ANTI

PARKINSONIAN
DRUGS
Presented by : UMAIR AHMED ,
RCPER, MALEGAON
History of Parkinson´s disease (PD)
 First described ---- 1817 ---James Parkinson,
 “An Essay on the Shaking Palsy.”
• Charcot ----described the syndrome later
Epidemiology of PD
 most common movement disorder over
the age of 65 years

 affecting 1-2 %

 The second most common

neurodegenerative disorder after
Alzheimer´s disease (AD).
Tremor
Rigidity
Akinesia
Postural prob
 Causes
 Idiopathic Parkinson’s Disease-Paralysis
agitans
 Drugs (Dopamine Receptor Antagonists)
Antipsychotics, Metoclopramide
 Neurotoxins-MPTP-oxidative stress
Rotenone, Domoic acid
 Genetic-mutation of parkin and α synuclein
 Causes……………
 Stroke

 Viralinfection
 Trauma

 Wilson’s disease

 Space occupying lesion

 Pathophysiology
Pathological hall mark of PD is loss of
dopaminergic neurones of substantia nigra
pars compacta

LEWY
Normal
Parkinson’s disease
 Direct Pathway- Excitatory- D1 Receptors
 Indirect Pathway- Inhibitory – D2
Receptors
 Health – Direct pathway predominates
 PD - Indirect pathway predominates
CHOLINERGIC OVER ACTIVITY
 Drugs affecting brain dopaminergic
system
1- Dopamine precursor – Levodopa
2-Peripheral Decarboxylase Inhibitors
 Carbidopa, Benserazide
3- Dopaminergic Agonists-
 Bromocriptine, Pergolide
 Ropinirole,Pramipexole
4- MAO-B inhibitors- Selegiline,Rasagiline
5- COMT inhibitors – Entacapone , Tolcapone
6 – Dopamine Facilitator - Amantadine
Bromocriptine
Pergolide Levodopa
Pramipexole
Ropinirole

Amantadine Selegiline
Rasagiline
Levodopa
Drugs affecting brain cholinergic system

1 – Central anticholinergic
Trihexiphenidyl,Benztropine,Biperiden
Procyclidine
2 – Antihistamines
Orphenadrine , Promethazine
 Levodopa
 Universal antiparkinsonian drug
 Metabolic precursor of Dopamine
 Therapeutic effect ----decarboxylation in brain
 95% of oral dose is decarboxylated in periphery
 only 1 -2 % crosses BBB
 Always given along with peripheral decarboxylase
inhibitor
 Half life – 1-3 hrs
 Actions of Levodopa
CNS
Hypokinesia and rigidity resolve first
CVS
Tachycardia , postural hypotension
CTZ
Nausea ,vomiting – tolerance later
ENDOCRINE
Inhibit Prolactin
 Kinetics
 Absorbed from small bowel –
amino acid transporter
 Meal delays absorption
 1 hr before and 1hr after food
 High first pass metabolism in liver, git
 Side effects
At the initiation of therapy
1 – Nausea and vomiting
2 – Postural hypotension
3 –Cardiac arrhythmias
4 – Exacerbation of angina
5 – Alteration of taste sensation
 After prolonged therapy
1 – Abnormal movements
2 – Behavioral effects
3 – Fluctuation in response
OFF/ON phenomenon
Wearing of reactions – end of dose
 Interactions
1 – pyridoxine
2 – Phenothiazines , Butorphenones
X Metoclopramide
 Domperidone
3 – MAO inhibitors
4 -- Atropine
 Peripheral decarboxylase
inhibitors
Carbidopa , Benserazide
 Do not cross BBB
 Half life of L-Dopa increased
 Systemic side effects less
 Pyridoxine reversal does not occur
 ON/OFF phenomenon is minimized
 Degree of improvement higher
 Smooth control of symptoms
 Less diurnal fluctuations
LEVODOPA + CARBIDPOA
15% X
10%
 Dopamine receptor agonists
 ERGOT
 Bromocriptine
 Pergolide
 NON ERGOT
 Ropinirole
 Pramipexole
 Dopamine receptor agonists
 No enzymatic conversion needed
 Don’t require functional integrity of neurons
 Longer duration of action
 Less dyskinesia
 Less ON/OFF
 More selective
 BROMOCRIPTINE
 Synthetic ergot derivative
 D2 agonist
 Levodopa like action
 ↓GH and↓Prolactin
 Nausea &Vomiting-CTZ
 Hypotension –α blockade
 PK------1st pass metabolism
-----------t ½ -3-6 hours
 USES
 Parkinsonism
 Hyperprolactinemia
 Gynecomastia, impotence & sterility in men
 Acromegaly
 Suppress lactation
 Hepatic coma
 Side effects
 Early
 Nausea, Postural
hypotension,Vomiting,Constipation,nasal
block
 Late
 Hallucination, psychosis,pulmonary
infiltrates, retroperitoneal fibrosis,digital
vasospasm,erythromelalgia
 PERGOLIDE
 D1 and D2 agonist
 Increase ON time
 Less dose of L- dopa
 Withdrawn--- Valvular heart disease
 PRAMIPEXOLE
 D3 agonist
 Antioxidant property
 Early and advanced disease
 Less GI side effects
 Episodes of day time sleep-sleep attacks
 ROPINIROLE
 D2 agonist
 Metabolised in liver by CYP1A2
 Used in Restless leg syndrome
 Day time sleep
MAO I

MAO

MAO
 MAO inhibitors
Selegiline
 Irreversible MAO-B inhibitor
 Minimal effect when used as
monotherapy
 Increases ON time
 Reduce wearing off reaction
 ANTI OXIDATIVE EFFECT
 MAO Inhibitors
 Insomnia when taken later in the day
 5mg with break fast and 5mg with lunch
 S/E – Confusion , insomnia, hallucination
 Serotonin syndrome
 RASAGILINE
 COMT INHIBITORS
 Tolcapone ,Entacapone
 Inhibit levodopa metabolism
 ↑BA of levodopa
 Extends the t ½ of levodopa
 No role as monotherapy
 Indicated for patients with PD who have end-of-
dose wearing off
 S/E Dyskinesia , nausea, confusion
diarrhoea , abdominal pain,
orange coloured urine
Tolcapone------hepatotoxicity
Amantadine
 Dopamine facilitator
AMANTADINE
 Anti viral agent - Influenza A
 Influence pre synaptic synthesis,Release or
Reuptake of dopamine
 Anticholinergic activity
 Modulate NMDA glutamate receptor
 Amantadine used as initial therapy in mild
PD
 S/E - Livedo reticularis , ankle edema
Toxic psychosis , convulsion
Heart failure ,postural hypotension
 Contraindicated in seizure , CHF
 Central anticholinergics
Only drugs effective in DRUG INDUCED
PARKINSINISM
Trihexyphenidyl, Benztropine
 Tremor is relieved first
 Efficacy lower than L-dopa
 Cheaper
 Contraindicated in narrow angle glaucoma,
prostatic hyperplasia
 ANTIHISTAMINE
Better tolerated by older patients
S/E Dryness of mouth ,suppurative parotitis
Mohammed Ali
Michael J. Fox
Johnny Cash Thank U
Billy Graham
Pierre Trudeau
Pope John Paul 2