Class antiparkinsonian drugs

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
PosturalInstability
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
Causedby exposure to a dopamine-receptor
blockingagent within 6 months of the onset of
symptoms
Offending drugsinclude: 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-offeffect
Endof dose deterioration

10. Ropinorole, Pramipexole, Pergolide
Bromocriptine/Cabergoline now avoided due to
cardiac valvulopathy and pleural, pericardial and
retroperitoneal fibrosis
Dose-incrementalincreases
SimilarS/Eprofile, less motor complications but less
improvement

11. DEMERITS-impulsecontrol 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 dopamineagonist
Increasing Dopamine Agonists often worsens
hallucinations

12. Antiviral properties.
WeakDA,NMDA-receptor antagonist properties-
interferes with excessiveglutamate,Glutamate
antagonist.
Onlyfor moderate to severe dyskinesia.
100mg. BD orTDS
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 effectsof 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 BrainStimulation-Brainpacemaker, sends
electrical impulses to brain to stimulate the
subthalamic nucleus.
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18. MAO-Binhibitors
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-Bestin drug-induced Parkinsonism s/e
control
SE-confusion, hallucinations, dry mouth, blurred
vision, constipation, nausea, u. retention, glaucoma