SOURCE: Mental Health Business Week via IncRx.com via NewsRx.com and
NewsRx.net
October 30, 2004
Pg. 48
HEADLINE: MAYO CLINIC;
Mayo Clinic finds effective remedy for blood pressure drop when standing
up
BODY:
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," said Phillip
Low,
MD, 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. 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 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
Low.
Common causes of orthostatic hypotension include diabetes, autonomic
neuropathy,
multiple system atrophy, pure autonomic failure and Parkinson 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, MD, neurologist, indicate 10% of diabetics have orthostatic
hypotension.
The challenge with trying to fix this condition, according to 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. Low felt that this price was too high.
"We wanted a 'smart drug' that would only increase blood pressure
when
standing up, and not when lying down," said 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.
The effects of the drugs were measured 1 hour post-treatment.
Pyridostigmine
significantly improved the patients' standing blood pressure without
elevating
blood pressure while lying down. The positive effects of the drug were
even
further improved when combined with low-dose midodrine. Improvement of
blood
pressure was associated with improvement of symptoms while standing.
Side effects from pyridostigmine were minor and transient, including
some
abdominal cramping or need to go to the bathroom more often than usual.
Paola Sandroni, MD, another Mayo Clinic neurologist, conducted a
follow-up
study of the first 45 patients in the study led by Low; the follow-up
study
occurred an average of 19.5 months after the first trial. Detailed
information
was available on 32 patients, and 75% reported either good or excellent
results
from the pyridostigmine treatment. Approximately one in four were able to
manage
on pyridostigmine alone, and one in three needed other medications, yet
were
able to reduce the dose of the other medication (e.g., midodrine or
fludrocortisone).
"By the time they come to see us at Mayo Clinic, the majority of our
orthostatic hypotension patients have had multiple treatments and have
not done
very well," said Low. "They are very grateful to have found this drug
[pryridostigmine]."
The next step in the orthostatic hypotension research will involve
seeking
out an even smarter drug combination involving pyridostigmine that might
work on
multiple levels.
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