This document discusses antiparkinsonian drugs used to treat Parkinson's disease. It defines Parkinsonism as a motor disorder caused by an imbalance of acetylcholine and dopamine in the basal ganglia. The main types of Parkinson's disease are described as idiopathic, vascular, inherited, and drug-induced. Antiparkinsonian drugs work by increasing dopamine levels through precursor drugs like levodopa, agonists, and inhibitors of enzymes that break down dopamine. Levodopa is discussed in detail, along with its mechanism of increasing dopamine in the brain. Adverse effects and drug interactions of levodopa are also summarized.

1. Antiparkinsonian drugs
Presented by
K.Lakshmi
Department of pharmacology
Assistant professor
SSPC

2. Who is he?

3. PARKINSON`S DISEASE (PD):-
History –
• Parkinson's disease was first formally
described in 1817 by a London physician
named James Parkinson.

4. DEFINITION
Parkinsonism is an extra pyramidal motor disorder,
symptoms includes- rigidity, tremors, with defective
gesture and posture. Parkinsonism is a result of
imbalance between acetylcholine and dopamine.
When there is remarkably decrease in dopamine level
or increase in acetylcholine level, Parkinsonism take
place. As cause is clear their treatment is also very
clear. Treatment goal is to restore the balance
between above said neurotransmitters either by
increasing dopamine by external source or by
decreasing the level of acetylcholine.

5. TYPES OF PD
Idiopathic Parkinson's disease:-
• Idiopathic Parkinson's disease - or Parkinson's
- is the most common type of parkinsonism.
Unlike some other forms which have specific
causes it is not known why idiopathic
Parkinson's occurs.
• The main symptoms of idiopatic Parkinson's
are tremor, rigidity and slowness of
movement.

6. Vascular Parkinsonism:-
• Vascular parkinsonism is one of the atypical
forms of parkinsonism.
• The most likely causes of vascular parkinsonism
are hypertension and diabetes. A stroke
(cerebrovascular accident), cardiac disease or
carotid artery pathology (another form of stroke)
may also be involved.
• Symptoms of vascular parkinsonism may include
difficulty speaking, making facial expressions or
swallowing.
• Other signs can include problems with memory
or confused thought, cognitive problems and
incontinence.

7. Inherited Parkinson's:-
• It is thought that although it is not directly
inherited, some people may have genes that
increase the possibility of developing
Parkinson's.
• People who have genes that are prone to
Parkinson's may be more likely to develop the
condition when combined with other factors,
such as environmental toxins or viruses.
• At present, it is estimated that up to 5% of
people with Parkinson's may have a genetic
cause.

8. Drug Induced Parkinsonism:-
•Antipsychotics: Chlorpromazine, Fluphenazine
and Haloperidol
•Antihypertensive like Reserpine
•Antiemetics: Metoclopramide and
Prochlorperazine
•Most people will recover within months, and
often within hours or days, of stopping the
drug that caused the dopamine block.
•Not associated with loss of nerve cells in the
substantia nigra

10. Imbalance primarily between the
excitatory neurotransmitter Acetylcholine
and inhibitory neurotransmitter Dopamine
in the Basal Ganglia

12. Antiparkinsonian Drugs
Definition:- Antiparkinsonian agents are drugs
which are used to treat Parkinson's disease
(PA).
Classification:-
I. Drug affecting brain dopaminergic system:-
1.Dopamine Precursor -Levodopa (L-dopa)
2.Peripheral decarboxylase inhibitor -
Carbidopa, Benserazide

13. 3.Dopaminergic Agonist -Bromocriptine,
Ropinirole, Pramipexole
4.MAO- B Inhibitor –Selegiline,Rasagiline
5.COMT Inhibitor -Entacapone, Tolcapone
6. Dopamine Facilitators (glutamate / NMDA
receptor agonist)- Amantadine
II. Drug affecting brain cholinergic system:-
1. Central Anticholinergics -Trihexyphenidyl,
Procyclidine, Biperiden, Benztropine, Benhexol
2. Antihistaminic -
Orphenadrine,Promethazine,Diphenhydramine

