CENTRAL NERVOUS SYSTEM MANAGEMENT OF PARKINSON S DISEASE

Transcription

1 MANAGEMENT CENTRAL NERVOUS SYSTEM MANAGEMENT OF PARKINSON S DISEASE Parkinson s Disease is classically determined by the triad or rest tremor (usually starting in one arm) with bradykinesia (slowing of movement) and rigidity (which may manifest as cogwheel rigidity particularly in the arms). Patients often display a generalised lack of movement both in terms of facial expression and general body movement. They often have reduced arm swing (usually asymmetrical at the beginning) with festinate gait. They may have impaired ability to correct their balance. There is no treatment that has been definitely proven to slow down the progression of Parkinson s disease and therefore patients will not be adversely affected by waiting to commence treatment particularly if there is any doubt about the diagnosis. Current drug therapy aims simply to correct the chemical imbalance. Although this approach fails to prevent the progression of the disease, it greatly improves the quality and expectancy of life of most patients. About 5-10% (BNF) of patients are unresponsive to treatment. All patients should have their medication reviewed to eliminate the possibility of anti-dopaminergic drugs causing parkinsonian symptoms, for example prochlorperazine, metoclopramide, chlorpromazine, trifluoperazine, haloperidol and thioridazine. Elderly: Antiparkinsonism drugs carry a special risk of inducing confusion in the elderly. It is particularly important to initiate treatment with low doses and to use small increments REFERRAL Patients with suspected Parkinson s Disease should be referred quickly and untreated to a specialist with expertise in the differential diagnosis of this condition. [1] INITIATION OFTREATMENT Treatment for Parkinson s Disease should be initiated by specialist only. Once initiated, General Practitioners can titrate dosage according to patient s response and adverse events. 1

2 DRUG CHOICES Levodopa plus peripheral decarboxylase inhibitor preparations Co-beneldopa capsule (levodopa and benserazide) 62.5mg, 125mg, 250mg Dispersible tablet 62.5mg, 125mg Madopar CR m/r capsule 125mg Co-careldopa tablets(levodopa and carbidopa) 62.5mg, 125mg, 275mg Half Sinemet CR TM m/r tablet 25/100 Sinemet CR TM m/r tablet 50/200 Expressed as levodopa, initially mg 3 4 times daily, increased by 100 mg daily once or twice weekly according to response; ELDERLY initially 50 mg once or twice daily, increased by 50 mg daily every 3 4 days according to response. Expressed as levodopa, initially 100 mg 3 times daily, increased by mg daily or on alternate days according to response, up to 800 mg daily in divided doses Levodopa in combination with a dopadecarboxylase inhibitor is the treatment of choice for patients disabled by idiopathic Parkinson s disease. It should not be used for neurolepticinduced Parkinsonism. Levodopa therapy should be initiated with low doses and gradually increased, by small increments, at intervals of 2-3 days. The final dose is usually a compromise between increased mobility and dose-limiting side effects. Modified release preparations may help with endof-dose deterioration or nocturnal immobility and rigidity. At least 70 mg carbidopa daily is necessary to achieve full inhibition of peripheral dopadecarboxylase; co-careldopa 25/100 should therefore be used so that the daily dose of carbidopa is at least 75mg. Sudden onset of sleep: Excessive daytime sleepiness and sudden onset of sleep can occur with co-careldopa and cobeneldopa. Patients starting on treatment with these drugs should be warned of the possibility of these effects and of the need to exercise caution when driving or operating machinery. Patients, who have suffered excessive sedation or sudden onset of sleep, should refrain from driving or operating machines, until those effects have stopped. 2

