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[Medical Sciences Bulletin]
 
Medical Sciences Bulletin Contents
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Parkinson's Disease: Treating Foot Cramps
 
Reprinted from Medical Sciences Bulletin published by Pharmaceutical
Information Associates, Ltd.
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Drugs mentioned:
 
     levodopa/carbidopa (Sinemet/DuPont Pharmaceuticals)
     selegiline (Eldepryl/Somerset)
     pergolide (Permax/Lilly)
     bromocriptine (Parlodel/Sandoz)
     trihexyphenidyl (Artane/Lederle)
     cyclobenzaprine (Flexeril/Merck)
     baclofen (Lioresal/Geigy)
     clonazepam (Klonopin/Roche)
     botulinum toxin (Botox/Allergan).
 
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Aching and cramping of the feet are common complaints, often occurring
after injury (strains and sprains) or excessive exercise, or in association
with arthritis or poor circulation in the legs. In Parkinson's disease
(PD), cramping of the feet is also very common, but the cause is central
rather than peripheral. Foot cramping is just one of several focal
dystonias -- abnormal, sustained tightening of muscles -- that appear to be
due to neurochemical abnormalities in the basal ganglia, that part of the
brain involved in PD. Patients show a particular type of cramping
characterized by downward clenching of the toes or inward turning of the
foot. Cramping can occur throughout the day or night, and can be especially
annoying when it interferes with sleep. Foot cramping is more common among
those individuals whose PD affects just one side of the body.
 
Dystonias are often mistaken for other causes of cramping or painful
muscles. Some individuals with orthopedic foot problems, such as "hammer
toes," are actually suffering from Parkinsonian dystonia. Patients with
dystonias may be entirely unaware of any Parkinsonism; indeed, muscle
cramping can precede the onset of Parkinsonian symptoms by years. There are
no laboratory tests that distinguish dystonia from other causes of
cramping, although a thorough neurologic examination and specialized tests
should pinpoint the cause. Some dystonic features -- such as blepharospasm
(involuntary closing of the eyelids) or torticollis (involuntary turning of
the neck) -- are common in the general population.
 
In the PD patient receiving levodopa/carbidopa (Sinemet/DuPont
Pharmaceuticals), focal dystonias may be caused by either too much of the
drug or too little. Patients may experience dystonia when peak drug levels
are attained 1 to 2 hours after administration, or hours later when drug
effects wear off. Changing the dose or dosage schedule of Sinemet, or using
the sustained-release product (Sinemet CR) may help. The monoamine-oxidase
B inhibitor selegiline (Eldepryl/Somerset) may also help. A bedtime dose of
Sinemet CR, pergolide (Permax/Lilly), or bromocriptine (Parlodel/Sandoz)
may prevent foot dystonia during early- morning hours. Some patients
respond to anticholinergics such as trihexyphenidyl (Artane/Lederle),
muscle relaxants such as cyclobenzaprine (Flexeril/Merck) and baclofen
(Lioresal/Geigy), and the anticonvulsant clonazepam (Klonopin/Roche).
Another treatment giving excellent relief is botulinum toxin
(Botox/Allergan). Injected into the dystonic or cramping muscle, botulinum
toxin reduces the intensity of the spasms; the effects may last months
after injec-tion. The toxin is also used for Parkinsonian tremors, benign
essential tremor, and a number of dystonias not always associated with PD.
These include blepharospasm, torticollis, dysphonia (cramping of the vocal
cords), strabismus (wandering eye), stuttering, and large-muscle spasms
associated with conditions such as stroke, head trauma, and multiple
sclerosis.
 
A careful evaluation of the temporal relationship between foot cramping and
the levodopa dosage schedule should help the physician decide how best to
treat this uncomfortable manifestation of PD. Modifying the levodopa
regimen or adding other anti-PD agents can alter signals from the brain
that trigger the contractions, or the muscle itself can be "paralyzed" with
botulinum toxin. (LeWitt PA. UPF Newsl. 1993; #3: 3-4).
 
