Parkinsonism

Dr.Rathnakar U.P.MD.DIH.PGDHM

BPT20 NOV 2013

Contents

• Examples of antiparkinsonian drugs• Adverse effects of levodopa• Basis for combining levodopa with

carbidopa• Drugs used in drug-induced

parkinsonism and their mechanism of action

PD[Poverty of movements, tremors and rigidity]

Clinical features ofPD

Parkinson's disease (PD) is the second commonest neurodegenerative disease, exceeded only by Alzheimer's disease (AD). 5 million persons in the world suffer from this disorder.

Pathophysiology of PD

• "Dopaminergic" pathology Degeneration of dopaminergic neurons in SN [Deficiency of DA]

• “Non-dopaminergic" pathology Over activity cholinergic neurons,

DA and Ach in PD

AchAch Ach

DADA DA

NormalDA=Ach

PDDeficiency of DA

Relative excess of Ach

Treatment PDDopaminergics

Anticholinergics

DAAntichlonergics

Sites of action of drugs used to treat Parkinson's disease

Levodopa 3-MDOPADopamineDDC COMT

EntacaponeTolcapone

CarbidopaBenserazide

BBBBBB

Levodopa

Dopamine 3MTDOPACCOMTMAOB

SelegilineRasagiline

Tolcapone

D1 & D2 Receptors

DA agonists

1

2 2

33

4

Anticholinergics• Trihexyphenidyl• Procyclidine• Biperiden• Antihistaminics

5

0Stupid

6

DA facilitatorAmantadine

Drugs for PDI.Drugs affecting brain dopaminergic

system

1. DA precursor- Levodopa

2. DDC inhibitors-Carbidopa

3. DA agonists-Bromocriptine

4. MAO-B inhibitors-Selegiline

5. COMT inhibitors-Entacapone

6. DA facilitator-Amantadine

II.Drugs affecting brain cholinergic system

1. Central anticholinergics

Trihexyphenydyl, procyclidine, biperiden

2. Antihistaminics

Orphenadrine, promethazine

Levodopa

LevodopaPharmacological actions

• CNS

1. Normal persons-no effect

2. PD: Excellent clinical improvement initially- rigidity, hypokinesia, Tremors other non-motor symptoms later

3. Psychosis

4. Sexual activity↑

• CVS

1. Tachycardia

2. Postural hypotension[central action]

3. Tolerance develops• Endocrine

Prolactin↑

LevodopaADEs

At initiation of therapy• Nausea & vomiting• Postural hypotension• Cardiac arrhythmias• Exacerbation of angina• Alteration of taste

Prolonged therapy• Abnormal movements

[dyskinesia]-chorea, grimacing. Worsen with time• Dose limiting• Behavioral-Anxiety-

depression-psychosis• End of dose effect• On-off phenomenon[worsening and improvement in a few minutes-progressive degeneration]

Centrally acting anticholinergics

• Restore Ach/ DA balance in striatum

• Tremor is benefitted more than rigidity

• Less effective than L.dopa

• Cheap, less side effects• Atropine like side

effects

• Trihexyphenidil• Procyclidine• Biperiden• Orphenadrine• Promethazine

Drug induced Parkinsonism[Extrapyramidal symptoms]

Drug induced extrapyramidal reaction

• Antipsychotics - Phenothiazines• Antiemetic - Metoclopramide• Tt of acute reactions - Promethazine

25 mg.i.v

• Other drugs-Anticholinergics & antihistaminics with antiucholinergic activity

Physiotherapy and Parkinson’s Disease

• The main areas in which physiotherapists help people with Parkinson's Disease are:

• posture,• range of movement,• walking and turning,• balance and transfers.http://www.parkinsons.ie/aboutparkinsons_treatments_physio2