Mydriasis may occur and may precipitate an attack of acute glaucoma in some patients. Other reported but rare adverse effects include various blood dyscrasias; a positive Coombs’ test with evidence of hemolysis; hot flushes; aggravation or precipitation of gout; abnormalities of smell or taste; brownish discoloration of saliva, urine, or vaginal secretions; priapism; and mild—usually transient—elevations of blood urea nitrogen and of serum transaminases, alkaline phosphatase, and bilirubin.
A drug holiday (discontinuance of the drug for 3–21 days) may temporarily improve responsiveness to levodopa and alleviate some of its adverse effects but is usually of little help in the management of the on-off phenomenon. Furthermore, a drug holiday carries the risks of aspiration pneumonia, venous thrombosis, pulmonary embolism, and depression resulting from the immobility accompanying severe parkinsonism. For these reasons and because of the temporary nature of any benefit, drug holidays are not recommended.
Pharmacologic doses of pyridoxine (vitamin B6) enhance the extracerebral metabolism of levodopa and may therefore prevent its therapeutic effect unless a peripheral decarboxylase inhibitor is also taken. Levodopa should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their discontinuance because such a combination can lead to hypertensive crises.
Levodopa should not be given to psychotic patients because it may exacerbate the mental disturbance. It is also contraindicated in patients with angle-closure glaucoma, but those with chronic open-angle glaucoma may be given levodopa if intraocular pressure is well controlled and can be monitored. When combined with carbidopa, the risk of cardiac dysrhythmia is slight, even in patients with cardiac disease. Patients with active peptic ulcer must be managed carefully, since gastrointestinal bleeding has occasionally occurred with levodopa. Because levodopa is a precursor of skin melanin and conceivably may activate malignant melanoma, it should be used with particular care in patients with a history of melanoma or with suspicious undiagnosed skin lesions; such patients should be monitored regularly by a dermatologist.
Drugs acting directly on postsynaptic dopamine receptors may have a beneficial effect in addition to that of levodopa (Figure 28–5). Unlike levodopa, they do not require enzymatic conversion to an active metabolite, act directly on the postsynaptic dopamine receptors, have no potentially toxic metabolites, and do not compete with other substances for active transport into the blood and across the blood-brain barrier. Moreover, drugs selectively affecting certain (but not all) dopamine receptors may have more limited adverse effects than levodopa. A number of dopamine agonists have antiparkinsonism activity. The older dopamine agonists (bromocriptine and pergolide) are ergot (ergoline) derivatives (see Chapter 16) and are rarely—if ever—used to treat parkinsonism. Their side effects are of more concern than those of the newer agents (pramipexole and ropinirole).