Information about psychological Disease & Drugs. Learn Parkinson disease with easy & simple way.

1. ANTI-PARKINSONIN DRUGS.
BYRUCHASANTOSHTIWARI,
FINALYEARB.PHARMSTUDENT,
FROMNASHIK.

2. DEFINING PARKINSON'S DISEASE.
• A disorder of the central nervous system that affects movement,often including
tremor.
• Nerve cell damage in the brain causes dopamine level to drop, leading to the
symptoms of Parkinson.
• Parkinson's disease was first medically described as a neurological
syndrome by James Parkinson in 1817.

3. PARKINSON‘S DISEASE SIGN & SYMPTOMS

4. DIAGNOSIS & TEST OF PARKINSON‘S DISEASE.
• It has been estimated that, especially in it’s early stages, nearly 40% people with
Parkinson’s disease may not be diagnosed & as many as 25% are misdiagnosed.
1. PET SCAN :- A Positron Emission Topography (PET) scan is the test used to
give you & your doctor‘s known more information about how the cells in your
body are functioning.
2. CT SCAN :- CT or Computer tomography uses X- ray & computers to
produce image of inside the body , including the brain . This test is used to
look for signs of diseases like Parkinson.

5. 3. MRI :- A Magnetic Reasonance Imaging is the test that produces very clear
image of human body than X- ray.
4. SPECT SCAN :- Single- Photon Emission Computerized Tomography sacn
..This is also called a Dopamine Transporter (DAT) scan.

6. SYNTHESIS & METABOLISM OF DOPAMINE
SYNTHESIS
• DA is synthesized in restricted set of
cell types, mainly neurones & cells in
the medulla of adrenal glands.

7. METABOLISM
• HVA :- Homovanilic acid.
• DOPAC :- 3,4 Dihydroxy-phenyl Acetic
Acid.( It is neurotransmitter of DA)
• 3-MT :- 3-Methoxy Tyramine. It is
human trace amine that occurs as a
metabolite of the neurotransmitter
Dopamine.

8. STORAGE, RELEASE & REUPTAKEOF DOPAMINE.
• Dopamine is stored in vesicles until it is ejected into the synaptic cleft .
• DA is one of the chemical signal that pass information from one neurones to the
next in the tiny space Between them
• The brain release it, when we eat Food that we crave OR while we have sex,
contribution to feelings of pleasure.

9. TREATMENT USED TO PD.
• Although Parkinson's disease can't be cured, treatments are available
to help reduce symptoms and maintain quality of life. These include
supportive therapies such as physiotherapy, occupational therapy and
psychological counselling that help you cope with everyday life, or
medication to control your symptoms. Surgical procedures such as deep
brain stimulation may be used under the direction of doctors.

10. • Antiparkinsonian drugs are medicines used to treat the symptoms of
Parkinson's disease. The majority of the registered antiparkinsonian
drugs in Hong Kong are available in oral dosage forms e.g. tablets,
capsules; while a few of them are presented in injectable forms and
transdermal patches.

11. CLASSIFICATION OF ANTI-PARKINSONIN DRUGS
• Antiparkinsonian drugs consist largely of the use of dopaminergics or
antimuscarinics in an attempt to restore the normal balance between
dopaminergic and cholinergic activity. Drugs with different actions may
be necessary to achieve optimum control of symptoms. The medications
may include:

12. (A) DRUGS ACTING ON DOPAMERGIC SYSTEM.
1. Dopamine precursor :- Levodopa (L- DOPA)
2. Peripheral DOPA decarboxylase inhibitor :- Carbidopa
3. COMT inhibitor :- Tolcanpone, Entacanpone
4. Selective MAO- inhibitor :- Selegilline, Rasagilline, Moclebemide.
5. Dopaminergic agonist (Ergot alkaloid) :- Bromocriptine.
6. Dopamine facilitators :- Amantadine

13. (B) DRUGS AFFECTING CHOLINERGIC SYSTEM.
1. Anti-histamic :- Promethazine, Ophenadrine.
2. Central Anti-cholinergic :- Trihexyphenidyl, Procyclidine, Biperiden.
Let’s see individual drugs…

