This document discusses neurodegenerative disorders like Parkinson's disease. It covers the etiology, signs and symptoms, stages of the disease, and drugs used to treat it. Parkinson's is primarily caused by the loss of dopamine-producing neurons in the brain. Common signs include tremors, rigidity, slow movement, and postural instability. Treatment focuses on replacing dopamine or stimulating dopamine receptors using drugs like levodopa, carbidopa, bromocriptine, amantadine, and selegiline.

1. NeurodegenerativeNeurodegenerative
DisordersDisorders

2. ETIOLOGYETIOLOGY
• PRIMARYPRIMARY
• Also called paralysis agitansAlso called paralysis agitans
• HypothesisHypothesis
• Absorption of highly potent neurotoxinsAbsorption of highly potent neurotoxins
• ManganeseManganese
• Carbon monoxideCarbon monoxide
• Exposure to free radicalsExposure to free radicals

3. SECONDARYSECONDARY
• PHENOTHIAZINESPHENOTHIAZINES
• BUTYROPHENONESBUTYROPHENONES
• RESERPINERESERPINE
• ENCEPHALITISENCEPHALITIS
• METABOLIC DISORDERSMETABOLIC DISORDERS

4. S/SXS/SX
• TREMOR AT RESTTREMOR AT REST
• LIMB RIGIDITYLIMB RIGIDITY
• AKINESIAAKINESIA
• BRADYKINESIABRADYKINESIA
• GAIT AND POSTURAL DIFFICULTYGAIT AND POSTURAL DIFFICULTY
• RHYTHMIC PILL ROLLING TREMORRHYTHMIC PILL ROLLING TREMOR

5. • Cogwheel rigidityCogwheel rigidity
• Masking of faceMasking of face
• Shuffling gaitShuffling gait
• MicrographiaMicrographia
• Bladder incontinenceBladder incontinence

6. Stages of Parkinson’s diseaseStages of Parkinson’s disease
0. No clinical signs evident0. No clinical signs evident
1. Unilateral involvement, including the major features of1. Unilateral involvement, including the major features of
tremor, rigidity, or bradykinesia; minimal functionaltremor, rigidity, or bradykinesia; minimal functional
impairmentimpairment
2. Bilateral involvement but no postural abnormalities2. Bilateral involvement but no postural abnormalities
3. Mild to moderate bilateral disease, mild postural3. Mild to moderate bilateral disease, mild postural
imbalance, but still ability to function independentlyimbalance, but still ability to function independently
4. Bilateral involvement with postural instability; patient4. Bilateral involvement with postural instability; patient
requires substantial assistancerequires substantial assistance
5. Severe disease; patient restricted to bed or wheelchair5. Severe disease; patient restricted to bed or wheelchair
unless aidedunless aided

7. Drugs Used in Parkinson'sDrugs Used in Parkinson's
DiseaseDisease
• Start slow – go slowStart slow – go slow
• act by counteracting deficiency of dopamine in basalact by counteracting deficiency of dopamine in basal
gangliaganglia
• by blocking muscarinic receptors.by blocking muscarinic receptors.
• LevodopaLevodopa (L-Dopa)sinemet 1:4(L-Dopa)sinemet 1:4
– dopamine precursor that passes BBBdopamine precursor that passes BBB
– given with an inhibitor of peripheral dopaminegiven with an inhibitor of peripheral dopamine
decarboxylase (e.g.decarboxylase (e.g. carbidopacarbidopa))
– High protein diet causes competition for the drugHigh protein diet causes competition for the drug
uptakeuptake
– effective in patients but loses efficacy after about 2effective in patients but loses efficacy after about 2
years.years.

8. Drugs Used in Parkinson'sDrugs Used in Parkinson's
DiseaseDisease
• Levodopa and Carbidopa (Sinemet)Levodopa and Carbidopa (Sinemet)
– First line of drug usedFirst line of drug used
– Adverse effectsAdverse effects
– Nausea, psychosis, anxietyNausea, psychosis, anxiety
– Chronic useChronic use  facial grimacing, jerkingfacial grimacing, jerking
– May speed progression of disease (latency ofMay speed progression of disease (latency of
disease)disease)
– On-Off effectOn-Off effect
– Down regulation dosage /drug holidayDown regulation dosage /drug holiday
– Antacids – increases absorptionAntacids – increases absorption
– MAOIS- Hypertensive crisisMAOIS- Hypertensive crisis
– Pyridoxine- co enzyme of carbidopa-decreasesPyridoxine- co enzyme of carbidopa-decreases
pharma effectpharma effect

