Effects of long term Levodopa therapy are

Ans. is 'd' i.e., All the above Adverse effects of prolonged use of levodopa o Abnormal movements: Facial tics, grimacing, tongue thrusting, choreo-athetoid movements of limbs start appearing after a few months of use of levodopa at optimum therapeutic dose and progress with time to include practically all patients. No tolerance develops to this adverse effect, but dose reduction decreases severity. Abnormal movements may become as disabling as the original disease itself-are the most important dose-limiting side effects. o Behavioral effects: Range from mild anxiety, nightmares, etc. to severe depression, mania, hallucinations, mental confusion or frank psychosis. Excessive DA action in the limbic system is probably responsible (antidopaminergic drugs are antipsychotic). o Fluctuation in motor performance: After 2-5 years of therapy, the level of control of parkinsonian symptomatology starts showing fluctuation. 'End of dose' deterioration (wearing off) which is initially gradual, develops into rapid 'switches' or on-off effect.With time 'all or none' response develops, i.e. the patient is alternately well and disabled. Abnormal movements may jeopardize even the 'on' phase. This is probably a reflection of progression of the disorder: with progressive degeneration of DA neurons the ability to regulate storage and release of DA may be largely lost: DA is then synthesized in the striatum on a moment to moment basis resulting in rapid and unpredictable fluctuations in motor control. Dose fractionation and more frequent administration tend to diminish these for a time.