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HY points followed by a quiz at the end
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Dopamine 2 (D2) receptor agonists
- Parkinson disease is caused by loss of dopamine-secreting neurons in the substantia nigra pars compacta.
- D2 agonists are usually first-line treatment.
- D2 is the main dopamine receptor in the CNS relating to motor function.
Bromocriptine
- Also used for prolactinoma. (Not mandatory that prolactinoma must be treated with bromocriptine, but I’ve seen this agent specifically as the answer on NBME exams).
Ropinirole, Pramipexole
- Also used for restless leg syndrome (have seen these as answers on NBME forms).
- Restless leg syndrome is most commonly caused by iron deficiency anemia. So check serum iron and ferritin first. If abnormal, give iron. If normal, give ropinerole or pramipexole.
Pergolide
- Another D2 agonist used for Parkinson disease. Just know its MOA.
Other Parkinson agents
Amantadine
MOA of amantadine?
- Increases presynaptic release of dopamine.
Notable side-effect of amantadine?
- Can cause livedo reticularis (a weird lacy rash on the legs).
Levodopa/carbidopa
MOA of levodopa/carbidopa?
- Levodopa (L-Dopa) is the precursor of dopamine (i.e., it’s converted to dopamine via L-Dopa decarboxylase and vitamin B6).
- L-Dopa crosses the blood-brain barrier (BBB); dopamine does not.
- If we give dopamine to a patient with Parkinson disease, not only will it not cross the BBB, but it has cardiovascular effects (which we want to avoid).
- So if we give L-Dopa, that will cross the BBB. However, it will be broken down peripherally by an enzyme called catechol-O-methyltransferase (COMT).
- Carbidopa is an analogue of L-Dopa that functions as a competitive inhibitor of COMT (i.e., COMT will act on carbidopa instead of L-Dopa), allowing L-Dopa to cross the BBB.
HY side-effect of levodopa/carbidopa for USMLE?
- Increasing the dose in some patients can cause psychosis. This is HY on the Psych shelf for 2CK. Simply reduce dose as the treatment.
- 72M + Parkinson disease on L-Dopa/carbidopa + dose was recently increased + now has auditory hallucinations; what do we do? –> answer = “decrease the dose of L-Dopa/carbidopa”; the wrong answer is “stop L-Dopa/carbidopa.”
Entacapone, Tolcapone
MOA of entacapone and tolcapone?
- Inhibit catechol-O-methyltransferase (COMT).
- Prevent breakdown of L-Dopa peripherally so that it can better cross the BBB.
Selegiline
MOA of selegiline?
- Inhibits monoamine oxidase B (MOAB).
- MOAB has ↑ effect on breaking down dopamine in the synaptic cleft.
- So selegiline prevents breakdown of dopamine in the synaptic cleft.
Benztropine, Trihexyphenidyl
MOA of benztropine and trihexyphenidyl?
- Muscarinic receptor antagonists.
- Don’t directly treat Parkinson disease as they don’t relate to dopamine.
- Purpose is to relieve symptoms caused by increased muscular rigidity (i.e., cogwheel rigidity).
- Detailed post on anti-muscarinics here.
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