Dr.Rathnakar U.P.

BPT 20 NOV 2013

• 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

[Poverty of movements, tremors and rigidity]

Clinical features of PD
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



DA Ach

DA Ach


Normal DA=Ach

PD Deficiency of DA Relative excess of Ach

Treatment PD Dopaminergics Anticholinergics

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


Carbidopa Benserazide

Entacapone Tolcapone



1 Dopamine DDC Levodopa COMT 3-MDOPA

3 Selegiline Rasagiline Levodopa Tolcapone 3



Dopamine COMT 6

3MT 5
• • • • Anticholinergics Trihexyphenidyl Procyclidine Biperiden Antihistaminics


DA agonists

D1 & D2 Receptors

DA facilitator Amantadine

Drugs for PD
I.Drugs affecting brain dopaminergic system II.Drugs affecting brain cholinergic system

1. DA precursor- Levodopa 2. DDC inhibitors-Carbidopa 3. DA agonistsBromocriptine 4. MAO-B inhibitorsSelegiline 5. COMT inhibitorsEntacapone 6. DA facilitator-Amantadine

1. Central anticholinergics Trihexyphenydyl, procyclidine, biperiden 2. Antihistaminics Orphenadrine, promethazine


Levodopa Pharmacological actions
• CNS 1. Normal persons-no effect 2. PD: Excellent clinical improvement initiallyrigidity, hypokinesia, Tremors other nonmotor symptoms later 3. Psychosis 4. Sexual activity↑ • CVS 1. Tachycardia 2. Postural hypotension[central action] 3. Tolerance develops • Endocrine Prolactin↑

Levodopa ADEs
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-Anxietydepression-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.

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