Parkinson's Drugs Flashcards
What is the difference between Parkinson’s disease and Parkinson syndrome?
Parkinson’s disease is idiopathic or primary while Parkinson syndrome is induced or secondary.
Which neuronal activity is decreased in Parkinson?
Degeneration of dopaminergic neurons in the substantia nigra plus reduced striatal dopamine
Why does MPTP causes Parkinsonism?
MPTP is metabolized by MAOB and forms the metabolite MPP+ which causes dopaminergic neurons to die.
Which drugs can reduce MPTP toxicity?
MOA B inhibitors Selegiline and Rasagiline
How is levodopa metabolized?
This is a prodrug converted to dopamine by aromatic amino acid decarboxylase (AAAD), also called dopa decarboxylase.
Which transporter does levodopa use to enter CNS?
Levodopa enters brain by L-amino acid transporter (but dopamine does not).
Why carbidopa always combine with levodopa?
Levodopa when given alone is mostly metabolized in the periphery leading to adverse effects and lack of efficacy due to too little drug entering the brain. Levodopa when combined with carbidopa prevents this peripheral conversion.
What is the MOA of carbidopa?
peripheral dopa decarboxylase inhibitor (aka aromatic amino acid decarboxylase/AAAD inhibitor)
What are the ADRs of levodopa?
Arrhythmias (bc of peripheral conversion dopamine to NE), Hypertension, Psychosis (bc of CNS NE increase). Hypotension (dopamine to D1 receptor –vasodilation) Vomiting (D2 receptor in chemoreceptor trigger zone), Dyskinesia (80% after 10 years’ use), and Response fluctuation (after 10 years use)
What is the MOA and ADR of bromocriptine?
Ergot alkaloid D2 agonist, ADRs: hallucinations in elderly
What are the MOA and ADR of pramipexole?
Non ergot D3 agonist that reduces free radical damage (scavenges H2O2), ADR: hallucinations
What are the MOA and ADR of Ropinirole and Selegiline?
MAO B inhibitors, ADRs: may enhance adverse effects of L-dopa, Dyskinesia, psychosis, insomnia.
What are the MOA of tolcapone and entacapone?
inhibit COMT and enhance levodopa uptake and efficacy. In a normal adult, COMT (Catechol-O-Methyltransferase) breaks down L-dopa to 3-O-methyldopa, a less effective metabolite.
Of tolcapone and entacapone, which one is toxic?
Tolcapone because it is hepatotoxic and has both peripheral and central action. Entacapone has only peripheral action and has not such major toxicity.
Why does vitamin B6 increases peripheral metabolism of levodopa?
Vitamin B6 is a cofactor for dopa decarboxylase so it increases peripheral metabolism of levodopa thereby decreasing its effectiveness.
