Page 510 - Basic _ Clinical Pharmacology ( PDFDrive )

496 SECTION V Drugs That Act in the Central Nervous System

Levodopa alone
100% 30% 1–3%
Brain
Blood

Levodopa
dose Gut

70% 27–29%

Metabolism Peripheral
in the tissues
GI tract (toxicity)

Levodopa with carbidopa
100% 60% 10%
Levodopa Blood Brain
dose Gut

40% 50%

Metabolism Peripheral
in the tissues
GI tract (toxicity)

FIGURE 28–4 Fate of orally administered levodopa and the effect of carbidopa, estimated from animal data. The width of each pathway
indicates the absolute amount of the drug at each site, whereas the percentages shown denote the relative proportion of the administered
dose. The benefits of co-administration of carbidopa include reduction of the amount of levodopa required for benefit and of the absolute
amount diverted to peripheral tissues and an increase in the fraction of the dose that reaches the brain. GI, gastrointestinal. (Data from Nutt JG,
Fellman JH: Pharmacokinetics of levodopa. Clin Neuropharmacol 1984;7:35.)

B. Cardiovascular Effects C. Behavioral Effects
A variety of cardiac arrhythmias have been described in patients A wide variety of adverse mental effects have been reported,
receiving levodopa, including tachycardia, ventricular extrasysto- including depression, anxiety, agitation, insomnia, somnolence,
les, and rarely, atrial fibrillation. This effect has been attributed to sleep attacks, confusion, delusions, hallucinations, nightmares,
increased catecholamine formation peripherally. The incidence of euphoria, and other changes in mood or personality. Such adverse
such arrhythmias is low, even in the presence of established cardiac effects are more common in patients taking levodopa in combina-
disease, and may be reduced still further if the levodopa is taken in tion with a decarboxylase inhibitor rather than levodopa alone,
combination with a peripheral decarboxylase inhibitor. presumably because higher levels are reached in the brain. They
Postural hypotension is common, but often asymptomatic, and may be precipitated by intercurrent illness or surgery. It may be
tends to diminish with continuing treatment. Hypertension may necessary to reduce or withdraw the medication. Several atypi-
also occur, especially in the presence of nonselective monoamine cal antipsychotic agents that have low affinity for dopamine D
2
oxidase inhibitors or sympathomimetics or when massive doses of receptors (clozapine, olanzapine, quetiapine, and risperidone; see
levodopa are being taken. Chapter 29) are now available and may be particularly helpful in