1. Anti Parkinson's Drugs Parkinsonism
A neurological syndrome usually resulting from deficiency of the neurotransmitter dopamine as the consequence of degenerative, vascular, or inflammatory changes in the basal ganglia.
Characterized by rhythmical muscular tremors, rigidity of movement, bradykinesia, droopy posture.

2. Coronal slices of human brain showing the basal ganglia
Coronal slices of human brain showing the basal ganglia. ROSTRAL: striatum, globus pallidus (GPe and GPi) CAUDAL: subthalamic nucleus (STN), substantia nigra (SN)

3. Signs
Remember RAFT
R = rigidity of skeletal muscles A = akinesia (loss of voluntary movement) F = flat facies T = tremor at rest (not always)

4. CLASSIC FEATURES SHUFFLING GAIT STOOPING POSTURE DECREASED ARM SWING
TURNING EN BLOC
DYSPHONIA
MOOD DISTURBANCES
SLEEP DISTURBANCES
MEMORY LOSS

6. P E T SCAN

7. Secondary Parkinsonism
Sometimes parkinsonism like symptoms follow after viral encephalitis or multiple vascular lesions.
Phenothiazines and Haloperidol – action block dopamine receptors – may produce Parkinson's symptoms.
Strictly not used in the pt.’s with parkinsonism.

9. Dopamine Dopamine: does not cross: blood-brain barrier
ineffective if administered peripherally

10. Drugs used Levodopa Carbidopa Bromocriptine Amantadine
Anticholinergic agents
Deprenyl ( Selegiline)

11. Levodopa L-DOPA: metabolic precursor of dopamine enters the brain
decarboxylation to dopamine

12. L-DOPA Rapid absorption from small intestine, influenced by:
gastric emptying rate
local pH
Food– avoid heavy meals
Excretion : urine
Amount reaching brain : very less
Rest : peripheral decarboxylation to dopamine.

13. To achieve therapeutic brain levels, either:
Large quantities to be given
With a dopa decarboxylase inhibitor, such as Carbidopa
Carbidopa does not penetrate BBB

14. Clinical Use :Levodopa
Does not stop disease progression
May reduce Parkinson's disease mortality rate
Most effective in diminishing bradykinesia

15. Adverse Effects :Levodopa
GIT ; vomiting, tolerance develops.
CVS : Tachycardia, Ventricular extra systoles
MC : Postural/orthostatic hypotension
HTN : if large doses taken
Arrhythmias
Dyskinesias
MC: Choreoathetosis

16. Behavioral Effect : depression, agitation, insomnia , anxiety, confusion, delusions
Precipitation/worsening: Gout
 Mydriasis– adrenergic action

17. Contraindications Psychotic patients Angle-closure glaucoma
History of melanoma/suspicious undiagnosed skin lesions.
Vit. B-6.- increases peripheral breakdown
Careful management : CVS disease, PUD
Not with MAO – I > HTN crisis.

18. Carbidopa
Peripheral decarboxylase inhibitor which doesn't cross the BBB
To decrease peripheral decarboxylation of
L-dopa.
Carbidopa leads to decreased side-effects and decreased dosage of L-dopa required.

20. Dopamine Agonists Directly activate dopamine receptors
Not requiring enzymatic activation
Bromocriptine

21. Clinical Use :Bromocriptine
Compared with Levodopa:
Less incidence of response fluctuation and Dyskinesias
Adverse Effects
GIT : nausea, vomiting
Peptic ulceration with bleeding
CVS : postural hypotension
Behavioural : confusion, hallucinations, delusions

22. Contraindications History/presence of psychosis
Recent myocardial infarction
Relative contraindications :
Peripheral vascular disease or peptic ulcer

23. Monoamine Oxidase Inhibitors
MAO-A :  serotonin/ norepinephrine
MAO-B :  metabolizes dopamine
Selegiline : Selective MAO - B inhibitor
Adjunctive treatment to L-DOPA
C I :
Meperidine
Tricyclic antidepressants
 SSRI

24. Amantadine Antiviral drug Mechanism of action: unclear Clinical Use
Short-term benefits; less potent Levodopa
Improves rigidity, tremor, bradykinesia

25. Adverse Effect Hallucinations, confusion, irritability, depression
Over dosage: acute psychosis
Livedo reticularis: -- reddish blue skin mottling, affecting extremities
CHF, orthostatic hypotension , peripheral edema
GIT: nausea, vomiting
With caution : CHF, convulsions.

26. Anticholinergics Clinical Use Improvement: rigidity/tremor
Minor effect: bradykinesia

27. Benztropine
Biperiden
Orphenadrine
Procyclidine
Trihexyphenidyl
CI :
Prostatic hyperplasia
Obstructive gastrointestinal disease

28. Catechol o methyl tranferace inhibitors
When peripheral dopamine decarboxylase activity is inhibited, a significant amount of methyl dopa is formed which competes with levodopa for active transport into the CNS.
Inhibition of COMT by Tolcapone /entacapone leads to increased central uptake of levodopa.

29. Physiologic postural tremor (normal)
Drug-Induced–
Bronchodilators
Tricyclic antidepressants
Lithium
Rx : Propranolol.

30. Chorea Dopaminergic nigrostriatal pathway over activity
Anti-Dopaminergic agents:
Reserpine
Phenothiazines and Butryophenones (haloperidol)

32. DRUGS USED IN ALZHEIMER DISEASE
Alzheimer dementia 3 distinguishing features
Accumulation of senile plaques
Neurifibrillary tangles
Loss of cortical neurons –cholinergic
Drugs used—inhibition of acetyl choline esterace
Donepezil, galantamine, rivastigmine & tacrine
Galantamine competitive inhibitor
Tacrine--hepatotoxic

33. NMDA receptor antagonist
Antagonist of NMDA receptors are neuroprotective
Memantine—slows the rate of memory loss
Prevents loss of neurons

34. DRUGS USED IN MULTIPLE SCLEROSIS
MS is an autoimmune inflammatory demyelinating disease of the CNS.
Corticosteroids for acute attacks have been used
Cyclophosphamide and azathioprine can also be tried
Newer drugs interferon beta 1a and 1b
Mitoxantrone, Dalfampridine and fingolimod are also used now