Anti-Parkinson Drugs

Dr Gareth Noble

Aims

To review pathogenesis of Parkinson's

To review clinical presentation To identify treatment drugs

Parkinsons Disease

A degenerative , decreased dopamine substantia nigra =to corpus striatum (controls unconscious muscle)

Treatment (early stage)

based upon level of disability, age, cognitive status, concurrent medial problems

Levodopa determine optimal dose

Treatment (maintenance stage)

Speech therapist swallowing problems sleep thermoregulation beta-blockers

Treatment (complex stage) Combine drugs DRACHD

Dyskinesias and Dystonia =co-beneldopa Restless-leg dopamine agonists Anxiety relaxation, distraction, Cognitive problems psychologist antidementia Hallucinations - anti-psychotics Depression alter dose

Medication Rational

Replace Increase effect dopamine Stimulate neurotransmission Counteract Ach

Drugs:

Dopaminergic drugs

Levodopa Dopamine receptor agonists Amantadine Selective monoamine oxidase B inhibitors Catechol-O-methyltransferase inhibitors

Antimuscarinic drugs (Ach inhibitors)

Levodopa (Madopar & Sinemet)

dopamine not cross the blood brain barrier slow release, to co-beneldopa or co-careldopa (Sinemet) Dose = 50, 100 or 200mg (12.5, 25 or 50mg)

Pharmacokinetics:

Absorbed active Decarboxylation peripheral Short half-life

Adverse effects

peripheral

Nausea Postural hypotension Dyskinetic Hallucinations

CNS

Dopamine receptor agonists

Apopmorphine :

Rescue therapy rapid short (~50mins)

Bromocriptine; Pergolide; Ropinirole brain dopamine receptors

?longer that Levodopa

Start alone, then levodopa smooth out Pharmacokinetics:

extensive first-pass metabolism (biotransformed in liver) medium half life.

Adverse effects:

N + V (particularly Apomorphine) Dyskinesia Hallucinations Peripheral vasospasm (Raynaunds) Respiratory depression (Apomorphine

Amantadine (Symmetrel) antiviral drug

FOR dyskinesis produced Levodopa MoA:

Stimulates release & Reduces reuptake dopamine

Pharmacokinetics:

Well absorbed, long half-life, excreted unchanged by the kidney Ankle oedema, postural hypotension, nervousness, insomnia, hallucinations (high dose)

Adverse effects:

Other Disease Modifying Drugs

Selective monoamine oxidase B inhibitors (selegiline):

MoA: prolongs the effects of levodopa as MAO-B degrades dopamine Pharmacokinetics: completely absorption, short half-life Adverse effects: N, V, Dia, Constipation; dry mouth, sore throat; transient dizziness; insomnia, confusion and hallucinations Early stage prescribed on it is own to delay need for levodopa and there is good evidence for its slowing down of PD progression

COMT

(entacapone, Trade name Comtess)

MoA: inhibits breakdown levodopa Pharmacokinetics:, first-pass metabolism, short half-life Adverse effects: dyskinesias, hallucinations, abdominal pain New combination Levodopa/carbidopa/entacapone (Stalevo) as 1 tablet (50, 100, 150mg)

Antimuscarinic/Anticholinergic

Drugs:Trihexyphenidyl (Broflex, Artane, Agitane); Benztropine (Cogentin); Orphanadrine (Disipal); Procycline (Kemadrin, Arpicolin) MoA: blocking cholingeric Pharmacokinetics: fairly well absorbed, hepatic metabolism, long half-lifes : dry mouth and confusion

Antidepressants

Amitriptyline (Tryptizol), imipramine (Tofranil), Nortriptyline (Allegron), Iofepramine (Gamanil) MoA: block re-uptake of noradrenaline and serotonin => Sedative actions, Interfere levodopa!

Other Drugs to Avoid

Generic Name
Prochlorperazine Prephenazine Flupentixol
Chlorpromazine Pimozide Sulpiride

Brand Name
Stemetil Triptafen Fluanxol/Depixol
Largactil Orap Dolmatil

Prescribed for
N +V, Dizziness Depression Confusion, Hallucinations