Tuesday, October 13, 2015

Study group discussion: Pharmacology of drugs used in Parkinsons disease

Why does bradykinesia and rigidity occur in Parkinson's disease?

Bradykinesia is due to deficiency of dopamine.
Rigidity is due to uncompensated increase in acetylcholine.

Why levodopa is always given in combination with carbidopa and entacapone? 

Carbidopa is given to protect levodopa against dopa decarboxylase enzyme which causes its peripheral breakdown. Peripheral conversion of dopamine is harmful.. Can cause cardiac arrhythmias and postural hypotension.

Entacapone is given to block COMT.

Difference between entcapone and talcapone?

Entcapone can't enter the CNS. Inhibits only peripheral COMT.
Tolcapone prevents L-dopa degradation in the brain as well as the periphery.
Mnemonic: http://medicowesome.blogspot.in/2014/03/antiparkinsonism-drugs-mechanism.html

Tolcapone crosses BBB. And is toxic to liver
Tol = tall (can reach brain)
toL = L ( liver toxicity)
Tall and long = Long half life

What are the other drug beside COMT and dope decarboxylase drug can we give to inhibit peripheral breakdown of levodopa?

MAO B inhibitors like Selegiline, Rasagiline.

What the difference between Selegiline and Rasagiline?

Selegiline is metabolized to amphetamine and methamphetamine.
Rasagiline's major metabolite is amioindan, which has no amphetamine-like properties.

Selegiline losses it's selectivity for MAO at high dose.

Related post: Management of Parkinson's disease

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