Parkinson Disease

Medical Management of Parkinsonism : 

Medical Management of Parkinsonism Parkinsonism is due to progressive destruction of Dopmaninergic neurons in Nirgrostriatal system. Drugs do not cure but if properly used can greatly improve quality of life in this chronic degenerative disorder.

Two balanced Systems at EPS : 

Two balanced Systems at EPS Dopamine is inhibitory NTS Acetylcholine is excitatory NTS Normally there is good balance in their activity. Dopamine deficiency is associated with Ach overactivity.

To maintain the balance : 

To maintain the balance Reduce cholinergic activity by giving antimuscarinic drugs Enhance dopaminergic activity by giving dopamine precursors or dopamine agonists.

Approaches to restore normal dopaminergic/ cholinergic balance : 

Approaches to restore normal dopaminergic/ cholinergic balance Prolong the action of Dopamine by selective inhibition of metabolism by Selegelline( MAOB) or Taclopine (Tasmar) on COMT.

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Supplying Levodopa as precursor and prevent it’s peripheral metabolism by combining with Dopa decarboxylase inhibitors.

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Giving dopamine agonists (Bromocriptine)

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Increase release of DA from stores and inhibit it’s reuptake Give Anticholinergic drugs.

Drugs which can precipitate or worsen Parkinsonism : 

Drugs which can precipitate or worsen Parkinsonism Anticholinesterases ( Increase Ach ) Dopamine depletion ( Reserpine and similar drugs) Dopamine antagonists (Neuroleptic drugs)

Dopaminergic Drugs: Levodopa and Carbidopa : 

Dopaminergic Drugs: Levodopa and Carbidopa Dopamine does not cross BBB, so Levodopa is used as precursor. Levodopa is destroyed by peripheral metabolism by Dopa decarboxylase. To prevent destruction, it is used seldom alone but often in combination with Carbidopa (SINEMET) or benserazide (MADOPAR).

Levodopa : 

Levodopa Particularly effective in tremors and akinesia. It is well absorbed by small intestines through Active Transport. Adverse effects include nausea and vomiting (CRTZ), Postural hypotension (D1) Mental changes Cardiac Dysrrhythmias

Therapeutic Use of Levodopa : 

Therapeutic Use of Levodopa Levodopa alone or in combination of dopa decarboxylase inhibitors is introduced gradually. Dose increased every week. A compromise is reached between therapeutic benefit and adverse effects. Complince is important to prevent relapse.

Amantadine : 

Amantadine It appears to act by increasing synthesis and release of Dopamine and by inhibiting neuronal reuptake. Much less effective than levodopa. Advantages include simplicity in use (once a day) and comparative freedom from ADRs.(CNS disturbances do occur)

Bomocriptine : 

Bomocriptine Ergot alkaloid and partial dopamine agonist. Commonly used with levodopa Absorption is rapid so combination can be beneficial in patients who experience end of dose effect. Lysuride and Pergolide are similar to Bromocriptine. Apomorphine is also PA on DA receptors

Monoamine Oxidase and COMT Inhibitors : 

Monoamine Oxidase and COMT Inhibitors Selegelline: is selective MAOB inhibitor. It therefore does not create risk of hypertensive crisis. It has however adverse effects related to dopamine overactivity. Tolcapine (Tasmar) is COMT inhibitor which is recently approved. It is effective in moderate degree disease. Hepatotoxicity may occur as serious limitation.

Anticholinergic drugs : 

Anticholinergic drugs Benztropin Benzhexol Procyclidine There is little to choose from on the basis of efficacy. These drugs produce modest improvements in tremors and rigidity but little in hypokinesia.

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Algorithm of Treatment of Early stage of Parkinson Disease

Supportive Treatment : 

Supportive Treatment Antipsychotic treatment: Clozapine Depression: Nortryptilline or Desipramine Anxiety and Panic attacks: Buspirinone Confusion and dementia: Donezepil Hypotension: Fludrocortisone Surgical treatment: Ventrolateral thalamotomy or palidotomy may be effective in selective patients