Parkinson's Drugs

• Tremor at Rest (pill rolling)
• Rigidity (cogwheel stiffness)
• Akinesia or Bradykinesia
• Postural instability with gait problems

• Depression
• Anxiety or Panic
• Apathy

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

• Idiopathic (85)
• Post-Encephalitic
• Genetic
• Environmental Toxicity
• Cerebral Atherosclerosis
• Iatrogenic

Drugs that block D2 receptors:

• Phenothiazines (Chlorpromazine)
• Butyrophenones (haloperidol)
• Metoclopramide

• 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

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

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

• 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

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

Unpredictable response to drugs

• Confusion
• Psychosis
• Hallucinations
• Dyskinesias  (Choreiform, ballistic and dystonic movements)

• Dysrhythmias
• Orthostatic hypotension
• Nausea and Vomiting

• Pyridoxine
• D2 Antagonists
• Anticholinergics
• Non-specific MAO inhibitors

• Psychotic Disorders
• Angle Closure Glaucoma
• Malgnant Melanoma
• Previous history of dysrhythmias

• 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

• Side Effects
• Similar to L-Dopa
• Greater psychiatric effects
• Lesser Dyskinesias
• First dose syncope

• Other Uses
• Acromegaly
• Hyperprolactinema
• Restless legs syndrome

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)

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

• Myoclonus
• Rigidity
• Confusion
• Autonomic instability

leads to coma and death

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