1. ANTI-PARKINSONIAN DRUGS

2. Parkinsonism It is a common movement disorder that involves dysfunction in the basal ganglia and associated brain structures.

3. The signs include: rigidity of skeletal muscles. akinesia(or bradykinesia or hypokinesia). flat facies. tremor at rest.

4. There are two types of parkinsonism: Idiopathic parkinsonism: In which the pathologic characteristics include a decrease in the levels of dopamine and the degeneration of dopaminergic neurons. The reduction of normal dopaminergic neurotransmission leads to excessive excitatory actions of cholinergic neurons,thus dopamine and acetylcholine activities are out of balance in parkinsonism.

5. Drug induced parkinsonism: Many drugs can cause symptoms of parkinsonism,these effects are usually reversible. The most important are: The butyrophenone and phenothiazine anti-psychotic drugs,which block brain dopamine receptors. Reserpine at high doses causes silimar symptoms,by depleting brain dopamine stores. Cholinesterase inhibitors,by increasing cholinergic activity.

6. Drug therapy of parkinsonism: Strategies of drug treatment of parkinsonism involve increasing dopamine activity in the brain or decreasing muscarinic cholinergic activity in the brain. It should be noted that parkinsonism is a chronic progressive disease,and that treatment is only symptomatic.

7. Though treatment does not stop the progress of the disease,it improves the quality and expectancy of life in most patients.

8. 1.Levodopa: Dopamine does not readily cross the blood brain barrier,its precursor levodopa is used,this amino acid is converted to dopamine by the enzyme dopa decarboxylase,which is present in many tissues including the brain.

9. Levodopa is usually given with carbidopa(dopa decarboxylase inhibitor),a drug that does not cross the blood brain barrier,but inhibits dopa decarboxylase in peripheral tissues. With this combination,lower doses of levodopa are needed(effective) and there are fewer peripheral side effects.

10. Levodopa is the drug of choice in severe parkinsonism,it can reduce hypokinesia,rigidity and tremor,it is less effective in post-encephalitic parkinsonism and should be avoided in drug induced parkinsonism.

11. Side effects: G.I.T. anorexia,nausea,vomiting. C.V.S. postural hypotension,tachycardia, asystole,cardiac arrhythmias. dyskinesia.

12. behavioral: anxiety,agitation,confusion,delusion,hallucinatio- ns,depression. Levodopa may sometimes lose its effectiveness after several months of therapy and the patient experiences marked swings from mobility to total immobility(referred to as on-off effect),this fluctuating disability may last several minutes or hours.

13. These changes appear to be related to blood levels of dopa,high doses may induce dyskinesia and low doses may induce immobility(akinesia). In the later case(akinesia) increasing the dose frequency may be helpful and adding bromocriptine may be useful.

14. 2.Bromocriptine: It acts as an agonist at dopamine receptors in the brain. It can relieve akinesia,rigidity,and tremor. It is less effective than levodopa but has a longer duration of action and causes less dyskinesia.

15. It is used as an individual drug, in combination with levodopa(and with anti- cholinergic drugs)and in patients who cannot tolerate levodopa.

16. Side effects: G.I.T. anorexia,nausea,vomiting. C.V.S. postural hypotension,cardiac arrhythmias. dyskinesia. behavioral:confusion,hallucinations,delusio -ns. miscellaneous: pulmonary infiltrates.

17. 3.Amantadine: Enhances dopaminergic neurotransmission by unknown mechanism that may involve increasing synthesis or release of dopamine or inhibition of reuptake of dopamine,the drug has also muscarinic blocking actions.

18. Amantadine may improve bradykinesia,rigidity and tremor,but is usually effective for only a few weeks. Amantadine has also anti-viral effects.

19. Side effects: behavioral: restlessness,agitation,insomnia,confusion, hallucinations and acute toxic psychosis. miscellaneous: G.I.T. disturbances,urinary retention and postural hypotension.also may cause peripheral edema that responds to diuretics.

20. 4.Selegiline: It is a selective inhibitor of MAO type B,which is the enzyme that metabolizes dopamine. Selegiline may increase brain dopamine levels. The drug is used as an adjunct with levodopa in parkinsonism and also has been used as the sole agent in newly diagnosed patient.

21. Side effects: Insomnia,mood changes,dyskinesia,G.I.T.distress,hypoten -sion.

22. 5.Entacapone and Tolcapone: They are inhibitors of catechol-o-methyl transferase(comt),the enzyme that converts levodopa to 3-o-methyl dopa(3-o-md). Increased plasma levels of (3-o-md) are associated with poor response to levodopa,partly because the compound competes with levodopa for active transport into the C.N.S.

23. The drugs are used as adjuncts to levodopa-carbidopa,improving and prolonging the response to therapy.

24. Side effects: Dyskinesia,G.I.T.distress,postural hypotension,hepatic failure.

25. 6.Acetylcholine- blocking(antimuscarinic)drugs: These drugs decrease the excitatory actions of cholinergic neurons by blocking muscarinic receptors.

26. Drugs such as benztropine or trihexyphenidyl may improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia.

27. Anti-cholinergics are particularly valuable in the treatment of parkinsonism induced by anti-psychotics(phenothiazines) and metoclopramide and in patients with post- encephalitic parkinsonism.

28. Side effects:are that of acetylcholine blocking drugs. C.N.S. drowsiness,inattention,confusion,delusions,hallucinations. peripheral: are typical of atropine like drugs.

29. Anti-cholinergics may be combined with amantadine and in severe cases with levodopa. The dose of anti-cholinergics should be increased gradually(every3-5days) to avoid or minimize the side effects.