Parkinsonism drugs

Parkinsonism drugs

Drugs aim to restore balance between the neurotransmitters acetylcholine and dopamine in the CNS.

1) Drugs that increase dopaminergic activity:
• eg Levadopa, amantadine, bromocriptine, levadopa-carbidopa
• increase amount of dopamine available in CNS or enhance the neurotransmission of dopamine
• dopamine can not cross blood-brain barrier
• Levadopa (precursor of dopamine)  restores dopamine levels by being converted by enzymes to dopamine
• drug of choice (75% get 50% reduction in symptoms) – full response takes 2-3 months, but after 5 years less effective
• crosses blood-brain by active transport, then taken up into remaining dopaminergic nerve terminal in the striatum  converted to dopamine
• administered orally; absorbed rapidly by GI tract; only small amount reaches brain (metabolised by decarboxylase enzymes)
• effectiveness reduced when used with vitamin B6, phenytoin or benzodiazepines; MAO inhibitors increase risk for hypertension.
• contraindications – narrow angle glaucoma;
• adverse effects – nausea and vomiting (especially early), orthostatic hypertension, involuntary movements of limbs and face (dyskinesia), hallucinations and other psychiatric effects (common reason for limiting use).
• Carbidopa
• marketed in combination form with levodopa
• enhances effects of levadopa by inhibiting the effects of decarboxylase enzymes
• does not cross blood brain barrier, so acts peripherally to reduce metabolism  increases amount reaching brain
• Amantadine  promotes release of dopamine from remaining dopaminergic terminals  increases the amount dopamine
• Antiviral drug with dopaminergic activity
• adverse effects – dizziness, confusion, mood changes

2) Central anti-cholinergic drugs:
Relieve symptoms by blocking cholinergic receptors in the striatum  inhibit action of acetylcholine
Less commonly used.

eg benztropine, trihexyphenidyl

Gait analysis  drug effectiveness

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