understanding the parkinson's disease

Parkinson’s disease

by Syed Baseeruddin Alvi (09)

INTRODUCTION• 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

neurons.

• 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

reflexes

Rigidity Flexed posture of neck, trunk, and limbs

Freezing phenomenon

Concept on pathogenesis of Parkinson’s disease.

The five stages of parkinson’s disease:

Stage 1:Unilateral involvement only with minimal or no functional impairment

Stage 2:Bilateral or midline involvement, without balance impairment

Stage 3:Impairment of righting reflex

Stage 4:Fully developed and severely disabling

Stage 5:Confinement to bed or wheel chair.

Pathogenesis of PD:

Pathogenesis of PD:

Pathogenesis of PD:

Drugs used in treatment of PD:

Dopamine precursor:

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)

Site of action:

Adverse reactions:

Involuntary muscular twitching of the limbs or facial

muscles

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

dizziness.

Anticholinergic drugs:

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.

Adverse reactions:

Dry mouth, blurred vision, dizziness, mild nausea, and

nervousness.

Other adverse reactions may include skin rash, urticaria

urinary retention, tachycardia, muscle weakness,

disorientation, and confusion.

COMT inhibitors:

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

of levodopa.

Adverse reactions:

Disorientation, confusion, light-headedness, dizziness,

dyskinesias, hyperkinesias, nausea, vomiting, hallucinations,

and fever

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.

Adverse reactions:

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

dopamine molecule.

Treatment:

Surgical Therapy: