Review Question - QID 216608

This patient presents with a “pill-rolling” tremor, bradykinesia, and cogwheel rigidity, indicative of Parkinson disease. She is started on a 2-drug combination containing a catecholamine precursor, which refers to carbidopa-levodopa, of which carbidopa serves to increase central nervous system (CNS) availability of levodopa.

Carbidopa inhibits 1-aromatic amino acid decarboxylase by irreversibly binding to pyridoxal 5’-phosphate, a cofactor used by the enzyme. Normally, this enzyme metabolizes levodopa to dopamine, which cannot cross the blood-brain barrier. Excessive levodopa metabolism in the periphery reduces the quantity of levodopa that can enter the central nervous system to be converted to dopamine. Since carbidopa cannot cross the blood-brain barrier, it selectively inhibits the peripheral conversion of levodopa to dopamine, thereby allowing more levodopa (which can cross the blood-brain barrier) to enter the central nervous system and exert its therapeutic effects. Once in the CNS, levodopa can be converted to dopamine and mitigate the effects of Parkinson disease.

Leyden and Tadi review the pharmacology of carbidopa. They outline its mechanism as well as several side effects, including dyskinesias. They recommend close monitoring and titration of drug doses in patients.

Incorrect Answers:
Answer 1: Conversion into dopamine in the brain describes levodopa, the catecholamine precursor component of the 2-drug combination. Carbidopa cannot cross the blood-brain barrier and stays in the periphery. Levodopa is the active agent that allows for increased dopamine production in the brain.

Answer 2: Increasing the binding of a catecholamine precursor in peripheral tissues is incorrect because carbidopa inhibits levodopa (catecholamine precursor) conversion to dopamine in the periphery. Its purpose is not to affect binding. Levodopa must first be converted into dopamine before binding dopamine receptors in peripheral tissues.

Answer 4: Increasing the permeability of the blood-brain barrier to a catecholamine precursor is incorrect because carbidopa does not actually increase the permeability of the blood-brain barrier. Carbidopa merely inhibits peripheral decarboxylation of levodopa (catecholamine precursor) so that it can enter the brain.

Answer 5: Preventing degradation of dopamine describes the action of monoamine oxidase inhibitors such as selegiline or rasagiline. These can be used in Parkinson disease but are not directly combined with levodopa. In contrast, carbidopa prevents the degradation/metabolism of levodopa, not dopamine, in the periphery.

Bullet Summary:
Carbidopa is given in combination with levodopa for the treatment of Parkinson disease to prevent the peripheral conversion of levodopa to dopamine, thus increasing levodopa availability to the central nervous system.