9. SESE
• DECLINING EFFICACYDECLINING EFFICACY
• GITGIT
• INVOLUNTARY MOVEMENTSINVOLUNTARY MOVEMENTS
• TACHYCARDIATACHYCARDIA
• ARRHYTMIAARRHYTMIA
• POSTURAL HYPOTENSIONPOSTURAL HYPOTENSION
• CONFUSSION,DEPRESSIONCONFUSSION,DEPRESSION

10. Drugs Used in Parkinson'sDrugs Used in Parkinson's
DiseaseDisease
• AmantadineAmantadine
– Increase release of dopamine at nerve terminalsIncrease release of dopamine at nerve terminals
– Less efficient than SinemetLess efficient than Sinemet
– Restlessness, dry mouth, hallucinationsRestlessness, dry mouth, hallucinations
– More rapid reliefMore rapid relief
• BromocriptineBromocriptine
– agonists of postsynaptic dopamine receptorsagonists of postsynaptic dopamine receptors
– added in patients with inadequate response toadded in patients with inadequate response to
SinemetSinemet
– Inhibit prolactin secretion( used for prolactinomas)Inhibit prolactin secretion( used for prolactinomas)
– Pulmonary problems.avoid alcoholPulmonary problems.avoid alcohol

11. BromocriptineBromocriptine
• Ergot derived direct agonist of D2Ergot derived direct agonist of D2
receptorsreceptors
• SE: vasoconstriction, PUD, retroperitonialSE: vasoconstriction, PUD, retroperitonial
fibrosisfibrosis

12. • PERGOLIDE – ergot alkaloid agonist atPERGOLIDE – ergot alkaloid agonist at
D2D2
• PRAMIPEXOLE – non ergot at D3PRAMIPEXOLE – non ergot at D3
• ROPINIROL – non ergot at D2 and D3ROPINIROL – non ergot at D2 and D3

13. Drugs Used in Parkinson'sDrugs Used in Parkinson's
DiseaseDisease
• Selegiline, resagilineSelegiline, resagiline
– Irreversible inhibitor of MAO B prevents dopamineIrreversible inhibitor of MAO B prevents dopamine
degradationdegradation
– Idiopathic parkinsonsIdiopathic parkinsons
– Caution in patients with peptic ulcerCaution in patients with peptic ulcer
– insomniainsomnia
– Increases efficacy of Sinemet and dose reduction ofIncreases efficacy of Sinemet and dose reduction of
the drugthe drug
– Avoid foods with thiamineAvoid foods with thiamine

14. • COMTICOMTI
• Entacapone , tolcaponeEntacapone , tolcapone
• Non- ergot derivatives that increasesNon- ergot derivatives that increases
bioavailabity of levodopa in the brainbioavailabity of levodopa in the brain
• SE: intense urine color, diarrhea,SE: intense urine color, diarrhea,
hepatocellular injuryhepatocellular injury

15. Drugs Used in Parkinson'sDrugs Used in Parkinson's
DiseaseDisease
• Benztropine,TrihexyphenidylBenztropine,Trihexyphenidyl
– Competitively inhibit postsynaptic muscarinicCompetitively inhibit postsynaptic muscarinic
receptorsreceptors
– Restores dopamine/acetylcholine balanceRestores dopamine/acetylcholine balance
– For tremor treatment with SinemetFor tremor treatment with Sinemet
– Adverse effects: sedation,confusion,memoryAdverse effects: sedation,confusion,memory
problemsproblems

16. Neurotransmitter system(s) that
may be involved in Parkinson's
disease:
A. Dopaminergic
B. Cholinergic
C. both
D. neither

17. In lower doses, this agent can be
used to treat hyperprolactinemia:
A. amantadine
B. levodopa
C. bromocriptine
D. selegiline
E. phenothiazine

18. Neurological presentations of
Parkinsonism EXCEPT:
A. rigidity
B. hyperkinesia
C. tremor
D. postural disturbances

19. Pharmacological
characteristics of L-DOPA
A. not itself pharmacologically active
B. cannot cross the blood-brain barrier
C. can be curative if initiated early enough.
D. metabolized only in the brain--due to the
presence of a unique dopa-decarboxylase

20. Anti-Parkinson Drug that
probably acts by direct dopamine
receptor stimulation
A. benztropine
B. selegiline
C. bromocriptine
D. amantadine