1. ANTI- PARKINSONISM Dr: Samah Gaafar Al-shaygi

2.  Neurodegenerative diseases.  Dopamenergic neurones in substantia nigra.  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. 1. Levodopa & Carpidopa.  L-dopa is a dopamine precursor.  Very effective in the beginning of the dx.  Carpidopa a dopa decarboxylase inhibitor. 1. Decrease the dose of L-dopa needed (*4-5). 2. 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: 1. Peripheral effects:  N&V.  Tachycardia & hypotension.  Mydriasis.  Brownish urine & saliva. 2. CNS: anxiety, psychosis, depression. 3. Wearing off. 4. 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