(B) (Inhibit peripheral decarboxylation of levodopa) (429-30 KDT 7th) (Lippincott's Pharmacology)Carbidopa is combined with levodopa to inhibit peripheral decarboxylation of levodopa and make more levodopa available to cross the blood brain barrier to reach its site of action.Extracerebral Dopa Decarboxylase inhibitorsCarbidopaQBenserazideQCo-administration of levodopa with peripheral Decarboxylase inhibitors :* Levodopa is a metabolic precursor of dopamine and is the first- line treatment for Parkinson's disease (PD) is believed to result from insufficient dopamine in specific regions of the brain)* Dopamine itself does not cross the blood brain barrier but levodopa (its immediate precursor) is actively transported in to the CNS and is converted into dopamine in the brain* The major limitation of Levodopa however is that large amount of Levodopa is decarboxylated in the peripheral tissue forming dopamine in the periphery (this dopamine formed in the periphery does not cross blood brain barrier).* Asa result large amount of Levodopa are required to obtain the desired therapeutic effect and side effects from formation of dopamine in the periphery like nausea, vomiting, cardiac arrhythmias and hypotension become prominent.* Lovodopa is therefore usually coadministerd with peripheral decarboxylase inhibitors like carbidopa or Benserazide which prevent the decarboxylation of leyodopa in peripheral tissues there by making more levodpa available to act on the CNS.* These peripheral decarboxylase inhibitors do not penetrate the blood brain barrier and hence do not inhibit conversion of levodopa to dopamine in the brain which is required for its therapeutic action.* Levodopa for these reasons is almost always coadministered with a peripheral decarboxylase inhibitor like carbidopa or benserazide.Benefits of Co-administering Lavodopa with Carbidopa/Bensersazide* Prolongs the plasma t'A of levodopa and reduces the dose needed to approximately 1/4th* Reduces the peripheral side effects of levodopa as the concentration of dopamine in the peripheral tissues reduced- | Nausea and vomiting- | Cardiac complication* May reduce the on- off effect since cerebral dopamine levels are more sustainedRapid fluctuations in clinical state where' hypokinesia and rigidity suddenly worsen and then improve again is called the on off effect. This on- effect is not seen in untreated patients with PD but are known unwanted effects of levodopa therapy* Degree of improvement may be higher as some patients not responding to levodopa alone also improve* Co-administration with carbidopa, however does not resolve all unwanted effectsProblems not resolved by coadministration of carbidopa include* Involuntary movements/Behavioral abnormalities* Postural hvpotension Synthesis of Dopamine from Levodopa in the absence and presence of carbidopa, an inhibitor of dopamine decarboxylase in the peripheral tissue.