A drug traditionally used to treat myasthenia gravis shows potential benefit for reducing symptoms of orthostatic hypotension without raising blood pressure when people lie down, according to results of a double-blind, controlled clinical trial.
A drug traditionally used to treat myasthenia gravis shows potential benefit for reducing symptoms of orthostatic hypotension without raising blood pressure when people lie down, according to results of a double-blind, controlled clinical trial.
Orthostatic hypotension (OH) - a sudden fall in blood pressure when a person stands up - is a common problem in elderly adults as well as in people with Parkinson's disease, multiple system atrophy, diabetes, and a variety of other disorders. OH is caused by a loss of normal function in the autonomic nervous system, which controls the tightening and relaxing of blood vessels necessary to maintain normal blood pressure. People with OH may experience dizziness, lightheadedness, blurred vision, or fainting when they stand.
The standard treatment for OH is a drug called midodrine, which helps to alleviate symptoms. However, standard doses of midodrine also raise blood pressure when people lie down. Now, researchers led by Phillip Low, M.D., of the Mayo Clinic in Rochester, Minnesota, have shown that another drug called pyridostigmine can alleviate many of the symptoms of OH, either alone or in combination with a low dose of midodrine. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) and is published in the April 2006 issue of the Archives of Neurology.*
Midodrine and pyridostigmine both work by causing blood vessels to constrict. Midodrine causes this constriction continuously while it is in the bloodstream. On the other hand, pyridostigmine is thought to work by slowing breakdown of the nerve-signaling chemical acetylcholine, which is used by a cluster of nerve cells called the autonomic ganglion. The autonomic ganglion transmits signals from the central nervous system to the peripheral nervous system. Signals from the autonomic ganglion are minimal when people are lying down, but increase dramatically whenever they stand up or undergo other "orthostatic stress" that causes the body to adjust to maintain normal blood pressure. Therefore Dr. Low and his colleagues theorized that pyridostigmine would increase blood pressure only when people stand up, and that it would work in proportion to the amount of orthostatic stress they experience with different activities.
The study compared the use of pyridostigmine, with or without low-dose midodrine, to a placebo in 58 patients with OH due to severe autonomic nervous system failure. The patients received four different treatments in random order on successive days: 60 mg of pyridostigmine alone, pyridostigmine plus 2.5 mg of midodrine, pyridostigmine plus 5 mg midodrine, and placebo. The researchers measured blood pressure and heart rate when the patients laid down and while they were standing, once every hour for 6 hours after the treatment was given. They also rated the patients' symptoms on a scale of 1 to 5, with 5 indicating excellent improvement, and they took blood samples at the start of treatment and 1 hour later in order to see how the treatment affected blood levels of the nerve-signaling chemicals norepinephrine, epinephrine, and dopamine.
The results showed that at 1 hour after a single administration of the study medication, both pyridostigmine alone and pyridostigmine plus 5 mg of midodrine significantly improved blood pressure when the patients stood up, compared with the placebo. None of the treatments caused increased blood pressure when patients were lying down.
"Pyridostigmine is a 'smart drug,'"says Dr. Low. "It only works when you need it."