Parkinson's Disease

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Author:
trincam2008
ID:
296550
Filename:
Parkinson's Disease
Updated:
2015-02-22 20:14:38
Tags:
Parkinsons
Folders:
PSA
Description:
Parkinsons - 23/2/15
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  1. MAO-A/Bi and COMT
    • Monoamine oxidase inhibitor
    • Catechol-o-methyl transferase
  2. Chemical hypothesis for rational therapy
    Parkinson's is due to dopamine deficiency in the basal ganglia, medulla and hypothalamus
  3. Drugs types - broad reminder
    • 1. Historical use/specific indications
    • 2. Dopamine-based treatments
    • 3. Adjuncts/alternative to dopamine therapy
    • 4. Dopamin agonists
  4. Drugs types - broad + classes:
    1. Historical use/specific indications
    • a) Anti-cholinergic e.g. procyclidine
    • b) Amantadine
    • (1 ng đàn ông thay tả nhảy múa: amantadine - dyskineasias)

  5. Drug type - 2. Dopamine-based treatments
    - 1st line: Levodopa + decarboxylase inhibitors  - S.e
  6. Drug type - 3. Adjuncts/alternative to dopamine therapy
    • Rationale:
    • as dopamine is metabolised into MAO-B and COMT) 

    • a) MAO-B inhibitors: selegiline, rasagiline 
    • (mao mao mèo ra sàn xê lên (xê xuống) chơi với gỉ lin - len: rasagiline, selegiline)

    • b) COMT inhibitors: entacapone
    • (COMT cái lược cầm tay enta capone (carpal bone)
  7. Drug type - 4. Dopamine agonists
    • a) Ergot derivatives: Bromocriptine, Lisuride,
    • Cabergoline 
    • (ergot giun màu đà brom mô bò bò criptine, li trong như sứa lisuride, cá bơi gỗ lin cabergoline)

    • b) Synthetic derivatives: Ropinirole, pramipexole 
    • (tổng hợp synthetic: dây rộp hòn bi nì, rộP cành rami cột lại pex)

    • c) Apomorphine
    • (potent - apo - morphine)
  8. Drug use - 1.a. anti-cholingergic
    - young pt with mild PD and tremor as main feature

    - s.e muscarinic and CNS effects (confusioin, hallucinations, memory deficits)
  9. Drug use 1b Amantadine
    • - Mechanism unknown
    • - mild/moderate disease and late disease w/ Dyskinesia
  10. Levodopa use
    - A pro drug of dopamine - converted to dopamine by dopa-decarboxylase once it has crossed the BB barrier

    • - 1st line therapy but prob w/ when to start
    • - Requires slow titration

    • - Should always be co-administered w/ decarboxylase inhibitors e.g. carbidopa/benserazide
    • (đi cùng cả bì dopa carbidopa)
  11. Levodopa side effects - short term
    • - Nausea / vomitting -> domperidone
    • - Diarrhoea/constipation (chieu nguoc)
    • (GI)
    • (Cardio)
    • - Postural hypotension
    • - Haemolytic anaemia
    • - Cardiac arrhythmias
  12. Levodopa - long term s.e
    • - Neuropsychiatric syndromes (delirium, hallucinations, psychosis)
    • => dose reduction, atypical antipsychotic e.g. clozapine

    • - Fluctuations in response e.g. end of dose akinesia, peak dose dyskinesia, on-off response
    • => precise regulation of blood level

    • - Loss of response 50% at pre-treatment level by 5 years
    • => Da agonist, new therapies stem cells?
  13. MAO-B inhibitors
    • Selegiline
    • - Selective MAO-Bi
    • - Used together with levodopa - can reduce dose related response fluctuation and absolute dose needed 
    • - BUCCAL preparation

    • S.e.
    • - Potentiates DOPA-symptoms
    • - sleep disturbance (due to metabolism to amphetamine)
    • (mèo chạy lung tun ko ngủ, ngậm miệng)

    - Rasagiline

    - Selective. fewer s.e
  14. COMT
    • - levo sparing (20%)
    • - longer effects prolongs actions of a single dose
  15. Dopamine agonist - potential roles
    • - loss of levodopa response
    • - response fluctuation
    • - severe dyskinesia
    • - 1st line therapy as a levodopa - sparing agent
  16. Dopamine agonists - 3 families, advantages
    • a. Bromocriptine, lisuride, cabergoline
    • - Less effective than levodopa but fewer late unwated dyskinesia
    • (giun ít bò hơn)

    • b. Ropinirole, pramipexole
    • - delay need to start levo-dopa. S.e. less severe but may cause sleep attacks

    • c. Apomorphine
    • - Very potent D1 and D2 agonist. Used in Parkinsonian emergencies and on-off response
    • - Severe nausea
  17. S.E due to non-dopamine ergot base
    • - GI: nausea
    • - Vasospasm
    • - Fibrosis (pleural, pericardial, retroperitoneal, heart valves (R>L)
  18. Medical Mx of PD - young fit, frail & comorbidities
    • - Young onset + biologically fit
    •  + Da agonists (trẻ leo cây) ropinirole, pramipexole
    •  + MAO-B inhibitor: selegiline, rasagiline
    •  + L-dopa: co-careldopa or co-beneldopa (co - chăm sóc & hưởng benefit)

    • - Frail +- comorbidities
    •   + L-dopa
    •   + MAO-B
  19. Medical - Response fluctuations
    • (ADa agonists)
    • - MAO-B inhibitor
    •   + ↓ end-of-dose effects
    • - COMT inhibitor: endocapone, tolcapone
    •   + Lessen off time @ end of dose
    • (Da agonist)
    • - Apomorphine:
    •   + rescue pen for sudden off freezing
    • - Amantadine:
    •   + weak, Rx of drug-induced dyskinesias

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