ANTIPARKINSONIAN DRUGS CLASS MBBS .pptx

ANTIPARKINSONIAN DRUGS

1. ANTIPARKINSONIAN DRUGS DR.V.VIGNESH MD ASSISTANT PROFESSOR BMCH

2. PARKINSONISM DISEASE It is an extrapyramidal motor disorder characterized by rigidity,tremor and hypokinesia with secondary manifestations like defective posture & gait,mask like facies and sialorrhoea;dementia may accompany

3. LEVODOPA Prodrug 95% of an oral dose is decarboxylated in the peripheral tissue ( mainly gut and liver ) 1 – 2 % of administered levodopa crosses to the brain,taken up by the surviving dopaminergic neurons,converted into dopamine which is stored and released as a transmitter DOSE : 200 – 1000 mg per day

4. ADVERSE EFFECTS Frequent Dose related AT THE INITIATION OF THERAY Nausea and vomiting Postural hypotension Cardiac arrhythmias Exacerbation of angina Alteration in taste sensation

5. AFTER PROLONGED THERAPY Abnormal movements ( dyskinesia ) Facial tics,grimacing,tongue thrusting,chorea athetoid movement of limbs Most important dose limiting side effects Their intensity corresponds with levodopa levels No tolerance develops

6. 2.Behavioural effects Range from mild anxiety,night mares etc to severe depreesion , mania,hallucination,mental confusion or frank psychosis Excessive dopamine action in the limbic system Contraindicated in patients with psychotic illness 3.Fluctuation in motor performance

7. INTERACTIONS Pyridoxine Phenothiazines , butyrophenones,metoclopramide Reserpine Non selective MAO inhibitors Antihypertensive drugs Atropine & antiparkinsonian anticholinergic drugs

8. PERIPHERAL DECARBOXYLASE INHIBITORS Carbidopa & benserazide BENEFITS Plasma t ½ of L Dopa is prolonged Systemic concentration of DA is reduced Cardiac complications are minimized Pyridoxine reversal of L Dopa effect does not occur On & Off effect is minimized Degree of improvement may be higher

9. Problems not resolved or accentuated are Involuntary movements Behavioural abnormalities Excessive day time sleepiness Postural hypotension

10. DOPAMINERGIC AGONISTS BROMOCRIPTINE Ergot derivative Potent agonist on D2 receptor Partial agonist or antagonist on D1 receptor ADVERSE EFFECTS: Vomiting, hallucination, hypotension, nasal stiffness, conjunctival injection. DOSE: Initial dose is 1.25mg HS. Increased as need upto 5mg TDS.

11. Ropinirole and Pramipexole Selective D2 and D3 receptor agonists Monotherapy for early PD SIDE EFFECTS: Nausea, dizziness, hallucinations, hypotension, day time sleep. DOSE: Ropinirole-Starting dose is 0.25mg TDS titrated to a max of 4-8mg TDS. Early cases generally require 1-2mg TDS. Pramipexole-0.125 mg TDS titrated to 0.5 to 1.5mg TDS.

12. MAO-B inhibitors Selegiline selective and irreversible MAO B inhibitor Responsible for the therapeutic effect in parkinsonism Selegiline alone has mild antiparkinsonism action in early cases ADVERSE EFFECTS : postural hypotension,nausea,confusion,accentuation of levodopa induced involuntary movements and psychosis DOSE : 5 mg with breakfast and with lunch,either alone or with levodopa/carbidopa Contraindicated in convulsive disorders

13. 2.RASAGILINE 5 times more potent Longer acting DOSE : 1 mg od in the morning

14. COMT INHIBITORS Entacapone & Tolcapone Selective,potent and reversible Prolong the half life of levodopa and allow larger fraction of administered dose to cross bbb . Preserve dopamine formed in the straited and supplement the peripheral effect. Useful in advanced and fluctuating PD along with Levodopa-carbidopa. Not indicated in early PD cases.

15. ADVERSE EFFECTS: Nausea, vomiting, dyskinesia, postural hypotension, hallucinations, diarrhoea, yellow-orange discolouration of urine. DOSE: Entacapone- 200mg with each dose of levodopa-carbidopa; max dose-1600mg/day. Tolcapone- 100-200 mg BD or TDS.

16. NMDA receptor antagonist Dopamine facilitator Amantadine: It promotes pre synaptic synthesis and release of dopamine in the brain and has anti cholinergic property. Can be used in milder cases or in short courses to supplement levodopa for advanced cases. DOSE: 100mg BD. SIDE EFFECTS: Insomnia, restlessness, anti cholinergic effects rarely hallucinations, livedo reticularis, edema of ankle.

17. Central Anti cholinergics They act by reducing the unbalanced cholinergic activity in the straitum of parkinsonism patients. Tremor is benefited more than rigidity. Hypokinesia is affected the least. Sialorrhoea is controlled their peripheral action. Only drugs used in drug induced parkinsonism. Side effects are similar to atropine. EXAMPLES: Trihexyphenidyl- Start with 2-3mg in divided doses/day.

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