Interactions Between Levodopa and Other Drugs

Abstract

Levodopa (L-3,4 dihydroxyphenylalanine), an amino acid which is currently the most useful drug for the management of Parkinson’s disease is an excellent case in point for an important generality concerning drug treatment: Since the responses of individual patients to a specific drug may be remarkably diverse, careful individualisation of total management of the treatment is necessary in order to maximise its therapeutic effects. Relevant variables in individual response effects include the natural history of the disease under treatment, associated illnesses, drug interactions, adverse effects of other drugs, idiosyncratic reactions and diet. This article considers, many of the factors which may alter either the therapeutic efficacy or the adverse effects of levodopa in Parkinsonism or in related disorders. Levodopa absorption occurs mainly in the small intestine. The drug can be locally metabolised by decarboxylase at the gastric mucosa. High protein diet and prolonged gastric emptying time may negate the therapeutic efficacy of levodopa. Among the many inhibitors of enzyme processes important to catecholamine metabolism, only peripheral aromatic L-amino acid decarboxylase inhibitors appear to have clinical importance at present. Pyridoxine (Vitamin B6) may rapidly minimise or negate the effects of levodopa in Parkinsonism by enhancing its extracerebral metabolism. Concomitant administration of monoamine oxidase inhibitors and levodopa may cause severe hypertensive crisis. Since this phenomenon is not uniform or predictable, the effect of monoamine oxidase inhibitors in slowing degradation of cerebral dopamine cannot be utilised clinically to lower the dosage requirement of levodopa. It is well recognised that selected anticholinergic drugs have modest antiparkinsonian effects. However, in certain parkinsonian patients, these drugs will markedly delay gastric emptying and thus perhaps minimise or negate the therapeutic benefit from levodopa. Reserpine, phenothiazines, butyrophenones and tetrabenazine all may alter the function of dopaminergic pathways and hence may significantly interfere with the therapeutic efficacy of levodopa.