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Question 21#

A 74-year-woman consults you because of tremor and difficulty completing her daily tasks on time. She has hypertension and takes hydrochlorothiazide 25 mg every morning. She does not smoke and uses alcohol infrequently. On examination, her BP is 126/84; her vital signs are otherwise unremarkable. Eye movements are normal as are her reflexes and motor strength. She moves slowly; her timed get-up-and-go test takes 24 seconds (normal 10 seconds). She has a slow resting tremor with a frequency of about 3 per second; the tremor is more prominent on the right than the left. The tremor decreases with intentional movement. Her handwriting has deteriorated and is small and crabbed.

Which therapy is most likely to improve her functional disabilities? 

a. Switching her antihypertensive to propranolol 20 mg po bid
b. Benztropine mesylate 0.5 mg po tid
c. Lorazepam 0.5 mg po tid
d. Ropinirole beginning at a dose of 0.25 mg tid
e. Carbidopa/levodopa beginning at a dose of one-half of a 25 mg/100 mg tablet tid

Correct Answer is E

Comment:

Parkinson disease (PD) is marked by depletion of dopamine-rich cells in the substantia nigra. The resulting decrease in striatal dopamine is the basis for the classic symptoms of rigidity, bradykinesia, tremor, and postural instability. Many experts consider bradykinesia to be the fundamental feature of PD. Although tremor is often the first manifestation, about 20% of patients do not have a tremor. When present, the tremor occurs at rest, is slower than most other tremors, and decreases with intentional activity (so that a watch repairman with PD is often able to function normally). The most effective treatment for PD is levodopa. Levodopa is converted to dopamine in the substantia nigra and then transported to the striatum, where it stimulates dopamine receptors. This is the basis for the drug’s clinical effect on PD. Levodopa is usually administered with carbidopa (a dopa decarboxylase inhibitor) in one pill. This prevents levodopa’s destruction in the blood and allows it to be given at a lower dose that is less likely to cause nausea and vomiting. The major problems with levodopa have been (1) limb and facial dyskinesias in most patients on chronic therapy, (2) motor fluctuations (“off-on” effects), and (3) the fact that levodopa treats PD only symptomatically and the disease process of neuronal loss in the substantia nigra continues despite drug treatment. Direct dopamine agonists (such as ropinirole or pramipexole), although less potent than dopamine itself, are often used as the first drug in younger patients. Side effects (in particular, motor fluctuations) are often less troublesome. Anti-cholinergic agents, such as benztropine mesylate, work by restoring the balance between striatal dopamine and acetylcholine; they are particularly effective in decreasing the degree of tremor. In the elderly, however, they often cause CNS side effects (especially confusion) and would not be a good choice in this elderly woman. Propranolol will help essential tremor but has no benefit in Parkinson disease. Chronic benzodiazepine use should be avoided because of the risk of habituation as well as confusion and falls in the elderly. Benzodiazepines do not improve the symptoms of PD.