First choice to treat Parkinsonism

First choice to treat Parkinsonism

L-Dopa

 

Definition:

Levo-Dopa is the precursor of dopamine that bass blood brain barrier(BBB) to be converted into dopamine and increase its activity in basal ganglia to correct all syptoms of parkinsonism especially bradykinesia.

Kinetics:

L-dopa is administered orally to be absorbed by an active process in intestine(decrease by some amino acids in food), peak concentration in 1-2 hours,t1/2=1-3 hours.

*Most(more than 95%)of ingested l-dopa is metabolized in peripheral tissues by:

• DD(dopa decarboxylase) to dopamine, which cannot pass the BBB (pyridoxine"vitamin B6" activate peripheral DD,so decrease the efficacy & increase toxicity of L-dopa).
• COMT to 3-O-methyl dopa(3OMD) that complete with L-dopa for active uptake to CNS.

*Only 1-3% of ingested dose reaches CNS to be metabolized by central DD into dopamine to produce the therapeutic effect ,then metabolized br MAO-B enzyme.

Efficacy& brain level of L-Dopa is increased by adding:

• Peripheral dopa decarboxylase inhibitor(not pass BBB)as carbidopa or benserazide:-

               * Carbidopa(10 or 25 mg)+L-dopa(100 or 250 mg)=Sinemet.
               * Benserazide925mg)+ L-dopa(100 mg)=Madopar.

• COMT inhibitor as tolcapone (hepatotoxic) or entacapone.
• MAO-B inhibitor as selegiline(deprenyl) (slow disease progression).

Side effects of L-Dopa:

1. Fluctuation of response (on-off phenomenon);may be reduced by use of drug holidays& reserve l-dopa for late severe disease.
2. CNS effects: dyskinesia, psychological disturbances, hallucination, insomnia, anxiety, agitation& mood changes.
3. CVS effects: tachycardia, arrhythmia, postural hypotention.
4. GIT effects: anorexia, nusia, vomiting, peptic ulceration.
5. Other effects:mydriasis, increaso IOP, hemolysis, brown secretion.

Contraindication:

1. Psychosis.
2. Glaucoma.
3. Peptic ulcer.
4. Cardiac disease.
5. Melanoma.
6. With MAO-A inhibitor.