Parkinson's Drugs

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Author:
jncates
ID:
209998
Filename:
Parkinson's Drugs
Updated:
2013-03-28 11:33:03
Tags:
CNS Drugs Parkinson
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Description:
Drugs used in treatment of Parkinson's Disease
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  1. Motor Symptoms in Parkinson's Disease
    • Tremor at Rest (pill rolling)
    • Rigidity (cogwheel stiffness)
    • Akinesia or Bradykinesia
    • Postural instability with gait problems
  2. Non-Motor symptoms in Parkinson's
    • Depression
    • Anxiety or Panic
    • Apathy
  3. Mechanism of Parkinson's Disease
    Not enough dopamine from the nigrostriatal pathway leads to a decreased inhibition of the striatum (increased amount of ACh activation) which leads to impaired control of movement
  4. Causes of Parkinson's Disease
    • Idiopathic (85)
    • Post-Encephalitic
    • Genetic
    • Environmental Toxicity
    • Cerebral Atherosclerosis
    • Iatrogenic
  5. Drugs with side effects that mimic Parkinson's
    Drugs that block D2 receptors:

    • Phenothiazines (Chlorpromazine)
    • Butyrophenones (haloperidol)
    • Metoclopramide
  6. Stages of Parkinson's
    • Early- No functional impairment
    • Mild - honeymoon period - all drugs work in this period
    • Moderate - multiple drugs, occupational and social activities are affected
    • Severe - Side effects from drugs, resistant to therapy, reduced quality of life
    • Late - wheelchair or bed bound
  7. L-Dopa Therapy
    Increases amount of Dopamine in the substantia Nigra since it is a precursor for Dopamine

    • big treatment for bradykinesia and rigidity
    • also big for elevating mood
    • mild treatment for tremor
    • not much treatment for posture or gait
  8. L-Dopa metabolism
    L-Dopa crosses the BBB whereas Dopamine doesnt

    • L-Dopa can be converted to dopamine or 3-OMD by AAAD or COMT respectively
    • Dopamine is converted to NE and Inactive metabolites by DBH and MAO-B

    • Carbidopa inhibits AAAD in the periphery
    • Tolcapone inhibits COMT in the periphery and central 
    • Selegiline inhibits MAO-B
  9. Carbidopa
    • inhibits peripheral AAAD
    • increases apparent potency of L-Dopa
    • decreases the peripheral side effects of the L-Dopa
    • better control of L-dopa concentration which evens out the fluctuations
    • Prevents Vitamin B6 antagonism of L-Dopa
  10. Tolcapone or Entacapone
    Prevents Degradation of L-Dopa by COMT

    •  ⋅Reduces 3-OMD
    •  ⋅Allows lower doses of L-Dopa
    •  ⋅Reduces end of dose deterioration and motor fluctuations

    toxic effect - acute hepatic necrosis
  11. Late stage complications of Parkinson's disease and treatment
    Unpredictable response to drugs
  12. Side effects of L-Dopa
    CNS
    • Confusion
    • Psychosis
    • Hallucinations
    • Dyskinesias  (Choreiform, ballistic and dystonic movements)
  13. Side effects of L-Dopa
    Cardio and GI
    • Dysrhythmias
    • Orthostatic hypotension
    • Nausea and Vomiting
  14. Drug Interactions with L-Dopa
    • Pyridoxine
    • D2 Antagonists
    • Anticholinergics
    • Non-specific MAO inhibitors
  15. Contraindications for L-Dopa therapy
    • Psychotic Disorders
    • Angle Closure Glaucoma
    • Malgnant Melanoma
    • Previous history of dysrhythmias
  16. Dopamine Agonists
    Drugs, Uses, Action
    • Bromocriptine
    • Pramipexole
    • Ropinirole

    Directly stimulate D2 receptors

    • Reduces motor fluctuations
    • Improves motor function
    • Allows lower L-Dopa doses

    • early PD - minimizes wearing off
    • Late PD - as dopaminergic neurons degenerate
  17. Dopamine Agonists
    Side Effects and Other Uses
    • Side Effects
    • Similar to L-Dopa
    • Greater psychiatric effects
    • Lesser Dyskinesias
    • First dose syncope

    • Other Uses
    • Acromegaly
    • Hyperprolactinema
    • Restless legs syndrome
  18. Dopamine Releasing Agent
    Amantadine

    Enhances release of dopamine

    treats tremor, bradykinesia, rigidity and dyskinesias

    • early PD as a monotherapy
    • moderate PD as an adjunct to L-Dopa

    • Side Effects
    • CNS - insomnia
    • Livedo Reticularis (blue-reddish skin discoloration)
  19. MAO-B inhibitor
    Selegiline and Rasagiline

    • extends duration of L-Dopa action
    • allows reduction of dose
    • reduces motor fluctuations

    neuroprotective

    • Side Effects
    • Insomnia

    • Drug Interactions
    • Serotonin Reuptake inhibitors: TCA and SSRI, Meperidine
  20. Serotonin Syndrome
    • Myoclonus
    • Rigidity
    • Confusion
    • Autonomic instability

    leads to coma and death
  21. Antimuscarinic Agents used in Parkinsons
    Benztropine mesylate, diphenhydramine, trihexyphenidyl

    Blocks central postsynaptic muscarinic receptors

    reduces tremor and rigidity

    doesnt improve bradykinesia

    • Side Effects
    • Predictable based on the antimuscarinics
    • Contraindications
    • Angle Closure Glaucoma
    • other drugs with antimuscarinic side effects

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