antiparkinsonian drugs,

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2.  It is a chronic, progressive, motor disorder
characterized by
 Tremor, resting
 Rigidity, cogwheel
 Akinesia, bradykinesia
 Postural Instability
ETIOLOGY-genetic, environmental toxins, and
endogenous toxins, from cellular oxidative reactions.
Two major pathogenetic hypotheses:
Misfolding of proteins
Mitochondrial dysfunction and oxidative stress
Pope John Paul
II

3.  Behavioral – depression, anxiety, decreased
motivation, personality changes,
 Sensory – non-specific pains,, restless legs and other
sleep problems
 Autonomic – constipation, bladder dysfunction,
impotence, low blood pressure
Muhammad
Ali

4. DRUGS THAT INCREASE DOPAMINE LEVELS
DA PRECURSOR-LEVODOPA
DRUGS THAT RELEASE DOPAMINE-AMANTIDINE
DOPAMINERGIC AGONISTS-BROMOCRIPTINE
PERGOLIDE, LISURIDE, ROPINIROLE
INHIBIT DOPAMINE METABOLISM-
MAO INHIBITORS-SELEGILINE, RASGILINE
COMT INHIBITORS-TOLCAPONE, ENTACAPONE

5. DRUGS INFLUENCING CHOLINERGIC SYSTEM
 CENTRAL ANTICHLINERGICS-BENZTROPINE,
BENZHEXOL, BIPERIDINE
 ANTIHISTAMINES-DIPHENHYDRAMINE,
ORPHENADRINE, PROMETHAZINE

6. Bradykinesia, rigidity, mild tremor, rabbit syndrome
Caused by exposure to a dopamine-receptor
blocking agent within 6 months of the onset of
symptoms
Offending drugs include: antipsychotics, anti-emetics,
metoclopramide
1. Mild cases can frequently remit after cessation of the
offending drug
2. Usually unresponsive to dopaminergic therapy
3. Elderly patients are most susceptible
4. Treatment may include: tetrabenazine, reserpine,
vitamin E, benzodiazepines

8.  still the best, especially short term
 long term use – motor fluctuations, dyskinesias
 inversely proportional to age
 but – nearly all patients eventually require it
 extends half-life of levodopa, early use
 for early symptomatic treatment and for rapid
response, i.e. to aid patient to continue working –
especially for rigidity & bradykinesia

9.  Helps bradykinesia and rigidity (not really tremor)
 Small dose increments every few days
 6-18 months to see improvement
ADR- Nausea/flushing/sweating/neuropathy
DEMERITS-On-off effect
End of dose deterioration

10.  Ropinorole, Pramipexole, Pergolide
 Bromocriptine/Cabergoline now avoided due to
cardiac valvulopathy and pleural, pericardial and
retroperitoneal fibrosis
 Dose -incremental increases
 Similar S/E profile, less motor complications but less
improvement

11. DEMERITS-impulse control disorders and excessive
daytime somnolence
 Hypotension particularly in first few days of
treatment
 Good evidence in advanced PD to improve off time-
transdermal Rotigotine
 Amantadine-weak dopamine agonist
 Increasing Dopamine Agonists often worsens
hallucinations

12.  Antiviral properties.
 Weak DA, NMDA-receptor antagonist properties-
interferes with excessive glutamate, Glutamate
antagonist.
 Only for moderate to severe dyskinesia.
 100 mg. BD or TDS
 for dyskinesias
 -SE-livedo reticularis, ankle edema, hallucinations

13.  Similar to levodopa
 Nausea.
 Vomiting.
 Postural hypotension.
 Confusion.
 Hallucinations.
 Somnolence.

14. Delays or reduces breakdown of dopamine by MAO-B.
Used as monotherapy or in conjunction with L-DOPA, it
can reduce the dosage of L-DOPA by 15%.
MAO-B is an enzyme that metabolizes dopamine.
From the breakdown of dopamine, hydrogen peroxide is
produced, which the oxidative stress can damage
dopaminergic neurons in the substantia nigra. (Possibly
neuroprotective)
Side effects of L-DOPA may be enhanced by selegeline.
 Nausea and dizziness.
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15.  Inactivates and degrades neurotransmitters,
such as dopamine.
 Mainly used in combination with L-DOPA, it
increases the half-life of L-DOPA.
 Delays “wearing-off” effect of L-DOPA and
other motor complications such as dyskinesia
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16.  COMT catalyzes methylation of L-DOPA.
 Addition of COMT inhibitor along with L-DOPA
and carbidopa prolongs the half-life of L-DOPA
and increases the amount in the CNS.
This increases “on” time for L-DOPA.
 Diarrhea and sleep disturbances
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17.  Before commerciality of levodopa, surgical
treatment were preferred.
 Early surgeries were successful with tremors, but
failed to relieve other symptoms.
 “Means of last resort” due to high risk of potential
complications.
 Recent advances in neurosurgical procedures allow
for better treatment.
 Deep Brain Stimulation-Brain pacemaker, sends
electrical impulses to brain to stimulate the
subthalamic nucleus.
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18.  MAO-B inhibitors
 Buccal selegiline or rasagiline can help motor
complications (less commonly used)
 Severe PD-can admit for subcutaneous
Apomorphine infusion
 New treatments-dopamine pump if others fail

19. - Benzatropine, Procyclidine, Orphenadrine
- Limited use.
- Cognitive impairment in elderly.
- Useful in drug induced Parkinsonism.
- can be used for excessive salivation.

20.  Orphenadrine-helps drooling
 Often drooling is more unpleasant for family & they
are delighted if you can improve this
 Procyclidine-Best in drug-induced Parkinsonism s/e
control
 SE-confusion, hallucinations, dry mouth, blurred
vision, constipation, nausea, u. retention, glaucoma