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بسم الله الرحمن الرحيم

بسم الله الرحمن الرحيم. ANTI-PARKINSONISM Dr: Samah Gaafar Al- shaygi. Parkinson Disease. Neurodegenerative diseases. Dopamenergic neurones in substantia nigra . Environmental* genetic factors. Resting tremor, muscular rgidity & bradykinesia . Secondary parkinsonism.

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بسم الله الرحمن الرحيم

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  1. بسم الله الرحمن الرحيم ANTI-PARKINSONISM Dr: SamahGaafar Al-shaygi

  2. Parkinson Disease • Neurodegenerative diseases. • Dopamenergicneurones in substantianigra. • Environmental* genetic factors. • Resting tremor, muscular rgidity & bradykinesia. • Secondary parkinsonism.

  3. Therapy aim is to • minimize disability and side effects while maintaining quality of life. • restore dopamine in the basal ganglia & antagonize ACH. • The drugs are almost palliative ones.

  4. Drugs used in parkinsonDx • Levodopa & Carpidopa. • L-dopa is a dopamine precursor. • Very effective in the beginning of the dx. • Carpidopa a dopadecarboxylase inhibitor. • Decrease the dose of L-dopa needed (*4-5). • Decrease side effects.

  5. Absorption & metabolism: • On empty stomach 45min before a meal. • L-dopa is rapidly absorbed from the GIT. • is absorbed primarily in the proximal duodenum by a saturable large neutral amino acid (LNAA) transport system. (Competition) • Has short ½ life (1-2hrs). • not bound to plasma proteins. • It crosses the blood-brain barrier by saturable facilitated diffusion and competes with LNAA for transport into the brain.

  6. ADVERSE EEFECTS: • Peripheral effects: • N&V. • Tachycardia & hypotension. • Mydriasis. • Brownish urine & saliva. • CNS: anxiety, psychosis, depression. • Wearing off. • Dyskinesias and dystonias.

  7. Selegiline: • MAO-B inhibitor. • Lipophilic. • Reduces L-dopa dose. • Metabolized to amphetamine (insomnia). • COMT-inhibitors: • L-dopa COMT 3-O-methyl dopa (competes with L-dopa for brain transport). • Entacapone reduces wearing off phenomena.

  8. Pharmacokinetics: • Plasma protein bound >98%. • Metabolized & excreted hepatically & renally. • Adverse effects: • Diarrhea, postural hypotension, sleep disorders. • Fulminant hepatic necrosis (tolcapone).

  9. Dopamine-receptor agonists: • In advanced dx with motor fluctuation & dyskinesia. • Have no effects on non-responders to L-dopa. • Bromocreptine.more nausea, hallucinations & less dyskinesias. • Worsen MI, perepheral vascular dx, pulmonary fibrosis. • Apomorphine as injections in advanced dx. • Delay the need for L-dopa in early parkinson & decrease the L-dopa dose in advanced dx. • No worsening of vasospasm & no fibrosis.

  10. Amanitidine: • An anti-viral drug. • Increases the release of dopamine & blocks the cholinergic receptors. • Less effective than L-dopa & readily developed tolerance. • Restlessness, hallucinations, toxic psychosis. • Little effect on tremor butmore the anticholinergic on rigidity & bradykinesia.

  11. Antimuscarinic agents: • Only adjuvant role. • Benztropin, procyclidine. • S.E: mood changes, xerostomia, urinary retention tachycardia. • Contraindicated in glucoma, BPH & pyloric stenosis.

  12. Thank you

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