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Drugs for PD

Drugs for Parkinson's Disease

Parkinson's disease: signs and symptoms Tremors at rest, rigidity, postural instability, bradykinesia
Levodopa: minimizing gradual loss 1. Shortening dosing interval 2. Give drug that prolong levodopa's plasma half life (like entacapone) 3. Give direct acting dopamine agonist
Levodopa: minimizing abrupt loss of effects Entacapone and Rasagiline
Levodopa: mechanism of action Increases synthesis of dopamine in striatum (enters brain where it is converted to dopamine in active form by decarboxylase)
Levodopa: adverse effect (major one) Dyskinesia
Levodopa: adverse effects Postural hypotension, psychosis, N/V, darken urine and sweat
Levodopa: adverse effects (CV) Dysrhythmia in patients with heart disease
Levodopa: minimizing psychosis effects 1. Reduce levodopa dosage 2. Clozapine and quetiapine (second generation antipsychotics, does not block dopamine)
Levodopa: drug interactions that decreases effects of levodopa First generation antipsychotics (chlorpromazine, halperidol) from dopamine blockade
Levodopa: drug interactions with MAO inhibitors Causes hypertensive crisis
Levodopa: contraindications Nonselective MAO inhibitors (must be withdrawn at least 2 weeks prior)
Levodopa: drug interactions that increase effects of levodopa Anticholinergic drugs
Levodopa: drug interactions with pyridoxine (vitamin B6) Stimulates decarboxylation of levodopa, which reduces its effects
Levodopa: food interactions High protein meals reduces therapeutic effects
Levodopa/Carbidopa: mechanism of action Used to enhance effects of levodopa. Inhibits decarboxylation of levodopa
Dopamine agonists:nonergot derivatives Pramipexole, ropinirole, apomorphine. More selective for dopamine receptors. Causes less side effects and are preferred
Dopamine agonists: ergot derivatives Bromocriptine and carbergoline. Less selective for dopamine receptors. Causes more side effects
Dopamine agonists: advantages Not dependent on enzymatic conversions to become active. Does not compete with protein for uptake and blood brain transport. Lower incidence of response failure. Less likely to cause disabling dyskinesia
Dopamine agonists: disavantages More serious side effects -- especially hallucinations, daytime sleepiness, postural hypotension. Should be reserved for younger patients
Pramipexole: mechanism of action Nonergot dopamine agonist. Binds selectively to D2 and D3 receptors
Pramipexole: uses Used alone in early stage PD and combined with levodopa in advanced stage PD. Also approved for moderate to severe restless leg syndrome
Pramipexole: adverse effects (unique) Sleep attacks and impulse control disorder
Pramipexole: adverse effects (used alone) Nausea, dizziness, daytime somnolence, insomnia
Pramipexole: adverse effects (combined with levodopa) Orthostatic hypotension, dyskinesia, hallucination
Pramipexole: drug interactions that increases pramipexole levels Cimetidine (drug for peptic ulcer) inhibits excretion of pramipexole
Entacapone: mechanism of action COMT inhibitor, prolonging half life of levodopa and decreases production of levodopa metabolites that competes with levodopa for blood brain transport
Entacapone: adverse effects (used alone) Yellow-orange urine, vomiting, diarrhea, constipation
Entacapone: adverse effects (combined with levodopa) Dyskinesia, orthostatic hypotension, hallucination, impulse control disorder, sleep disturbances, nausea
Entacapone: drug interactions Increases levels of drugs that are metabolized by COMT. Includes levodopa, methyldopa, dobutamine, isoproternol
Selegiline: mechanism of action MAO-B inhibitor, prolongs effects of levodopa and may delay progression of PD
Selegiline: pharmacokinetics Two metabolites that can cause harmful effects
Selegiline: adverse effects Insomnia
Selegiline: adverse effects (high doses) Inhibits MAO-A inhibitors, increasing risk for hypertensive crisis
Selegiline: drug interactions (combined with levodopa) Intensifies adverse effects of levodopa (orthostatic hypotension, dyskinesia, hallucinations)
Selegiline: drug interaction Meripidine cauases stupor, rigidity. Fluoxetine is fatal
Created by: suezy



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