Parkinson's

1. PARKINSONISM:
 It is a chronic, progressive, motor disorder
characterized by rigidity, tremors and bradykinesia.
 Other symptoms include excessive salivation,
abnormalities of posture and gait, seborrhoea and
mood changes.
 It was described by James Parkinson in 1817 and is
therefore named after him.
 The incidence is about 1% of population above 65 years
of age.
 It is usually idiopathic in origin but can also be drug
induced.

2.  Mechanism: In idiopathic parkinsonism, there is
degeneration of nigrostiatal neurons in the basal
ganglia resulting in dopamine deficiency. The balance
between inhibitory dopaminergic neurons and
excitatory cholinergic neurons is disturbed.
 Reserpine, metoclopramide, phenothiazines can
induce parkinsonism.
 Anti parkinsonism drugs can only help to reduce the
symptoms and improve the quality of life.
 The two strategies in the treatment are:
 To enhance dopamine activity.
 To depress cholinergic overactivity.

3. CLASSIFICATION:
 Drugs that increase dopamine level:
1) DA precursor – levodopa
2) Drugs that release dopamine – amantadine
3) Dopaminergic agonists – bromocryptine, premipexol
4) Inhibit dopamine metabolism –
 MAO inhibitors – selegiline.
 COMT inhibitors – tolcapone, entacapone.
 Drugs influencing cholinergic systems:
1) Central anticholinergics: benztropine,benzhexol
2) Antihistamines: dipenhydramine, promethazine.

4. LEVODOPA:
 Though parkinsonism is due to dopamine deficiency,
dopamine is of no therapeutic value because it does
not cross the BBB.
 Levodopa is a prodrug which is converter into
dopamine in the body.
 It crossed BBB and is taken up by the surviving
nigrostraital neurons.
levodopa decarboxylase > dopamine

5.  Adverse reactions: stimulate CTZ and causes vomiting,
causes postural hypotension, tachycardia, suppresses
prolactin secretion. Nausea, palpitation, arrhythmias,
anxiety, depression, hallucinations. Abnormal
involuntary movements.
 Fluctuation of response may occur after 2-5 years
known as on-off phenomenon where patients have
alternately good response and severe disease.
 Uses: in idiopathic parkinsonism
 Drug interactions: pyridoxine enhances the peripheral
decarboxylation of levodopa and thus reduces its
availability to CNS

6. AMANTADINE:
 It is an antiviral drug.
 It enhances the release of DA in brain and diminishes
the re-uptake of DA.
 The response stars early and its adverse effects are
minor.
 Side effects: insomnia, dizziness, vomiting, postural
hypotension, hallucinations and ankle oedema.
 It is used in mild cases of parkinsonism.
 It can also be used along with levodopa.

7. BROMOCRYPTINE AND PERGOLIDE:
 These are ergot derivative having dopamine receptor
agonistic activity.
 These are longer acting drugs because of which they
are useful in treatment of on-off phenomenon.
 Adverse effects: nausea, vomiting, hallucinations and
skin eruptions. Postural hypotension, sudden
cardiovascular collapse.

8. SELIGILINE:
 Seligiline is a selective MAO-B inhibitor.
 MAO-B is present in DA containing regions of the
CNS.
 Seligiline prolongs the action of levodopa by
preventing its destruction.
 Use: seligiline may delay the progression of
parkinsonism
 Adverse effects: nausea, postural hypotension,
confusion, hallucinations.
 Uses: mild cases of parkinsonism are started on
seligiline. Also used along with levodopa.

9. COMT INHIBITORS:
 Tolcapone and entacapone inhibits the peripheral
metabolism of levodopa thereby increasing its
bioavailability.
 Tolcapone crosses BBB and enhances the availability of
levodopa to brain.
 Adverse effects: nausea, orthostatic hypotension,
confusion and hallucinations. Hepatotoxicity.

10. Anti cholinergics: the cholinergic over activity is
overcome by anticholinergics.
 Atropine derivatives like benzhexol and benzhexine
are used.
 Side effects: dry mouth, constipation, blurred vision
 Uses: adjunct to levodopa.