Treatment of parknsonism

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Treatment of parknsonism

  1. 1. Treatment of Parkinson’s diseases
  2. 2. <ul><li>Levadopa </li></ul><ul><li>Dopamine agonists (bromocriptine, pergolide, pramipexole). </li></ul><ul><li>MAOI (Selegiline, rasagiline). </li></ul><ul><li>COMT inhibitors ( tolcapone, entacapone) </li></ul><ul><li>Amantadine (antiviral) </li></ul><ul><li>Acetylcholine blocking drugs </li></ul><ul><li>(benztropine) </li></ul>
  3. 4. Levadopa <ul><li>3,4 dihydroxyphenyl-L-alanine </li></ul><ul><li>metabolic precursor of dopamine </li></ul><ul><li>does enter the brai( L. amino acid transpoter, LAT) </li></ul><ul><li>Where it is decarboxylated to dopamine. </li></ul><ul><li>D2 receptor </li></ul><ul><li>Given in combination of Carbidopa (peripheral dopa decarboxylase inhibitor). </li></ul>
  4. 7. <ul><li>Metabolism of levodopa (L-DOPA). ALDH , aldehyde dehydrogenase; COMT , catechol- O -methyltransferase; D H , dopamine  -hydroxylase; AADC , aromatic L-amino acid decarboxylase; MAO, monoamine oxidase. </li></ul>
  5. 8. <ul><li>PK </li></ul><ul><li>Main metabolites </li></ul><ul><li>3- Methoxy-4-hydroxyphenyl acetic acid </li></ul><ul><li>Homovanillic acid, HVA </li></ul><ul><li>Dihydroxyhenylacetic acid ( DOPAC ) </li></ul>
  6. 10. Side effects <ul><li>GI effects- vomiting </li></ul><ul><li>Cardiovascular effects- Postural hypotension, tachycardia, ventricular extrasystole, atrial fibrillation (rare). </li></ul><ul><li>Dyskinesia (prolong therapy) </li></ul><ul><li>Behavioral effects- Depression, anxiety, agitation, insomnia, confusion, changes in mood. </li></ul><ul><li>Drug holidays- discontinue drug 3-21 days ( improve response) </li></ul><ul><li>On-off phenomenon -fluctuation in response </li></ul>
  7. 11. <ul><li>Contraindications </li></ul><ul><li>Angle-closure glaucoma </li></ul><ul><li>Cardiac diseases </li></ul><ul><li>Acid peptic diseases. </li></ul><ul><li>Melanoma </li></ul><ul><li>Interaction- Pyridoxine Vit B6 enhance peripheral metabolism </li></ul>
  8. 12. Levadopa + Carbidopa <ul><li>Sinemet- 25/100 ( carbidopa 25 mg, levadopa 100mg). </li></ul><ul><li>Advantage </li></ul><ul><li>Daily dose req of levadopa dec(75%) </li></ul><ul><li>Less frequent GI effects. </li></ul><ul><li>Less metabolism by pyridoxine. </li></ul>
  9. 13. Dopamine agonists. <ul><li>Bromocriptine (D2 agonist) </li></ul><ul><li>Pramipexole ( not ergot, ) </li></ul><ul><li>Ropinirole </li></ul><ul><li>Rotigine ( skin patches) </li></ul>
  10. 14. <ul><li>Side effects(Dopamine agonist) </li></ul><ul><li>Anorexia, nausea, vomiting (with meals) </li></ul><ul><li>Cardiovascular effects- postural hypotension. </li></ul><ul><li>Dyskinesias - </li></ul><ul><li>Mental disturbance </li></ul><ul><li>Misc- Headache, nasal congestion. </li></ul><ul><li>Contraindication </li></ul><ul><li>Psychotic illness, MI, peptic ulcers </li></ul>
  11. 15. MAOB-Inhibitor <ul><li>Selegiline </li></ul><ul><li>Rasagiline </li></ul>
  12. 16. <ul><li>Selegiline </li></ul><ul><li>Inhibitor MAOB- inhibitor. </li></ul><ul><li>Dec. breakdown of dopamine. </li></ul><ul><li>Selegiline + levadopa </li></ul>
  13. 17. COMT inhibitors <ul><li>Entacapone ( less hepatotoxic) </li></ul><ul><li>Tolcapone </li></ul><ul><li>Adverse effects: </li></ul><ul><li>Dyskinesia, nausea,confusion. </li></ul><ul><li>Diarrhea, abdominal pain, confusion. </li></ul>
  14. 18. Amantadine (antiviral) <ul><li>Antiviral agent </li></ul><ul><li>MOA </li></ul><ul><li>Inhibits dopamine degradation </li></ul><ul><li>Inhibits adenosine that inhibits D2 receptors. </li></ul><ul><li>Less effective than levadopa( iatrogenic dyskinesias) </li></ul><ul><li>S/E - restlessness depression, confusion. </li></ul>
  15. 19. Antimuscarinic drugs <ul><li>Benztropine </li></ul><ul><li>Biperiden </li></ul><ul><li>Orphenadrine </li></ul>
  16. 20. Antimuscarinic drugs <ul><li>MOA </li></ul><ul><li>Antagonists at M receptors in basal ganglia. </li></ul><ul><li>Reduce tremor, rigidity. </li></ul><ul><li>Toxicity: </li></ul><ul><li>Antimuscarinic effects, sedation, mydriasis, urinary retention, dry mouth. </li></ul>

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