Lupus-like syndrome, hydralazine

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) ... 

One side effect unique to hydralazine is a dose-dependent drug-induced lupus-like syndrome. Hydralazine is eliminated by hepatic A-acetyltransferase. This enzyme displays genetic polymorphism, and slow acetylators are especially prone to develop drug-induced lupus with hydralazine. This syndrome is more common in women and is reversible on discontinuation. Drug-induced lupus may be avoided by using less than 200 mg hydralazine daily. Other side effects of hydralazine include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it is still used with isosorbide dinitrate in patients with heart failure (especially African-Americans) and is useful in patients with severe chronic kidney disease and kidney failure. 

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... 

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... 

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. 

The lupus-like syndrome (SED-9, 318) with hydralazine occurs particularly in slow acetylators (and only rarely in fast acetylators) and in patients with the HLA-DR4 antigen. Blood dyscrasias and necrotizing vasculitis are additional features. 

Thrombocytopenia has been reported in infants whose mothers were taking hydralazine with no evidence of the lupus-like syndrome (11). 

Although hydralazine was implicated as the cause of a maternal and neonatal lupus-like syndrome, the toxemia and low birth weight of the child make interpretation of the case difficult. 

Vasodilators Hydralazine Salt and water retention, marked tachycardia Lupus-like syndrome (but lacking renal effects)... 

Methyldopa is the only antihypertensive drug associated with hemolytic anemia (usually preceded by a positive Coombs test). Hydralazine is also associated with autoimmune toxicity, but this takes the form of a lupus-like syndrome with butterfly facial rash, fever, joint and muscle pains, and antinuclear antibodies. The answer is (D). 

A/-Acetyltransferase Hydralazine, procainamide Increased risk of lupus-like syndrome in slow acetylators possible increas cardiotoxicity with procainamide in fast acetylators... 

The mechanisms by which antinuclear antibodies are produced are not completely elucidated. It seems that the responsible drugs produce a lupus-like syndrome de novo rather than activating latent SLE. Hydralazine and procainamide... 

Since the original reports by Perry and Schroder (1954) and Dunstan et al. (1954) describing a lupus-like syndrome inducible with hydralazine, and by Ladd (1962) with procainamide, much attention has been paid to the relationship of drug-induced lupus with the established clinical entity - systemic lupus erythematosus. 

A Cochrane review failed to find any randomized placebo-controlled studies of hydralazine [103 ]. The reviewers noted that reported adverse reactions include reflex tachycardia, hemolytic anemia, vasculitis, glomerulonephritis, and lupus-like syndrome. Given the availability of antihypertensive... 

Urinary tract Hydralazine has been associated with ANCA positive pauci-immune glomerulonephritis and pulmonary alveolar hemorrhage [105 ]. In this case anti-double-stranded DNA and antihistone antibodies were present in the absence of full classification criteria for drug-induced lupus-like syndrome. The symptoms and renal function improved after withdrawal of hydralazine and a short course of cyclophosphamide and prednisone. 

Immunologic The incidence of lupus-like syndrome associated with hydralazine is 5-8% per year [106 ]. The proposed mechanisms are related to drug metabolites acting as haptens for T cell responses. 

In a matched case-control study using UK general practice electronic records exposure to hydralazine was associated with a substantially increased risk of lupus-like syndrome compared with deliberately selected comparator drugs [108. However, drugs did not seem to be a major cause of lupus-like syndrome, accounting for only 12% of incident cases. 

In a matched nested case-control study using data from the UK General Practice Research Database (GPRD) there were 875 cases of a lupus-like syndrome, of which 12% ( = 107) had evidence of a prescription for one or more of the suspected drugs, and they were compared with 3632 matched controls [68 ]. There was an increased risk of lupus-like syndrome with hydralazine (OR = 6.6, 95% CI = 1.03, 43), minocycline (OR = 4.2, 95% Cl = 2.7, 6.8) and carbamazepine (OR = 1.9, 95%... 

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

Certain drugs, such as hydralazine, procainamide, isoniazid, chlorpromazine, and minocycline, can provoke lupus-like manifestations (D Cruz, 2000). Clear differences between systemic lupus erythematosus and lupus syndrome can be identified — hence the recommended different terminology. Typical clinical features of the drug-induced lupus syndrome include arthralgias, arthritis, rash, and... 

Hydralazine (Apresoline) Directly relaxes arterioles (not veins) independent of sympathetic interactions. Causes decrease in blood pressure leading to reflex tachycardia and increased cardiac output. Directly increases renal blood flow. Moderate hypertension. May be used in pregnant women who are hypertensive. Reflex tachycardia, palpitations, fluid retention, systemic lupus erythematosis-liKe syndrome. Chronic therapy may lead to peripheral neuritis (due to interference with vitamin B6 metabolism in neural tissue). 

Reeves PR, Case DE, Jepson HT et al. (1978) Practolol metabolism in metabolism in human subjects. J Pharmacol Exp Ther 205(2) 489-498 Reinhardt DJ, Waldron JM (1954) Lupus erythematosus-like syndrome complicating hydralazine (Apresoline) therapy. JAMA 155 1491-1492 Riddiough MA (1977) Preventing, detecting and managing adverse reactions of antihypertensive agents in the ambulant patient with essential hypertension. Am J Hosp Pharm 45(5) 465-477... 

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. 

Peripheral Vasodilators and Other AntihypertensIves - L-6150 (XXXl), which has hydralazine-like activity with less toxicity, shows no lupus erythema-tosus-llke syndrome in Collie dog studiesA group of 3-amlno-4-halosydnone imines related to PR-G-138 (XXXII) show comparable oral activity to the parent compound in hypertensive rats (ca. 10 mg/kg). - Diazoxide analogs with the benzene ring replaced by thiophene, e.g. 

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