HY USMLEQ#11 Neurology/Pharmacology Step 1/3
Level = Step 2CK/3 (inspired from Uworld Step 3 Qbank )
A 64-year-old man diagnosed with Parkinson's disease is prescribed oral carbidopa/levodopa. The patient then sees improvement of the freezing motor symptoms within 2 weeks. But the problem is that he frequently experiences nausea and lightheadedness within 15 minutes of taking the medication. When the dosage of the carbidopa is increased, the adverse effects are reduced.
What do the following options state about the mechanism of action of carbidopa?
A. Activates dopamine receptors in the central nervous system
B. Blocks dopamine receptor in the gut and systemic vasculature
C. Increase conversion of levodopa to dopamine in the brain
D. Decreases the conversion of levodopa to dopamine in the liver and the peripheral blood
E. Decreases the breakdown of dopamine in the CNS
✅ Correct Answer: D. Decreases the conversion of levodopa to dopamine in the liver and the peripheral blood
Education Objective: Parkinson's disease is an essential disease that involves the degeneration of the dopaminergic neurons. Hence, we give levodopa, which is a precursor to dopamine.
In the peripheral tissues, there is an enzyme known as DOPA decarboxylase, which rapidly converts L-DOPA into dopamine.
Also, increasing the amount of dopamine in the brain leads to a decrease in the unpleasant adverse effects. Low doses of carbidopa may not be sufficient to prevent the adverse effects of Carbidopa, such as nausea and vomiting.
❌ A. Dopamine agonists, for example, pramipexole and bromocriptine, directly activate the dopamine receptors.
❌ B. Enteric dopamine antagonist (for example, metoclopramide) blocks dopamine receptors in the gut and the systemic vasculature and acts as a prokinetic agent in patients with gastrointestinal hypomotility. In patients with/ low doses of carbidopa, hence more dopamine excess will lead to more stimulation of the enteric center in the brain stem ( which is outside of the BBB) rather than gastrointestinal hypomotility.
❌ C.Carbidoa doesn't cross the BBB, hence it will not have any effect on the conversion of L-DOPA into dopamine in the brain.
❌ E. This refers to the drug selegiline, which is used to delay the clinical progression of Parkinson's disease by inhibiting monoamine oxidase B in the brain.