Mayo Clinic neurologists have discovered a drug application smart enough to alleviate orthostatic hypotension -- problems with sinking blood pressure when standing up from a sitting position -- without the unwanted effect of also causing patients' blood pressure to soar when lying down.
"This is a significant step forward for these patients," says Phillip Low, M.D., Mayo Clinic neurologist and lead study investigator. "This would be a good drug to provide the first line of treatment."
The drug, pyridostigmine, has been used for years for myasthenia gravis, a neuromuscular transmission disorder. Dr. Low hypothesized that it would also improve nerve cell transmission for orthostatic hypotension patients and trigger the reflex that controls blood pressure in all positions.
Of the 58 patients in Dr. Low's study, one-third were able to stop taking any other orthostatic hypotension medications, and others were able to lower the amount of other drugs needed. Orthostatic hypotension is especially common in those over age 70. In general, blood pressure control lessens as one ages, according to Dr. Low. Common causes of orthostatic hypotension include diabetes, autonomic neuropathy, multiple system atrophy, pure autonomic failure and Parkinson's disease. Certain drugs, such as diuretics and medication used to control blood pressure, are also common catalysts for the condition. Studies conducted at Mayo Clinic by Peter Dyck, M.D., neurologist, indicate 10 percent of diabetics have orthostatic hypotension.
The challenge with trying to fix this condition, according to Dr. Low, is that most medications that increase blood pressure raise blood pressure in all positions. Thus, the drugs would work for patients with orthostatic hypotension when they stood up, but their blood pressure would be too high when lying down, increasing their risk of stroke. Dr. Low felt that this price was too high, and that treating with medications that raised blood pressure while standing but raised blood pressure while lying down amounted to trading one problem for another.
"We wanted a 'smart drug' that would only increase blood pressure when standing up, and not when lying down," says Dr. Low. Pyridostigmine works at the level of the autonomic ganglion, which has minimal nerve signaling traffic when lying down. When standing up, however, nerve signaling traffic in the autonomic ganglion increases, so the researchers theorized that a drug that affected the autonomic ganglion would improve orthostatic hypotension patients' standing blood pressure but not increase the blood pressure while lying down.
After a small, open trial of 15 subjects in which the pyridostigmine performed effectively as hoped, the investigators proceeded to the current double-blinded study of 58 patients. The patients either received placebo, pyridostigmine alone or pyridostigmine in combination with one of two low dosages of midodrine, a drug previously proven to improve orthostatic hypotension.