Treatment of Hypertension in a Patient With Acute Intermittent Porphyria?

Bruce M. Gardner, MD


August 26, 2002


What medications are most suitable for treating hypertension in a patient with acute intermittent porphyria?

Response from Bruce M. Gardner, MD

Acute intermittent porphyria (AIP) is an inborn error of metabolism inherited via a fully identified autosomal dominant gene. The porphyrias, a group of diseases caused by various defects in the heme biosynthetic pathway, have an incidence between .05% and .1% worldwide.[1]

The clinical manifestations of AIP include paroxysms of acute abdominal pain, neurologic and psychiatric changes, and paresis. Exacerbating factors include rapid weight loss, alcohol, menstruation, and medications, especially steroid hormones. Treatment is based on infusing hematin, thereby slowing porphyrin precursor excretion, and the resultant increased levels of cytotoxic metabolites.[2] Rapid infusion of glucose also slows heme synthesis. Elevated amounts of porphobilinogen and alpha-aminolevulinic acid in urine and in plasma are confirmatory laboratory tests.

Certain medications can readily trigger attacks of AIP. Sulfonamides, barbiturates, and commonly used antiseizure medications are examples.

Hypertension is more common in "manifest" AIP patients -- those who have shown evidence of the disease -- than in individuals with latent disease or in control groups.[3] This is thought to be due to the renal vasoconstriction seen in AIP. Data from a study by Kauppinen and Mustajoki[2] showed that patients taking hydrochlorothiazide, beta-blockers, calcium-channel blockers, and nitrates remained free of AIP symptoms.

Catecholamine levels can increase up to 10-fold during an exacerbation of AIP. Consequently, beta-blockade is a very effective method of blood pressure control. Renal damage is also associated with AIP. The pathophysiologic changes seen are due to vasospastic effects, which may also underlie some of the neurologic changes seen in AIP.[4] Unfortunately, angiotensin-converting enzyme inhibitors have been associated with attacks of AIP and should not be used.

Loop diuretics are indicated in renal artery hypertension, and are safe for use in patients with AIP. Long-acting calcium-channel blockers can also be effective.

Therefore, for your patient with AIP, beta-blockers, loop diuretics, and calcium-channel blockers are safe and effective agents for the management of hypertension.