Magazine article Drug Topics

Keeping the Pressure Up

Magazine article Drug Topics

Keeping the Pressure Up

Article excerpt

For the first time, the Food & Drug Administration has approved a medication, ProAmatine (midodrine, Roberts Pharmaceutical Corp.), for the treatment of orthostatic hypotension, a condition in which blood pressure drops as a person stands up. Common symptoms of orthostatic hypotension include lightheadedness, dizziness, fatigue, and fainting. The condition is defined by a drop in systolic blood pressure of at least 20 mmHg or a drop in diastolic blood pressure of at least 10 mmHg within three minutes of standing.

While it is normal for blood pressure to drop when a person stands up, Phillip Low, M.D., director of the Autonomic Disorders Research Center and professor of neurology at the Mayo Clinic, Rochester, Minn., explained that in most people, the transient lightheadedness quickly goes away as the autonomic nerves in the blood vessels and heart redistribute blood and regulate blood pressure. In patients with orthostatic hypotension, nerve or brain damage causes the compensatory mechanism to malfunction. Orthostatic hypotension is a common sequela of neuropathies caused by diabetes, viral infections, Parkinson's disease, or some medications.

Low explained that patients who suffer from orthostatic hypotension are often unable to think clearly. "Every time the patient stands up, there is not enough blood returning to the brain, so the lack of oxygen in the brain causes dizziness, inability to think clearly, and weakness due to the brain's being starved of oxygen." According to Low, patients who are successfully treated for orthostatic hypotension, especially the elderly, often feel "like a cloud has been lifted."

Midodrine, a prodrug that is converted to desglymidodrine, is an alpha-1 agonist. To explain how midodrine works, Low first reviewed some basic physiology. "Nerves usually send a neurotransmitter [norepinephrine] that binds to receptors on blood vessels," he said. "When nerves are damaged, they can no longer deliver neurotransmitters, but receptors on the blood vessels remain there and may increase in number. [Midodrine] binds to receptors and activates blood vessels."

Clinical trials have shown that midodrine increases one-minute standing blood pressure in patients, but data are not yet available on the clinical ramifications of the drug, such as its effect on a patient's ability to perform activities of daily living. Eatontown, N.J.-based Roberts Pharmaceutical will conduct phase IV studies to confirm the drug's clinical benefit.

In the clinical trials, the most common adverse event was elevated supine blood pressure. …

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