Flashcards in Parkinson's Drugs Deck (11):
The next set of drugs for Parkinson's Disease are the inhibitors for Dopamine Metabolism. First up are the MAOI. First is selegiline (deprenyl). What are some features?
Inhibits MAO-B (which selectively metabolizes dopamine)
--retards the breakdown of dopamine in the brain this enhances the effect of levodopa and allows the dose of levodopa to be reduced
Mainly used as adjunctive therapy for patients with a declining or fluctuating response to levodopa
Metabolized to methamphetamine and amphetamine
The other MAOI used is Rasagiline. What are some features?
Used for early symptomatic treatment
--also adjunctive therapy to prolong effects of levodopa-carbidopa in patients with advanced disease
Next set of drugs for Inhibitors of Dopamine Metabolism are COMT (catechol-o-methyltransferase inhibitors). COMT is responsible for the catabolism of levodopa as well as a dopamine. The inhibition of COMT is via Tolcapone and Entacapone. What are some features?
Inhibition of dopa carboxylase leads to compensatory activation of other pathways of levodopa, esp COMT and this increases plasma levels of 3-O-methyldopa (3-O-MD)
--3-O-MD competes with levodopa for a carrier that governs its transport across the intestinal mucosa and the blood brain barrier
Inhibition of COMT by tolcapone and entacapone leads to decreased metabolism of levodopa, decreased plasma levels of 3-O-methyldopa, increased uptake of levodopa and higher concentrations of dopamine in the brain.
Tolcapone and Entacapone, are similar and both are rapidly absorbed, bound to plasma proteins and metabolized prior to excretion. However, how are they different?
Tolcapone: has both central and peripheral effects, whereas the effect of entacapone is only peripheral
Entacapone: preferred because it has not been associated with hepatotoxicity
Entacapone is only available as fixed dose combo with levodopa/carbidopa
What are the Adverse Effects of the COMT inhibitors?
Fulminating hepatic necrosis (tolcapone)
--use requires monitoring of liver function tests every 2 weeks
The antiviral drug Amantadine also has antiparkinsoniam actions, how?
It appears to increase synthesis, release or re-uptake of dopamine from the surviving neurons
What is the major side effect of Amantadine?
--usually clears within a month after withdrawing the drug
Finally Anti-muscarinics can be used. Benztropine Mesylate and Trihexyphenidyl. What are some features of these drugs?
--improve tremor, rigidity and drooling but have little effect on bradykinesia
--Interfere with GI peristalsis and are contraindicated in patients with glaucoma, prostatic hypertrophy or pyloric stenosis
What is the most effective symptomatic treatment for Parkinson's Disease?
Levodopa combined with carbidopa
--dopamine agonists are the next most effective drugs after levodopa (can be used alone or in adjunct with levodopa) and the non ergot dopamine agonists are preferred
Addition of a COMT inhibitor or MAO-B inhibitor to levodopa does what?
Can reduce motor fluctuations in patients with advanced disease