Pharmacological management of

Parkinson's disease
Dr Mozna Talpur
Parkinson disease or paralysis agitans
 Basic patho-physiology of Parkinson disease is loss of
dopaminergic neurons in substantia nigra which normally
inhibit output of GABAergic cells in corpus striatum.
Clinical Features
 Rigidity
 Bradykinesia
 Tremors
 Postural instability
Drugs used in Parkinsonism
1. Dopaminergic Agonist
a) Levodopa 1. COMT inhibitors
b) Bromocriptine a) Tolcapone
c) Apomorphine b) Entacapone
2. Dopa decarboxylase 2. Acetylcholine blockers
inhibitor a) Benztropine
a) Carbidopa b) Biperodine
3. MAOIs 3. Miscelleneous
a) Selagiline a) Amantidine
b) Rasagiline
Levodopa
 MOA:
 Dopamine can not cross BBB, but levodopa can cross BBB.
 Levodopa, if given alone, it is converted to dopamine by action
of enzyme dopadecarboxylase, so levodopa is given along with
carbidopa to prevent peripheral conversion.
 Clinical uses

 Maintainence therapy of Pakinsons disease.

Adverse reaction:
 Anorexia  Somnolence
 Nausea  Delusions
 Vomiting  Nightmares
 Tachycardia  Agitation
 Ventricular extra systole  Hallucinations
 Cardiac Arrhythmias  Euphoria
 Atrial fibrillation  Mydriasis
 Depression  Brown discoloration of
 Anxiety urine saliva
Fluctuation in response
 On-off phenomenon:
 It occurs after years of treatment.
 There is fluctuation in response related to timing of levodopa
intake and are referred as wearing off reaction or end dose
akinesia
 Management:
 Inj: Apomorphine s/c.
Drug Holiday
 Discontinuation of drug for 3-21 days may temporarily
improve responsiveness to levodopa and alleviate some of
its adverse reaction
 Drug interaction:
 Vit. B6 increases metabolism of levodopa
 Levodpa should not be given to patient taking MAOIs or with
in two weeks of their discontinuation because it may lead to
hypertensive crisis.
Contra-Indication
 Psychotic patient.
 Angle closure glaucoma
 Cardiac patient
Apomorphine
 Clinical use:
 Patient with on-off phenomenon for treatment of off period.
 Side effects:
 Nausea
 Drowsiness
 Chest pain
 Sweating
 Bruising at injection site
Monoamino-oxidase inhibitors
 MAOA metabolizes NE, 5HT and tyramine.
 MAOB metabolizes Dopamine.
 MOA:
 Inhibits metabolism of dopamine and prolong the anti
parkinson effect of levodopa.
 It may also reduce chances of on-off phenomenon.
 S/E:
 Insomnia. Same as dopamine.
 C/I:
 TCA because it may lead to serotonin syndrome.
Catechol-o-methyl transferase inhibitors
 MOA:
 Inhibition of dopa decarboxylase inhibitors leads to activation
of other enzyme (COMT) which increases 3-o-methyldopa.
This compound is associated with poor therapeutic response
because it competes with levodopa for active site.
 S/E:
 Dyskinesia, nausea confusion.
 Diarrhea, abdominal pain, orthostatic hypotension, sleep
disturbances and orange colour urine.
 Tolcapone increases liver enzymes.
Amantadine
 It is anti viral drug with anti parkinson effect.
 MOA:
 Increases synthesis, release and decrease re-uptake of
dopamine.
 S/E:
 Restlessness, Depression, Irritability, insomnia, excitement,
confusion, agitation, hallucination.