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Parkinsonism

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

BPT 20 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 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

Antichlonergics

Ach

DA Ach

DA Ach

DA

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

0
Stupid

1 Dopamine DDC Levodopa COMT 3-MDOPA

BBB
3 Selegiline Rasagiline Levodopa Tolcapone 3

BBB

DOPAC
MAOB

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

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 Parkinsons 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