Drugs Used in Parkinsonism &

Other Movement Disorder

Parkinsonism

Parkinsonism is a common movement

disorder that involves dysfunction in
the basal ganglia & associated brain
structures

Drugs Therapy of Parkinsonism

Strategies Therapy : increasing

dopamine activity in the brain,
decreasing muscarinic activity in the
brain, or both

Drugs Therapy of Parkinsonism

Levodopa

The drug is converted to dopamine by the enzyme DOPA

decarboxylase

Levodopa 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

bradykinesia

Toxicity :
- 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 Parkinsonism

Bromocriptine & Pergolide
MoA : these drugs are ergot alkaloids that act as
partial agonists at dopamine D2 receptors in the brain
Clinical Use : they have been used in patient who are
refractory to or cannot tolerate levodopa
Toxicity :
- Anorexia, nausea, & vomiting
- postural hypotension, cardiac arrhythmias
- dyskinesias
- behavioral effects occur more commonly with
bromocriptine&pergolide than with levodopa

Drugs Therapy of Parkinsonism

Pramipexole & ropinirol
These drugs are non-ergot dopaminee
receptor agonists
They are currently considered to be
first-line drugs in the initial
management of Parkinsons disease

Drugs Therapy of Parkinsonism

Amantadine
MoA : enhance dopaminergic neurotransmission by
unknown mechanisms
Effects :
- improve bradykinesia, rigidity, & tremor
- also has antiviral effects
Toxicity :
- restlessness, agitation, insomnia, confusion,
hallucination, & acute toxic psychosis
- peripheral edema, which responds to diuretics

Drugs Therapy of Parkinsonism

Selegiline
MoA : selective inhibitor of MAO type B (the
enzyme isoform that metabolizes dopamine in
preference to norepinephrine & serotonin
Clinical use : these drug is used as an adjunct
to levodopa in parkinsonism
Toxicity : insomnia, mood changes,
dyskinesias, GI distress, hypotension

Drugs Therapy of Parkinsonism

Entacapone & Tolcapone
MoA : inhibitors of COMT (the enzyme that
converts levodopa to 3-O-methyldopa)
Clinical use : this drug is used as adjuncts to
levodopa-carbidopa
Toxicity :
- dyskinesia, GI distress, postural hypotension
- acute hepatic failure (tolcapone)

Drugs Therapy of Parkinsonism

Acetylcholine Blocking Drugs
Example: benztropine, trihexyphenidyl
MoA : decrease the excitatory actions of cholinergic
neurons on cells by blocking muscarinic receptors
Effects : improve the tremor & rigidity of parkinsonism,
but heve little effect on bradykinesia
Toxicity :
- CNS toxicity (drowsiness, inattention, confusion,
delusions, hallucination)
- peripheral adverse effects

Drug Therapy of Other

Movement Disorders
Tremor
Tx : -blocking drugs (eg, propanolol)
- blockers should be used with
caution in patients with CHF, Asthma,
diabetes, or hypoglycemia

Drug Therapy of Other

Movement Disorders
Huntingtons Disease & Tourettes Syndrome
Huntingtons 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 Disorders
Drug-Induced Dyskinesias
Parkinsonism symptoms caused by
antipsychotic agents
It 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 Disorders
Wilsons Disease
This recessively inherited disorder of copper
metabolism results in deposition of copper
salts in the liver & other tissues
Tx :
- chelating agent penicillamine
(dimethylcysteine), which removes excess
copper
- Toxicity : GI distress, myasthenia, opric
neuropathy, & blood dyscrasias