None of the above drugs alter the basic pathology of PD—the disease continues to progress. Drugs only provide symptomatic relief and give most patients an additional 3–6 years of happier and productive life.
SOME GENERAL POINTS
1. None of the above drugs alter the basic pathology of PD—the
disease continues to progress. Drugs only provide symptomatic relief and give
most patients an additional 3–6 years of happier and productive life.
Considering that oxidative metabolism of DA generates free
radicals which may rather hasten degeneration of nigrostriatal neurones, it has
been argued that levodopa therapy might accelerate progression of PD. There is
no proof yet for such a happening, but nevertheless it may justify use of
anticholinergics/selegiline or newer direct DA agonists in early/mild cases.
2. Initially, when disease is mild, only anticholinergics or
selegiline may be sufficient. Monotherapy with newer DA agonists ropinirole or
pramipexole is being increasingly employed for early cases. Selegiline may also
be combined with levodopa during the deterioration phase of therapy to overcome
‘wearing off’ effect.
3. Combination of levodopa with a decarboxylase inhibitor is the
standard therapy, and has replaced levodopa alone. Slow and careful initiation
over 2–3 months, increasing the dose as tolerance to early side effects develops
and then maintenance at this level with frequent evaluation gives the best
results. Full benefit lasts for about 2–3 years, then starts declining.
4. Subsequently the duration of benefit from a
levodopa dose progressively shortens—end of dose ‘wearing off’ effect is seen.
Dyskinesias appear, mostly coinciding with the peak of levodopa action after
each dose. Relief of parkinsonian symptoms gets linked to the production of
dyskinesias. Still later (4–8 years) the ‘on-off’ phenomena and marked dyskinesias
may become so prominent that the patient is as incapacitated with the drug as
without it. However, withdrawal of levodopa may precipitate marked rigidity,
hampering even respiratory excursions.
5. Combination of levodopa with decarboxylase
inhibitor increases efficacy and reduces early but not late complications.
6. Levodopa alone is now used only in those
patients who develop intolerable dyskinesias with a levodopa-decarboxylase
inhibitor combination.
7. Amantadine may be used with levodopa for brief
periods during exacerbations.
8. The direct DA agonists bromocriptine or
ropinirole/pramipexole are commonly used to supplement levodopa in late cases
to smoothen ‘on off’ phenomenon, to reduce levodopa dose and possibly limit
dyskinesias.
9. In advanced cases, the COMT inhibitor
entacapone may be added to levodopa-carbidopa to prolong its action and subdue
‘on off’ fluctuation. It can be given to patients receiving selegiline or DA
agonists as well.
10. Withdrawal of levodopa for 4–21 days (drug
holiday) to reestablish striatal sensitivity to DA by increasing dopaminergic
receptor population has now been given up.
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