3 Non-ergoline Dopamine Agonists Pramipexole Tablets 88 micrograms, 180 micrograms, 350 micrograms, 700 micrograms Ropinirole Tablet 1mg, 2mg, 5mg Starter pack Follow-on pack m/r tablets 2mg, 4mg, 8mg Rotigotine Patches 1mg, 2mg, 3mg, 4mg, 6mg, 8mg Initially 88 micrograms 3 times daily, dose doubled every 5 7 days if tolerated to 350 micrograms 3 times daily; max. 3.3 mg daily in 3 divided doses. Initially 750 micrograms daily in 3 divided doses, increase weekly by 750 micrograms to 3 mg daily; further increments of up to 3 mg at weekly intervals according to response; usual range 9 16 mg daily (but higher doses may be required if used with levodopa); max. 24 mg daily Monotherapy, 2 mg patch daily; increased in steps of 2 mg daily at weekly intervals if required; max. 8 mg/24 hours. Adjunctive therapy with levodopa, 4 mg patchdaily; increased in steps of 2 mg daily at weekly intervals if required; max. 16 mg/24 hours Doses of dopamine receptor agonists should be increased slowly according to response and tolerability. Treatment with dopamine receptor agonists should not be withdrawn abruptly. Hypotensive reactions: Hypotensive reactions can occur in some patients taking dopamine agonists; these can be particularly problematic during the first few days of treatment and care should be exercised when driving or operating machinery. Sudden onset of sleep: Excessive daytime sleepiness and sudden onset of sleep can occur with dopamine receptor agonists. Patients starting on treatment with these drugs should be warned of the possibility of these effects and of the need to exercise caution when driving or operating machinery. Patients, who have suffered excessive sedation or sudden onset of sleep, should refrain from driving or operating machines, until those effects have stopped. Compulsive behaviour: There is growing evidence that suggests a link between dopamine agonists and compulsive behaviour. Examples of compulsive behaviour: Pathological gambling; Hypersexuality; Compulsive binge eating; Compulsive shopping; Compulsive hobbyism, etc. Patients starting on treatment with these drugs should be warned of the possibility of these effects. Apomorphine Apomorphine Injection 20mg/2ml, 50mg/5ml, Apo-go pen TM By s/c injection: usual range (after initiation3 30 mg daily in divided doses By continuous s/c infusion over 12 hours: initially 1 mg/hour daily increased according to response. Should be initiated by specialist only (secondary care setting) Apomorphine is highly emetogenic; patients must receive domperidone for at least 2 days before starting treatment. Specialist supervision is advisable throughout apomorphine treatment. 3

4 Monoamine-oxidase-B inhibitors Selegiline Tablet 10 mg in the morning, or To avoid initial confusion and agitation, it 5mg, 10mg 5 mg at breakfast and may be appropriate to start treatment with Syrup 10mg in 5ml midday; Elderly initiate at a dose of 2.5 mg daily, particularly in the 2.5mg daily. elderly. Rasagiline Tablet 1mg 1mg daily Monotherapy or as an adjunct to levodopa. Catechol-O-methyltransferase inhibitors Entacapone Tablets 200mg 200 mg with each dose of levodopa with dopadecarboxylase inhibitor; max. 2 g daily Entacapone is licensed for use as an adjunct to co-beneldopa or co-careldopa for patients with Parkinson s disease who experience end-of-dose deterioration and cannot be stabilized on these combinations. It is important than Entacapone and cobeneldopa or co-careldopa are taken together at the same time of day. Concurrent levodopa dose may need to be reduced by about 10 30%. Levodopa plus peripheral decarboxylase inhibitor with entacapone Should be initiated by specialist only. Stalevo TM tablets (levodopa with carbidopa and entacapone) All strengths Only 1 tablet to be taken for each dose; See BNF for specific information for maximum dose for each strength. Useful in reducing pill burden and end-of-dose fluctuations not adequately controlled with levodopa and dopa-decarboxylase inhibitor treatment. A mixture of levodopa, carbidopa and entacapone; the proportions are expressed in the form x/y/z where x, y and z are the strengths in milligrams of levodopa, carbidopa and entacapone respectively. 4

5 Amantadine 100 mg daily increased Amantadine after one week to 100 mg Amantadine is a weak dopamine agonist with twice daily, usually in modest antiparkinsonian effects. It improves capsules conjunction with other mild bradykinetic disabilities as well as tremor 100mg, treatment; some patients and rigidity. It may also be useful for Syrup 50mg/5ml may require higher doses, dyskinesias in more advanced disease. max. 400 mg daily Antimuscarinic drugs e.g. orphenadrine, procyclidine and benxhexol (trihexyphenidyl) No longer use routinely in treatment of Parkinson s Disease because less effective that dopaminergic drugs and associated with cognitive impairment. References 1. Parkinson s Disease: Diagnosis and management in primary and secondary care (CG35) 2. The British National Formulary - Latest version 3. Summary of Product Characteristics. Access by 4. Scottish Medicine Consortiums. Access by 5