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What is In treatment of parkinsonism, L-Dopa is combined with carbidopa mainly and explain in detail?
Ans. d. (To make more of L-Dopa available to cross the blood brain barrier) (Ref. KDT 6th/418.)# Carbidopa & Benserazide are peripheral Decarboxylase inhibitor.# When administrated with L-dopa, they increase peripheral half-life of L-dopa & make more of it available to cross blood brain barrier.LEVODOPA# Levodopa is rapidly absorbed from the small intestine, but its absorption depends on the rate of gastric emptying and the pH of the gastric contents.# Food will delay the appearance of levodopa in the plasma.# Plasma concentrations usually peak between 1 and 2 hours after an oral dose, and the plasma half-life is usually between 1 and 3 hours, although it varies considerably between individuals.# Unfortunately, only about 1-3% of administered levodopa actually enters the brain unaltered, the remainder being metabolized extracerebrally, predominantly by decarboxylation to dopamine, which does not penetrate the blood-brain barrier.# This means that levodopa must be given in large amounts when it is used alone.# However, when it is given in combination with a dopa decarboxylase inhibitor that does not penetrate the blood- brain barrier, the peripheral metabolism of levodopa is reduced, plasma levels of levodopa are higher, plasma half-life is longer, and more dopa is available for entry into the brain.# Indeed, concomitant administration of a peripheral dopa decarboxylase inhibitor may reduce the daily requirements of levodopa by approximately 75%.