Hydralazine adverse effects

The drug hydralazine is a vasodilator used for the treatment of hypertension. In a significant proportion of individuals, it causes a serious adverse effect, drug-induced systemic lupus erythematosus (SLE). This is a systemic kind of toxic effect, as there is no particular target organ or tissue. It is an example of immune-media ted toxicity that involves autoimmunity and shows a number of interesting features. 

What are the predisposing factors identified in human patients that are important in the immune-media ted adverse effect lupus erythematosus caused by the drug hydralazine ... 

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. 

The calcium channel blockers have had very limited use in pregnancy. The absence of reports of fetal deaths, malformations, or other maternal or neonatal adverse effects cannot therefore be construed as indicating safety. However, a comparison of nifedipine and hydralazine in 54 patients with severe pre-eclampsia showed that nifedipine is more effective, allowing delivery of more mature infants (134). 

Compared with placebo, the combination of hydralazine and isosorbide dinitrate (ISDN) reduced mortality in patients receiving diuretics and digoxin (but not ACE inhibitors or /3-blockers). However, another trial comparing the combination with an ACE inhibitor found that mortality was lower in the ACE inhibitor group. Adverse effects (primarily headache and gastrointestinal complaints) with combined hydralazine-ISDN were common, limiting their use in many patients. Patient compliance also was an important issue because hydralazine-ISDN therapy was given four times daily in these trials. Whether less frequent administration provides equivalent benefit is unknown. 

Current guidelines recommend that hydralazine-ISDN should not be used instead of ACE inhibitors as standard therapy in heart failure or substituted for ACE inhibitors in patients who are tolerating an ACE inhibitor. The combined use of hydralazine-ISDN may be considered a therapeutic option in patients unable to take an ACE inhibitor or an ARB because of renal insufficiency, hyperkalemia, or possibly hypotension. However, it should be anticipated that compliance with this regimen will be poor and the risk of adverse effects high. Therefore, given the proven benefits and low risk of adverse effects, many clinicians now prefer ARBs in patients who cannot tolerate an ACE inhibitor. There are no controlled trials evaluating the benefits of adding hydralazine-ISDN therapy to patients who remain symptomatic despite ACE inhibitor and/or /S-blocker treatment. 

Hydralazine is the first systemic vasodilator drug advocated for initial treatment in patients with primary pulmonary hypertension. Rubin and Peter (1980) reported that short-term and long-term administration of hydralazine (200-300 mg/day) improved hemodynamics during rest and exercise in patients with primary pulmonary hypertension. The use of hydralazine, however, is not without hazard. In one study with 13 patients (Danahy et al., 1979), hydralazine produced only modest decreases in pulmonary arteriolar resistance and serious adverse effects that included hypotension (resulting in one death), renal insufficiency, and systemic arterial hypoxemia. 

Two types of adverse effects occur after the use of hydralazine. The first, which are extensions of the pharmacological effects of the drug, include headache, nausea, flushing. 

In the treatment of hypertension, a major use of beta-blockers is in combination with hydralazine. The direct vasodilators bring about reflex cardiac stimulation, and beta-blockers prevent these adverse effects (see also Figure 67). Beta-blockers also reduce blood pressure by exerting a central effect or a peripheral action, or both, which decreases renin activity. Metoprolol and atenolol are beta selective, and they are safer agents in patients with asthma, diabetes mellitus, or low-renin hypertension. Some beta-blocking agents such as pindolol have intrinsic sympathomimetic activity and may be used in the treatment of pronounced bradycardia (sick sinus syndrome). Unlike propranolol, metoprolol is not a very lipid-soluble... 

Other adverse effects are caused by immunological reactions, of which the drug-induced lupus syndrome is the most common. Hydralazine also can result in an illness that resembles serum sickness, hemolytic anemia, vasculitis, and rapidly progressive glomerulonephritis the mechanism of these autoimmune reactions is unknown. The drug-induced lupus syndrome usually occurs after at least 6 months of continuous treatment with hydralazine, and its incidence is related to dose, sex,... 

Drug-induced lupus is a major adverse effect of procainamide and hydralazine.Iso-lated case reports have incriminated other compounds such as reserpine, methyl-... 

The pattern of adverse vasodilator effects with minoxidil is similar to, but more severe than, that of hydralazine and fluid retention can be troublesome. 

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