15. Mechanism of action

16. Pharmacology Levodopa
• Single most effective agent in PD
• 95% is decarboxylated to dopamine in gut and
liver
• 1 - 2% crosses BBB, taken up by neurones and
DA is formed

17. Mechanism
1. Because dopamine does not cross the blood-brain
barrier levodopa, the precursor of dopamine, is given
instead.
2. Levodopa is formed L-tyrosine and is an
intermediate in the synthesis of catecholamines.
3. Levodopa itself has minimal pharmacologic
activity, in contrast to its decarboxylated product,
dopamine.
4. Levodopa is rapidly decarboxylated in the
gastrointestinal tract. Prior to the advent of
decarboxylase inhibitors (carbidopa), large oral
doses of levodopa were required; thus, toxicity from
dopamine was a limiting factor.

18. Pharmacological actions
CNS:
Effective in Eliminating Most of the Symptoms
of Parkinson Disease
Bradykinesia and Rigidity Respond Quickly
Reduction in Tremor Effect with Continued
therapy
 Handwritting , speech, facial expression and
interest in life improves gradually
L -Dopa less Effective in Eliminating Postural
Instability

19. CVS:
• Cardiac Stimulation Due to Beta adrenergic effect on
Heart
• Though stimulates peripheral adrenergic receptor – no rise
in BP
• Orthostatic Hypotension - some individuals – central DA
and NA action
• In elderly cardiovascular problems -tachycardia, cardiac
arrhythmias and hypertension
CTZ:
DA receptors cause stimulation – nausea and vomiting
ENDOCRINE:
Decrease in Prolactin level and increase in GH
release

20. Behavioural Effects:
• Partially Changes Mood by elevating
mood, and increases Patient sense of well being
• General alerting response
• Disproportionate increase in sexual activity
• No improvement in dementia

21. Pharmacokinetics
• Absorbed rapidly from small intestine – aromatic
amino acid transport system
• High First Pass Effect – large doses
• Peak plasma conc. 1-2 hrs and half life - 1 to 3 Hrs
• Metabolized in liver and peripherally - secreted in
urine
• In CNS – Decarboxylated and DA is formed –
therapeutic effectiveness
• metabolized by MAO and COMT

22. Adverse effect:
Principal adverse effects include:
(1) Anorexia, nausea, and vomiting upon initial
administration, which often limit the initial dosage.
(2) Cardiovascular effects, including tachycardia,
arrhythmias, and orthostatic hypotension.
(3) Mental disturbances, including vivid dreams,
delusions, and hallucination.
(4) Hyperkinesia
(5) On-off phenomena-Sudden discontinuation can
result in fever, rigidity, and confusion. The drug
should be withdrawn gradually over 4 days.

23. Drug Interactions
• Pyridoxine – abolishes therapeutic effect of levodopa
• Antipsychotic Drugs – Phenothiazines, butyrophenones block the
action of levodopa by blocking DA receptors.
• Antidopeminergic – domperidone abolishes nausea and vomiting
• Reserpine – blocks levodopa action by blocking vesicular uptake
• Anticholinergics – synergistic action but delayed gastric emptying
–
reduced effect of levodopa
• Nonspecific MAO Inhibitors – Prevents degradation of peripherally
synthesized DA – hypertensive crisis by the tyramine-cheese effect
(tyramine is found in cheese, coffee, beer, pickles and chocolate),

24. CARBIDOPA:-
Carbidopa is an inhibitor of dopa
decarboxylase. Because it is unable to
penetrate the blood-brain barrier, it acts to
reduce the peripheral conversion of
levodopa to dopamine.
As a result, when carbidopa and levodopa
are given concomitantly:
a. It can decrease the dosage of
levodopa.
b. It can reduce toxic side effects of
levodopa.

29. Best advice from myself in 2
lines.....
silence is the best answer for
all questions........
Smiling is the best reaction in
every situation......