14. (A) DRUGS ACTING ON DOPAMERGIC SYSTEM.
DOPAMINE PRECURSOR
LEVODOPA
• This drug is the most effective medication to control the symptoms of
Parkinson’s disease. It is absorbed by the nerve cells in your brain and
is converted to dopamine. Levodopa is usually combined with a
peripheral dopa-decarboxylase inhibitor such as benserazide or
carbidopa. Dopa-decarboxylase inhibitors prevent the breakdown of
levodopa in the gut, which allows effective concentrations of dopamine
to be achieved in the brain with lower doses of levodopa, and also
reduces side effects such as nausea and vomiting.

15. MACHANISM OF ACTION OF LEVODOPA
Levodopa is converted to dopamine via the action of a naturally occurring
enzyme called DOPA decarboxylase. This occurs both in the peripheral
circulation and in the central nervous system after levodopa has crossed
the blood brain barrier.

16. PHARMACOLOGICAL ACTION OF LEVODOPA
1. CNS :-
• L-DOPA hardly produces any effects in normal individual OR in patients with
other neurological disease.
• Marked symptomatic improvement occurred in Parkinson patients.
• Hypokinesia & rigidity resolve first, later tremor as well.

17. 2. CVS :-
• The peripherally formed DA can Causes tachycardia by acting on beta-
adrenergic receptors.
• Though DA can stimulate vascular adrenergic receptors as well, rise in BP is not
seen.
• DA & NA formed in brain decreases sympathetic action.

18. 3. ENDOCRINE :-
• DA act on pituitary mammotropes to inhibits prolactin release & on
somatotropes to increases GH release.
• Though prolactin levels in blood fall during Levodopa therapy, increases GH
level are not noted in Parkinson patients.

19. PHARMACOKINETICS OF LEVODOPA
• Rapidly absorbed from small intestine by utilising active transport.
• L-DOPA undergo first pass metabolism in G.I. mucosa & liver.
• The plasma half life :- 1-2 hrs.
• A/E :- Nausea, Vomiting, Lightheadedness, Drowsiness, Involuntary
movements.
• Dose :- 0.4-0.8mg along with 75-100mg Carbidopa OR 100-200mg
Benserazide given in 3-4 divided doses.

20. DRUG INTERACTIONS OF LEVODOPA
1. L-DOPA + Phenothiazine = Reverse therapeutic effects of Levodopa by
blocking DA receptor.
2. L-DOPA + Reserpine = Abolished L-DOPA action by preventing entry of DA
into synaptic vesicles.
3. L-DOPA + Non-Selective MAO inhibitor = Hypertensive crisis can occurred.
4. L-DOPA + Anti-Hypertensive = Postural hypotension occurred.

21. PERIPHERAL DOPA DECARBOXYLASE INHIBITOR
CARBIDOPA / BENSERAZIDE
• Do not penetrate BBB & do not inhibit conversion of Levodopa to DA in the brain.
• Along with L-DOPA, make more of it available to cross BBB
• BENEFIT OF COMBINATION
• The plasma half life L-DOPA is prolong.
• Dose reduce to ¼ th.
• Therepeutic dose of L-DOPA attained quickly.
• Cardiac complications are minimised.

22. DOPAMINERGIC AGONIST
BROMOCRIPTINE
• It is an Ergot derivative which act as potent agonist on D2, but as partial agonist OR
antagonist on D-1 receptor.
• Improvement in Parkinsonism symptoms occurs within 1½ hrs of an oral dose & last for 6-10
hrs .
• It may be administered both orally and IV – and has a half-life of around 12 hours.
• Bromocriptine is primarily excreted in the bile.
• Reduce A/E :- Nausea, Vomiting, Hallucination, Hypotension.
• Produce fall in BP with the first dose.
• Low doses (1.25mg once at night) & gradually increasing upto 5-10mg trice daily.

