Levodopa Propranolol

Kissel P, Tridon P, Andre JM. Levodopa-propranolol therapy in parkinsonian tremor. Lancet 1974 l(7854) 403-4. 

Drugs that may affect methyidopa include levodopa, nonselective beta-blockers (eg, propranolol), and ferrous sulfate or gluconate. 

It is obvious that drugs such as nifedipine and both isosorbide-5-mononitrate and isosorbide dinitrate, which have non-specific, wide absorption sites and so are well absorbed along the entire GI tract, may not be suitable candidates for GRDDS. Also, drugs that are irritant to the gastric mucosa " and those undergoing significant first-pass metabolism may have some limitations. Relevant examples of the latter type are nifedipine, propranolol, levodopa, diltiazem, metopro-lol and 5-fluorouracil. 

A 28-year-old man received interferon alfa (5 MU/day for 28 days) for chronic hepatitis B. At the end of treatment he developed a slight parkinsonian gait, and 8 days later had a fever with vomiting, insomnia, restlessness, and raised serum creatine kinase activity (4946 IU/1). He had severe akathisia with psychomotor excitement and parkinsonism. Despite treatment with clonazepam, thioridazine, propranolol, trihexyphenidyl, and bromocriptine, his condition progressively worsened. He was finally given intravenous levodopa for 8 days and recovered dramatically within the next few days. 

FIGURE 83 Therapeutic doses of levodopa produce cardiac stimulation by activating the betaj-receptor site in the heart. The cardiac stimulation is blocked by propranolol, a beta-adrenergic-receptor-blocking agent, or carbidopa, a peripheral dopa decarboxylase inhibitor. 

Most of the effects of the combined use of levodopa and beta blockers seem to be favourable, although additive hypotension can be a problem. Dopamine derived from levodopa stimulates beta-receptors in the heart, which can cause arrhythmias. These receptors are blocked by propranolol and other beta blockers. An enhancement of the effects of levodopa and a reduction in tremor has been described in 23 out of 25 patients taking propranolol, but not in 9 patients taking oxprenolol, or in another placebo-controlled study in 18 patients taking propranolol. Early evidence showed that growth hormone levels were substantially raised by propranolol or practolol [now withdrawn due to fatal reactions] in conjunction with levodopa, but no clinical relevance for this has been demonstrated. 

Camanni F, Massara F. Enhancement of levodopa-induced growth-hormone stimulation by propranolol. Lancet( 974) i, 942. 

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