Drugs Used in Parkinsonism & Other Movement Disorder

ParkinsonismParkinsonism is a common movement disorder that involves dysfunction in the basal ganglia & associated brain structures

Drugs Therapy of ParkinsonismStrategies Therapy : increasing dopamine activity in the brain, decreasing muscarinic activity in the brain, or both

Drugs Therapy of ParkinsonismLevodopaThe drug is converted to dopamine by the enzyme DOPA decarboxylaseLevodopa is usually given with carbidopa (a drug that does not cross the blood-brain barrier but inhibits DOPA decarboxylase in peripheral tissue)Effects : ameliorates the sign of parkinsonism, particularly bradykinesiaToxicity :- anorexia, nausea, emesis (dose dependent)- postural hypotension, tachycardia, asystole, & cardiac arrhythmias- choreoatetosis of the face, & distal extremities, exhibit chorea, ballismus, myoclonus, tics & tremor (dyskinesias)- anxiety, agitation, confusion, delusions, hallucination, & depression (behavioral effects) Levodopa is contraindicated in patient with history of psychosis

Drugs Therapy of ParkinsonismBromocriptine & PergolideMoA : these drugs are ergot alkaloids that act as partial agonists at dopamine D2 receptors in the brainClinical Use : they have been used in patient who are refractory to or cannot tolerate levodopaToxicity :- Anorexia, nausea, & vomiting- postural hypotension, cardiac arrhythmias- dyskinesias- behavioral effects occur more commonly with bromocriptine&pergolide than with levodopa

Drugs Therapy of ParkinsonismPramipexole & ropinirolThese drugs are non-ergot dopaminee receptor agonistsThey are currently considered to be first-line drugs in the initial management of Parkinsons disease

Drugs Therapy of ParkinsonismAmantadineMoA : enhance dopaminergic neurotransmission by unknown mechanismsEffects : - improve bradykinesia, rigidity, & tremor- also has antiviral effectsToxicity :- restlessness, agitation, insomnia, confusion, hallucination, & acute toxic psychosis- peripheral edema, which responds to diuretics

Drugs Therapy of ParkinsonismSelegilineMoA : selective inhibitor of MAO type B (the enzyme isoform that metabolizes dopamine in preference to norepinephrine & serotoninClinical use : these drug is used as an adjunct to levodopa in parkinsonismToxicity : insomnia, mood changes, dyskinesias, GI distress, hypotension

Drugs Therapy of ParkinsonismEntacapone & TolcaponeMoA : inhibitors of COMT (the enzyme that converts levodopa to 3-O-methyldopa)Clinical use : this drug is used as adjuncts to levodopa-carbidopaToxicity : - dyskinesia, GI distress, postural hypotension- acute hepatic failure (tolcapone)

Drugs Therapy of ParkinsonismAcetylcholine Blocking DrugsExample: benztropine, trihexyphenidylMoA : decrease the excitatory actions of cholinergic neurons on cells by blocking muscarinic receptorsEffects : improve the tremor & rigidity of parkinsonism, but heve little effect on bradykinesiaToxicity :- CNS toxicity (drowsiness, inattention, confusion, delusions, hallucination)- peripheral adverse effects

Drug Therapy of Other Movement DisordersTremorTx : -blocking drugs (eg, propanolol)- blockers should be used with caution in patients with CHF, Asthma, diabetes, or hypoglycemia

Drug Therapy of Other Movement DisordersHuntingtons Disease & Tourettes SyndromeHuntingtons disease is an inherited disorder results from GABA functions are diminished & dopaminergic function are enhanced therapy : * amine-depleting drugs (reserpine, tetrabenazine)* dopamine receptor antagonists (haloperidol)Tourettes syndrome is a disorder of unknown cause that response to haloperidol & other dopamine D2 blockers (pimozide)

Drug Therapy of Other Movement DisordersDrug-Induced DyskinesiasParkinsonism symptoms caused by antipsychotic agentsIt is usually reversible by :- lowering dosage- change tehrapy to a drug that is less toxic to extrapyramidal function- treating with a muscarnic blocker (levodopa & bromocriptine are not useful because dopamine receptors are blocked by the antipsychotic drugs)

Drug Therapy of Other Movement DisordersWilsons DiseaseThis recessively inherited disorder of copper metabolism results in deposition of copper salts in the liver & other tissuesTx :- chelating agent penicillamine (dimethylcysteine), which removes excess copper- Toxicity : GI distress, myasthenia, opric neuropathy, & blood dyscrasias