Hydralazine-Induced Neuropathy

Mechanism and Pathophysiology

The peripheral nervous system is affected by hydralazine, with loss of motor function, including numbness/paresthesia in extremities, loss of distal sensation, motor ataxia, weakness, and loss of deep tendon reflexes, due to axonal degeneration similar to Wallerian degeneration 1
Motor neurons feeding more distal muscles are most affected, leading to progressive denervation of muscle fibers 1
Pathological changes include swelling of axonal mitochondria, disruption of axoplasmic ground substance, and accumulation of dense bodies within neurons 1

Sensory axons are affected more than motor axons, though motor symptoms can develop 1
Morphological nerve changes may be present even before clinical signs of neuromuscular dysfunction appear, meaning subclinical neuropathy can exist 1
The risk of peripheral neuropathy increases with higher cumulative doses of hydralazine, particularly above 200 mg/day, according to the American Academy of Pediatrics and the American College of Cardiology 2, 3

Patients on long-term hydralazine therapy should be monitored for signs of peripheral neuropathy, particularly paresthesia, numbness, and tingling, and the medication should be reserved as a fourth-line or fifth-line agent for resistant hypertension to minimize adverse effects including neuropathy, as recommended by the American College of Cardiology 2, 3