Drugs for Neurodegenerative Diseases Wikispaces药物对神经退行性疾病 wiki空间.pptxVIP

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Drugs for Neurodegenerative Diseases Wikispaces药物对神经退行性疾病 wiki空间.pptx

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Drugs for Neurodegenerative Diseases Kaukab Azim, MBBS, PhD Drug List Drugs for Parkinson’s Disease Drugs that increase brain dopamine levels Dopamine receptor agonists M receptor antagonists Levodopa Carbidopa Selegiline Entacapone Amantadine Bromocriptine Pramipexole Benztropine Drugs for Huntington’s Disease Drugs for Alzheimer’s Disease Haloperidol* Diazepam* Donepezil Learning Outcomes By the end of the course the students will be able to Explain the mechanism of action of each drug in each group Describe the main effects of each drug on different organ systems Describe the absorption, distribution and metabolism of levodopa and carbidopa Describe the administration routes of each drug in each class Describe the main adverse effects of each drug in each class Explain the on/off effect and wearing-off effect of levodopa / carbidopa Explain the therapeutic value of combining levodopa with carbidopa in Parkinson’s disease Explain the use of dopamine agonists and antimuscarinic drugs in Parkinson’s disease Explain the use of neuroleptic and benzodiazepines in Huntington’s disease Explain the use of central cholinesterase inhibitors in Alzheimer’s disease Levodopa Chemistry The amino acid levodopa is the biosynthetic precursor of dopamine. Mechanism of action In the brain levodopa is taken up by dopaminergic terminals in the striatum and is converted to dopamine by levo-aromatic amino acid decarboxylase (LAAD) (dopamine as such cannot be used since it does not enter the brain). Levodopa itself is largely inert. Its effects depend on the increased synthesis of dopamine in the brain and are mostly related to activation of D2 receptors. Medulla Glucocorticoid + Levodopa Pharmacological effects The peripheral effects of levodopa are related to the plasma concentration of dopamine. Pharmacokinetics Oral bioavailability: 5% (the firs-pass effect is very large; 95% is metabolized in the gut wall and in the liver) Additional amounts are converted into dopamine and therefor