PM 719 Pharmacology II Levodopa Study Notes PDF

PM 719 Pharmacology II Seven Things (ST) Document Spring 2025 C28 Parkinsonism **Levodopa** \(1) Drug Class and Stem: Anti-Parkinsonism drug, a precursor of the neurotransmitter dopamine (DA) DA will not cross the BBB, Levodopa will enter the CNS and be enzymatically converted in the brain to...

PM 719 Pharmacology II Seven Things (ST) Document Spring 2025 C28 Parkinsonism **Levodopa** \(1) Drug Class and Stem: Anti-Parkinsonism drug, a precursor of the neurotransmitter dopamine (DA) DA will not cross the BBB, Levodopa will enter the CNS and be enzymatically converted in the brain to DA. The enzymatic reaction results in decarboxylation of \(2) Primary Clinical Use: Replace the lost DA in the substantia nigra which is the characteristic pathological \(3) Site of Action and Receptor(s): There are multiple subtypes of the DA receptors in the brain. Levodopa when converted to DA binds mostly to D~1~ and D~2~ receptors. Binding of DA to these DA receptors causes potassium to flow out of the neuron which causes inhibition of the neuronal actions. \(4) Mechanism of Action: Replace DA in the CNS and restore normal motor functions. \(5) Physiological Effects: The drugs are designed to reduce the major clinical symptoms of Parkinsonism which are, rigidity, bradykinesia, tremor, and postural instability. Tremor at rest is a hallmark of Parkinsonism. \(6) Major ADRs: Levodopa after 3-4 years the benefits of this drug are diminished for reasons not well understood. Patients are taken off the drug for different periods of time to slow down the loss of efficacy of the drug levodopa. \(a) GI: About 80% of patients experience anorexia, vomiting and nausea when levodopa without the cardidopa enzyme inhibitor, but reduced to about 20% when combination drugs is given. Cardipoda nhibits the enzyme in the PNS called dopa decarboxylase. This enzyme converts levodopa to DA which then cannot enter the CNS. \(b) Cardiovascular Cardiac arrhythmias often but reduced when combination drug is administered. \(c) Behavioral Effects The combination drug increases the DA levels in the brain and behavioral changes are more common when levodopa alone is given. These changes include depression, anxiety, insomnia, somnolence, and euphoria. \(d) Dyskinesias and Response Fluctuations Dyskinesia in up to 80% of patients in those on the drug for more than 10 years Choreoathetosis of the face and distal extremities are most common. Drug Holiday Stop the drug levodopa for 3-21 months which helps reduce the ADRs and improve the drug response when the drug is re-started Vitamin B6 enhances the peripheral biotransformation of levodopa. This problem is reduced when combination drug is used \(7) Modes of Administration: PO tablets, absorption is delayed when food is present. Half-life is about 1-3 hours Levodopa combined with a dopa decarboxylase inhibitor which prevents the bioconversion of levodopa to DA in the peripheral nervous system which would never enter the CNS. Combination levodopa + carbidopa = replacement of DA + dopa decarboxylase inhibitor