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[Medical Sciences Bulletin]
 
Medical Sciences Bulletin Contents
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Psychotropics and the Risk of MI in Women
 
Reprinted from Medical Sciences Bulletin , published by Pharmaceutical
Information Associates, Ltd.
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During their analysis of data from a case-control study of fatal myocardial
infarction (MI) in women aged 16-39, Thorogood et al. found that the risk
of fatal MI was increased in current users of oral contraceptives (relative
risk 1.9) and in current cigarette smokers (relative risk 19.3.), which is
about what they expected. But they also found that current use of
psychotropic drugs was associated with an increased risk of MI (relative
risk 16.9), which was entirely unexpected. In addition, they found a
three-fold increase in the risk of subarachnoid hemorrhage and a similar
but smaller increase in the risk of venous thromboembolism.
 
Fifty-seven women (about 35% of the total cases of fatal MI) had used
psychotropic drugs, and 22 of these were "current users" (defined as "use
within one month of death"). By contrast only 17.8% of controls (who died
of causes other than MI) had ever used psychotropic drugs, and only 1.6%
were current users at the time of death. The most commonly used
psychotropics were benzodiazepines and tricyclic antidepressants, with
diazepam and dothiepin heading the list. Drug toxicity is probably not
responsible for the association between psychotropics and MI. While
tricyclics may increase the risk of arrhythmias, benzodiazepines are free
of adverse cardiac effects. "There are several possible explanations for
the observed association," wrote Thorogood et al in a recent issue of The
Lancet. "Cardiovascular morbidity may be increased in patients with
psychiatric disorders or there may be differential survival of women with a
history of psychiatric illness." Several prior studies found an increased
incidence of heart disease in patients with panic disorder, phobic anxiety,
psychosis, and major depression. Moreover, depression was found to be a
significant predictor of mortality within the first year after infarction.
 
An alternate explanation is that nonspecific symptoms of heart disease may
have prompted these women to seek medical advice, but rather than (or
possibly in addition to) being evaluated for heart disease, they received a
prescription for psychotropic drugs. After all, chest pain in young women
is more commonly associated with anxiety and depression than it is with
obstructive coronary disease. Another explanation for the observation has
to do with the association between psychiatric conditions and the
mechanisms of myocardial ischemia. According to an editorialist writing in
the same issue of The Lancet, "Stated briefly, coronary artery spasm can
cause chest pain, ventricular arrhythmias, and myocardial infarction;
hyperventilation is a cardinal feature of what is now termed panic
disorder; and panic disorder is very common, affecting 2-5% of the general
population and 10-14% of patients in cardiology practice. About 80% of
those affected are women." (Ed. Lancet 1992; 340: 1069-1070.)
 
In studies of risk factors for certain diseases, care is needed in
interpreting incidental findings, said Thorogood et al., "but sometimes
such an association is so strong that it warrants reporting." Exactly why
psychotropic drug usage is associated with a 17-fold increase in the risk
of fatal MI in young women is not known, nor is it known whether this
observation holds for older women or for men. "Nevertheless psychotropic
drugs are in widespread use and cardiovascular disease is a major cause of
premature mortality, in women as well as in men, and the association
reported here requires further investigation." (Thorogood M et al. Lancet
1992; 340: 1067-1068.)
 
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[Medical Sciences Bulletin]
 
Medical Sciences Bulletin Contents
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Nefazodone for Depression
 
Reprinted from Medical Sciences Bulletin , published by Pharmaceutical
Information Associates, Ltd.
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[-] Indication: Depression
 
     [-] Drug Tradename: Serzone
     [-]Manufacturer: Bristol-Myers Squibb
 
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Nefazodone (Serzone/Bristol-Myers Squibb) is a serotonin reuptake inhibitor
structurally related to trazodone. The drug also appears to block
postsynaptic serotonin receptors. In comparative studies of patients with
major depression, nefazodone proved more effective than placebo and better
tolerated than imipramine. It has little effect on hemodynamics and is less
sedating than other antidepressants.
 
Nefazodone has some interesting effects: it raises oral temperature, causes
a dose-related increase in prolactin levels, increases REM sleep, and has
shown analgesic activity (it may be a useful adjunct in pain management).
 
Although nefazodone is nonsedating and does not appear to potentiate the
depressant effects of alcohol, the drug interacts with certain
benzo-diazepines (e.g., triazolam, Halcion/Upjohn). (Frewer LJ, Lader M.
Int Clin Psychopharmacol. 1993; 8: 13-20. Walsh AE et al. Biol Psychiatr.
1993; 33: 115-119.)
 
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