Neurodegenerative disorders

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Neurodegenerative disorders

  1. 1. NeurodegenerativeNeurodegenerative DisordersDisorders
  2. 2. ETIOLOGYETIOLOGY • PRIMARYPRIMARY • Also called paralysis agitansAlso called paralysis agitans • HypothesisHypothesis • Absorption of highly potent neurotoxinsAbsorption of highly potent neurotoxins • ManganeseManganese • Carbon monoxideCarbon monoxide • Exposure to free radicalsExposure to free radicals
  3. 3. SECONDARYSECONDARY • PHENOTHIAZINESPHENOTHIAZINES • BUTYROPHENONESBUTYROPHENONES • RESERPINERESERPINE • ENCEPHALITISENCEPHALITIS • METABOLIC DISORDERSMETABOLIC DISORDERS
  4. 4. S/SXS/SX • TREMOR AT RESTTREMOR AT REST • LIMB RIGIDITYLIMB RIGIDITY • AKINESIAAKINESIA • BRADYKINESIABRADYKINESIA • GAIT AND POSTURAL DIFFICULTYGAIT AND POSTURAL DIFFICULTY • RHYTHMIC PILL ROLLING TREMORRHYTHMIC PILL ROLLING TREMOR
  5. 5. • Cogwheel rigidityCogwheel rigidity • Masking of faceMasking of face • Shuffling gaitShuffling gait • MicrographiaMicrographia • Bladder incontinenceBladder incontinence
  6. 6. Stages of Parkinson’s diseaseStages of Parkinson’s disease 0. No clinical signs evident0. No clinical signs evident 1. Unilateral involvement, including the major features of1. Unilateral involvement, including the major features of tremor, rigidity, or bradykinesia; minimal functionaltremor, rigidity, or bradykinesia; minimal functional impairmentimpairment 2. Bilateral involvement but no postural abnormalities2. Bilateral involvement but no postural abnormalities 3. Mild to moderate bilateral disease, mild postural3. Mild to moderate bilateral disease, mild postural imbalance, but still ability to function independentlyimbalance, but still ability to function independently 4. Bilateral involvement with postural instability; patient4. Bilateral involvement with postural instability; patient requires substantial assistancerequires substantial assistance 5. Severe disease; patient restricted to bed or wheelchair5. Severe disease; patient restricted to bed or wheelchair unless aidedunless aided
  7. 7. Drugs Used in Parkinson'sDrugs Used in Parkinson's DiseaseDisease • Start slow – go slowStart slow – go slow • act by counteracting deficiency of dopamine in basalact by counteracting deficiency of dopamine in basal gangliaganglia • by blocking muscarinic receptors.by blocking muscarinic receptors. • LevodopaLevodopa (L-Dopa)sinemet 1:4(L-Dopa)sinemet 1:4 – dopamine precursor that passes BBBdopamine precursor that passes BBB – given with an inhibitor of peripheral dopaminegiven with an inhibitor of peripheral dopamine decarboxylase (e.g.decarboxylase (e.g. carbidopacarbidopa)) – High protein diet causes competition for the drugHigh protein diet causes competition for the drug uptakeuptake – effective in patients but loses efficacy after about 2effective in patients but loses efficacy after about 2 years.years.
  8. 8. Drugs Used in Parkinson'sDrugs Used in Parkinson's DiseaseDisease • Levodopa and Carbidopa (Sinemet)Levodopa and Carbidopa (Sinemet) – First line of drug usedFirst line of drug used – Adverse effectsAdverse effects – Nausea, psychosis, anxietyNausea, psychosis, anxiety – Chronic useChronic use  facial grimacing, jerkingfacial grimacing, jerking – May speed progression of disease (latency ofMay speed progression of disease (latency of disease)disease) – On-Off effectOn-Off effect – Down regulation dosage /drug holidayDown regulation dosage /drug holiday – Antacids – increases absorptionAntacids – increases absorption – MAOIS- Hypertensive crisisMAOIS- Hypertensive crisis – Pyridoxine- co enzyme of carbidopa-decreasesPyridoxine- co enzyme of carbidopa-decreases pharma effectpharma effect
