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8/4/2019 Parkinson Drug Therapy
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13 April 2012
ANTIPARKINSON’S DRUGS
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal2
Classification
Drugs affecting brain dopaminergic system Dopamine precursor
Levodopa (l- dopa)
Dopaminergic agonists
Bromocriptine, Lisuride, Pergolide, Piribedil
Peripheral decarboxylase inhibitors Carbidopa, Benserazide
Facilitate dopaminergic transmission Amantadine, Selegiline (Deprenyl)
Drugs affecting brain cholinergic system
Central anticholinergics
Trihexyphenidyl (Benzhexol), Procyclidine, Biperidine
Antihistaminics Orphenadrine, Promethazine
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal3
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal4
LEVODOPA
95% of an oral dose is decarboxylated in the
peripheral tissues (mainly gut and liver) and
converted into DA
Only about 1-2% of administered levodopa crosses to
the brain
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Adverse Effects of Levodopa
Troublesome, dose related, reversible Nausea and vomiting, tolerance develops
Postural hypotension;Tolerance develops
Alteration in taste sensation arrythmia
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Dose of levodopa
Start with 0.25 g BD after meals,gradually increase till adequate
response is obtained
Usual dose is 2-3 g/day
LARODOPA®, LEVOPA® 0.5 g tab
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Drug Interactions with Levodopa
Pyridoxine: Abolishes therapeutic effect byenhancing peripheral decarboxylation of levodopa
Phenothiazines, butyrophenones,metoclopramide reverse therapeutic effect by
blocking DA receptors. Reserpine abolishes levodopa action by
preventing entry of DA into synaptic vesicles
Nonselective MAO inhibitors: preventdegradation of synthesis of DA and NA;
hypertensive crisis Antihypertensives: postural hypotension is
accentuated;
Atropine and other anticholinergic drugs haveadditive antiparkinsonian action with low dosesof levodopa, but retard its absorption; efficacymay be reduced
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Peripheral decarboxylase inhibitors
Carbidopa and Benserazide Extracerebral dopa-decarboxylase
inhibitors
they do not penetrate blood brain barrierand do not inhibit conversion of levodopato DA in brain
Administered along with levodopa, theyincrease its t1/2
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Benefits obtained by Levodopa +Carbidopa
Systemic concentration of DA reduced; nauseaand vomiting are not prominent
Therapeutic doses of levodopa attained quickly
Cardiac complications are minimized
Pyridoxine reversal of levodopa effect not occur
'On-off' effect is minimized since cerebral DAlevels are more sustained
Degree of improvement may be higher; somepatients, not responding adequately to levodopaalone, also improve
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Problems not resolved (or accentuated)by Levodopa + Carbidopa:
1. Involuntary movements
2. Behavioral abnormalitIes
3. Postural hypotension
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Currently levodopa always used with a decarboxylaseinhibitor, except in patients who develop markedinvoluntary movements with the combination
Combination of levodopa with carbidopa has beengiven the name 'Co-careldopa'
Tidomet -LS®,
Sinemet® 10 mg (Carbidopa) +100mg (Levodopa)
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Direct Dopaminergic Agonists
Bromocriptine, Lisuride, Pergolide
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Bromocriptine
Improvement in parkinsoniansymptoms occurs within ½ -1 hr of an
oral dose of bromocriptine; and lasts6-10 hours
High dose required, expensive and
produce intolerable side effects
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Side effects of bromocriptine
vomiting, hallucinations, hypotension,nasal stuffiness, conjunctivalinjunction
Marked fall in BP with the 'first dose'has occurred in some patients withantihypertensives
Used as a supplement to levodopa atend stages: serves to improve controland smoothen 'end of dose' and 'on-off' fluctuations
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e ec ve - n orSelegiline (Deprenyl)
Intracerebral degradation of DA is retarded
Mild antiparkinsonian action in early cases
Administered with levodopa; prolongs levodopaaction, attenuates motor fluctuations and decreases'wearing off' effect
Adjuvant to levodopa, beneficial in 50-70% patientsand permits 20-30% reduction in levodopa dose
Clinical benefits are short lived (6-26 months)
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Adverse effects of selegiline
Postural hypotension, nausea,confusion
Contraindicated in convulsive
disorders Interacts with pethidine
Excitement, hyperthermia, respiratorydepression
SELMAX®, SELGIN® 5 mg tab;
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal
AMANTADINE(dopamine releasing drug)
Fascilates the release of dopaminefrom dopaminergic neurons in brain.
Used in mild parkinsonism (less
effective) and is generally given incombination with L-Dopa.
Generally not serious: insomnia,dizziness, confusion, nightmares and
rarely hallucinations
AMANTREL® 100 mg tab
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal
CATECHOL-O-METHYL TRANSFERASE
E.g Tolcapone and entacapone. Are reversibleCOMT inhibitors.
Used as adjunct toL-Dopa-carbidopa forforadvanced cases of parkinsons disease (PD).
Combined preparation of L-Dopa+carbidopa+entacapone is available .
Adverse effects: dyskinesia,diarrhoea,confusion, hypotension and hallucinations.
Tolcapone is hepatotoxic therefore should beavoided in patients with liver disease.
Entacapone does not cause hepatotoxicity
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Dept of Pharmacology, Manipal College of Pharmaceutical Sciences Manipal
ANTICHOLINERGIC DRUGS:
E.g benzhexol, benztropine Are treatment of choice in drug
induced parkinsonism.
Act by reducing increased cholinergicactivity in striatum and have mainlyperipheral action.
Adverse effects:dry mouth confusion,blurring of vision,constipation.
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Dept of Pharmacology Manipal College of Pharmaceutical Sciences Manipal
THANK YOU
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