Syed Baseeruddin Alvi (09)
• Parkinsonism is a clinical syndrome comprising
combinations of motor problems—namely,
bradykinesia, resting tremor, rigidity, flexed posture,
“freezing,” and loss of postural reflexes.
• Studied and discovered by James Parkinson (1817)
which he called the shaking palsy and by the Latin
term paralysis agitans.
• Pathology shows loss of neuromelanin-containing
monoamine neurons, particularly dopamine (DA)
neurons in the substantia nigra pars compacta.
• Examinations reveals the presence of cytoplasmic
eosinophilic inclusions Lewy bodies in monoamine
• The loss of DA content in the nigrostriatal neurons
accounts for many of the motor symptoms which is due
to neuronal degradation
• Six cardinal clinical features of parkinsonism:
Tremor at rest Bradykinesia Loss of postural
Rigidity Flexed posture of
neck, trunk, and
Concept on pathogenesis of
The five stages of parkinson’s disease:
with minimal or
Bilateral or midline
bed or wheel
Levodopa (L-DOPA, LARODOPA, L-3,4
dihydroxyphenylalanine), the metabolic precursor of
dopamine, is the single most effective agent in the
treatment of PD .
It is inert both therapeutic & adverse effects are due
to decarboxylation , central and peripheral respectively .
In practice it is always administered in combination
with peripherally acting inhibitor of aromatic L-amino acid
decarboxylase ( carbidopa , benserazide)
Involuntary muscular twitching of the limbs or facial
muscular spasms most often affecting the tongue, jaw,
eyes, and neck
mental changes, such as depression, psychotic
episodes, paranoia, and suicidal tendencies.
less serious adverse reactions include anorexia,
nausea, vomiting, abdominal pain, dry mouth, difficulty
in swallowing, increased hand tremor, headache, and
Drugs with anticholinergic activity inhibit acetylcholine
(a neurohormone produced in excess in Parkinson’s disease)
in the CNS. Drugs with anticholinergic activity are generally
less effective than levodopa.
Dry mouth, blurred vision, dizziness, mild nausea, and
Other adverse reactions may include skin rash, urticaria
urinary retention, tachycardia, muscle weakness,
disorientation, and confusion.
These drugs prolong the effect of levodopa by blocking
(COMT). When given with levodopa, the COMT inhibitors
increase the plasma concentrations and duration of action
Disorientation, confusion, light-headedness, dizziness,
dyskinesias, hyperkinesias, nausea, vomiting, hallucinations,
Other adverse reactions are orthostatic hypotension,
sleep disorders, excessive dreaming, and muscle cramps
Dopamine receptor agonists (non ergot):
It is thought that these drugs act directly on
postsynaptic dopamine receptors of nerve cells in the
brain, mimicking the effects of dopamine in the brain.
Nausea, dizziness, postural hypotension, hallucinations,
somnolence, vomiting, confusion, visual disturbances,
abnormal involuntary movements, and headache.
Selective MAO-B Inhibitors:
By interfering with one of the enzymes that break
down dopamine (monoamine oxidase, or MAO-B),
they can enhance and prolong the effect of each