  9. 9. SESE • DECLINING EFFICACYDECLINING EFFICACY • GITGIT • INVOLUNTARY MOVEMENTSINVOLUNTARY MOVEMENTS • TACHYCARDIATACHYCARDIA • ARRHYTMIAARRHYTMIA • POSTURAL HYPOTENSIONPOSTURAL HYPOTENSION • CONFUSSION,DEPRESSIONCONFUSSION,DEPRESSION
  10. 10. Drugs Used in Parkinson'sDrugs Used in Parkinson's DiseaseDisease • AmantadineAmantadine – Increase release of dopamine at nerve terminalsIncrease release of dopamine at nerve terminals – Less efficient than SinemetLess efficient than Sinemet – Restlessness, dry mouth, hallucinationsRestlessness, dry mouth, hallucinations – More rapid reliefMore rapid relief • BromocriptineBromocriptine – agonists of postsynaptic dopamine receptorsagonists of postsynaptic dopamine receptors – added in patients with inadequate response toadded in patients with inadequate response to SinemetSinemet – Inhibit prolactin secretion( used for prolactinomas)Inhibit prolactin secretion( used for prolactinomas) – Pulmonary problems.avoid alcoholPulmonary problems.avoid alcohol
  11. 11. BromocriptineBromocriptine • Ergot derived direct agonist of D2Ergot derived direct agonist of D2 receptorsreceptors • SE: vasoconstriction, PUD, retroperitonialSE: vasoconstriction, PUD, retroperitonial fibrosisfibrosis
  12. 12. • PERGOLIDE – ergot alkaloid agonist atPERGOLIDE – ergot alkaloid agonist at D2D2 • PRAMIPEXOLE – non ergot at D3PRAMIPEXOLE – non ergot at D3 • ROPINIROL – non ergot at D2 and D3ROPINIROL – non ergot at D2 and D3
  13. 13. Drugs Used in Parkinson'sDrugs Used in Parkinson's DiseaseDisease • Selegiline, resagilineSelegiline, resagiline – Irreversible inhibitor of MAO B prevents dopamineIrreversible inhibitor of MAO B prevents dopamine degradationdegradation – Idiopathic parkinsonsIdiopathic parkinsons – Caution in patients with peptic ulcerCaution in patients with peptic ulcer – insomniainsomnia – Increases efficacy of Sinemet and dose reduction ofIncreases efficacy of Sinemet and dose reduction of the drugthe drug – Avoid foods with thiamineAvoid foods with thiamine
  14. 14. • COMTICOMTI • Entacapone , tolcaponeEntacapone , tolcapone • Non- ergot derivatives that increasesNon- ergot derivatives that increases bioavailabity of levodopa in the brainbioavailabity of levodopa in the brain • SE: intense urine color, diarrhea,SE: intense urine color, diarrhea, hepatocellular injuryhepatocellular injury
  15. 15. Drugs Used in Parkinson'sDrugs Used in Parkinson's DiseaseDisease • Benztropine,TrihexyphenidylBenztropine,Trihexyphenidyl – Competitively inhibit postsynaptic muscarinicCompetitively inhibit postsynaptic muscarinic receptorsreceptors – Restores dopamine/acetylcholine balanceRestores dopamine/acetylcholine balance – For tremor treatment with SinemetFor tremor treatment with Sinemet – Adverse effects: sedation,confusion,memoryAdverse effects: sedation,confusion,memory problemsproblems
  16. 16. Neurotransmitter system(s) that may be involved in Parkinson's disease:      A. Dopaminergic      B. Cholinergic  C. both      D. neither
  17. 17. In lower doses, this agent can be used to treat hyperprolactinemia:      A. amantadine      B. levodopa    C. bromocriptine      D. selegiline      E. phenothiazine
  18. 18. Neurological presentations of Parkinsonism EXCEPT:    A. rigidity  B. hyperkinesia    C. tremor      D. postural disturbances
  19. 19. Pharmacological characteristics of L-DOPA    A. not itself pharmacologically active B.  cannot cross the blood-brain barrier C.  can be curative if initiated early enough. D. metabolized only in the brain--due to the presence of a unique dopa-decarboxylase
  20. 20. Anti-Parkinson Drug that probably acts by direct dopamine receptor stimulation     A. benztropine     B.  selegiline  C. bromocriptine     D. amantadine

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