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Treatment of parknsonism
 

Treatment of parknsonism

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    Treatment of parknsonism Treatment of parknsonism Presentation Transcript

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