23. MAO-B INHIBITOR
SELEGILINE(DEPRENYL)
• It is selective & irreversible MAO-B inhibitor.
• Selegilline alone has mild anti- Parkinson action.
• Administrated with L-DOPA, it prolong L-DOPA action.
• A/E :- Postural hypotension, confusion.
• Doses :- 5mg with breakfast & with lunch..
Elderly:- 5-10mg tab(selerin)

24. COMT INHIBITOR
ENTACAPONE & TOLCAPONE
• Two selective , potent & reversible COMT inhibitor i.e. Entacapone & Tolcapon have
been introduced as adjuvant to L-DOPA-Carbidopa for advanced PD.
• When peripheral decarboxylase of Levodopa is blocked by Carbidopa, it is mainly
metabolites by COMT to 3-O-methyldopa.
• Blockade of this Pathways by Entacapone/Tolcapone, prolong the half life of
Levodopa & allow a larger fraction of administrated dose to cross to brain.
• However, Entacapone acts only in the peripheral.( Because of short DOA ~2hrs)

25. • Tolcapone dose is 100-200mg BD or TDS.
• A/E of Levodopa occurred by adding COMT inhibitor, however this can be
minimised by adjustment of L-DOPA dose.
• A/E :- Diarrhoea, Yellow orange discoloration of urine, Hepatotoxicity (less in
Entacapone).
• (While tolcapone does cross the blood-brain barrier, entacapone does not.
COMT inhibitors do have short half-lives, around two hours, and the enzyme
COMT does break down levodopa both peripherally and in the CNS. Tolcapone
is well absorbed from the gut, whereas entacapone is moderately absorbed
from the gut.)

26. DOPAMINE FACILITATOR
AMANTADINE
• It is a weak dopamine agonist with some antimuscarinic activity.
• It has mild antiparkinsonian effects compared with levodopa.
• It may be used alone to provide short-term relief of symptoms of mild,
early-stage Parkinson's disease, and may also be given with levodopa
therapy during the later stages of the disease to control involuntary
movements induced by levodopa.
• A/E :- Gastro-intestinal disturbances, Anorexia, Dry month, Palpitation,
Lethargy, Dizzines, purple mottling of the skin, Ankle swellin,
Hallucinationn.

27. (B) DRUGS AFFECTING CHOLINERGIC SYSTEM.
CENTRAL ANTI-CHOLINERGIC
• These are drugs having a higher central ; peripheral Anti-cholinergic action ratio
than atropine, but p’cological profile is similar to it.
• All Anti-cholinergic produced 70-25% improvement in clinical features, lasting
4-8 hrs After a single dose.
• The overall efficiency is much lower than Levodopa.
• However, they are cheap & produced less side effects than L-DOPA.
• Anti-cholinergic are the only drugs effective in drug (Phenothiazine) induced PD.

28. 1. Trihexyphenidyl :- It is most commonly used drug. Start with lowest dose in 2-
3 divided portions per day & gradually increases till side effects are tolerated.
Dose :- 2-10mg/day.
2. Procyclidine :- 5-20 mg / day.
3. Biperiden :- 2-10 mg / day ; oral, IM, IV.
4. Orphenadrine :- 100-300 mg / day.
5. Promethazine :- 25-75 mg / day.

29. CHECK YOUR KNOWLEDGE
1. The predominant clinical effect from dopamine receptor agonists comes
from their activity on which receptor?
• A) D1. B) D2. C) D3. D) D4.
2. Rasagiline and selegiline are irreversible inhibitors of the MAO-B enzyme.
• A) True
• B) False

30. 3. Which of the following drug(s) are dopa decarboxylase inhibitors?
• A) Carbidopa
• B) Rotigotine
• C) Pergolide
• D) Benserazide

31. 4. Which of the following statements about COMT inhibitors is false?
• A) COMT inhibitors have short half-lives, around 2 hours.
• B) COMT breaks down levodopa both peripherally and in the CNS.
• C) COMT inhibitors cross the blood-brain barrier.
• D) Tolcapone is well absorbed from the gut

32. 5. Which of the following statements about bromocriptine is false?
• A) Potent agonist at D2 receptors.
• B) Administered both orally and IV.
• C) Primarily excreted in the bile.
• D) None of the above.

33. Thank you