hydralazine is usually combined with a sympatholytic agent or a diuretic and is effective orally. Parenteral use is recommended for the treatment of hypertensive emergencies in pregnancy.

Toxicokinetics

About 50 to 90% bioavailability; peaks in plasma in about 1 hour; protein binding is about 88 to 90%; volume of distribution is 1.6 L/kg; metabolised by hydroxylation, followed by glucu-ronidation and N-acetylation; 3 to 14% is excreted unchanged in the urine; elimination half-life is about 2 to 8 hours.

Adverse Effects

·      Pharmacological: headache, dizziness, lacrimation, blurredvision, oedema of the eyelids, nausea, flushing, hypoten-sion, palpitations, and tachycardia. Myocardial ischaemia is not unlikely.

·      Immunological: lupus syndrome, serum sickness, glomeru-lonephritis. About 10 to 20% of patients on long-term hydralazine therapy with doses exceeding 400 mg daily develop a lupus-like syndrome. The syndrome occurs most commonly in Caucasians who are slow acetylators. Peripheral neuropathies have also been noted following chronic hydralazine therapy.

Clinical (Toxic) Features

·              Dizziness, syncope, palpitations and nausea.

Treatment

·              Decontamination, followed by IV fluid boluses, and peripher-ally acting vasopressors such as noradrenaline.** Calcium channel blockers or beta blockers may be considered in patients with persistent tachycardia or myocardial ischaemia. Peripheral neuropathies may be corrected with pyridoxine.

 

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