Hydralazine syndrome

This leaves hydralazine as the only drug of this kind available to date on the U.S. market for chronic use. The total picture of the mechanism of action of hydralazine is still not clearly defined but there is general agreement that direct relaxation of the vasculature leading to reduced peripheral resistance is the principal component of its mechanism of action. This drug has stood the test of time despite such side effects as headache, tachycardia and a syndrome which resembles acute systemic lupus erythematosus, often called "hydralazine syndrome" (1). 

Alarcon-Segoria D, Wakins KG, Worthington JW (1967) Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Medicine (Baltimore) 46 1-33... 

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

Direct Vasodilators Isosorbide dinitrate 20 mg and hydralazine 37.5 (BiDil) 1-2 tablets three times a day Minoxidil (Loniten) Hydralazine Heart failure (isosorbide dinitrate + hydralazine in African-Americans) A-HeFT66 Edema (minoxidil) Tachycardia Lupus-like syndrome (hydralazine) ... 

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. 

V-Acetylation /V-acetyl transferase Hydralazine (antihypertensive) Lupus erythematosus-like syndrome... 

Hydralazine Causes nitric oxide release Vasodilation reduce vascular resistance arterioles more sensitive than veins reflex tachycardia Hypertension minoxidil also used to treat hair loss Oral Toxicity Angina, tachycardia Hydralazine Lupus-like syndrome... 

Arteriolar dilators Probably increases NO synthesis in endothelium (see Chapter 11) Reduces blood pressure and afterload results in increased cardiac output Hydralazine plus nitrates have reduced mortality Oral 8-12 h duration Toxicity Tachycardia, fluid retention, lupuslike syndrome... 

Certain autoimmune syndromes can be induced by drugs. Examples include systemic lupus erythematosus following hydralazine or procainamide therapy, "lupoid hepatitis" due to cathartic sensitivity, autoimmune hemolytic anemia resulting from methyldopa administration, thrombocytopenic purpura due to quinidine, and agranulocytosis due to a variety of drugs. As indicated in other... 

There is an increase in the incidence of hydralazine-induced lupus erythematosus (LE) in the exposed population with increasing dose as can be seen in Table 7.9. However, patients who develop LE do not have a significantly different cumulative intake of hydralazine from those patients who do not develop the syndrome. This latter observation is consistent with the absence of a clear dose-response relationship in many cases of toxicity with an immunological basis. 

The LE syndrome only develops in those patients with the slow acetylator phenotype. Metabolic studies have shown that the metabolism of hydralazine involves an acetylation step (Fig. 7.82), which is influenced by the acetylator phenotype. 

Cameron HA, Ramsay LE. The lupus syndrome induced by hydralazine a common complication with low dose therapy. Brit Med J 1984 289 410-412. 

A particularly good example of a drug inducing SLE is the vasodilator hydralazine, sometimes used for the treatment of hypertension. The drug-induced lupus syndrome... 

Hydralazine has been in use since the 1950s and is usually used in combination with other drugs such as diuretics and P-blockers. In a significant number of patients, and typically after 18 months, adverse effects started to appear. These included joint and muscle pain (arthralgia and myalgia), a rash on the face and inflamed blood vessels (vasculitis). The rash on the face made afflicted patients look wolf-like, which gave rise to the name for the syndrome. Lupus erythematosus (Lupus is Latin for wolf). This disease can be caused by other drugs, such as isoniazid very occasionally and procainamide more frequently. It may also have other, unknown, causes and has some similarities with rheumatoid arthritis. 

Collagen diseases (type II) and syndromes resembling them, e.g. systemic lupus erythematosus are sometimes caused by drugs, e.g. hydralazine, procainamide, isoniazid, sulphonamides. Adrenal steroid is useful. 

Prolonged use of hydralazine at doses above 50 mg/day may cause a systemic lupus-like syndrome, more commonly in white than in black races, and in those with the slow acetylator phenotype. 

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