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ANTI-PARKINSONIAN
DRUGS
Parkinsonism
• It is a common movement disorder that
involves dysfunction in the basal ganglia
and associated brain structures.
The signs include:
• rigidity of skeletal muscles.
• akinesia(or bradykinesia or hypokinesia).
• flat facies.
• tremor at rest.
There are two types of parkinsonism:
Idiopathic parkinsonism:
• In which the pathologic characteristics include a
decrease in the levels of dopamine and the
degeneration of dopaminergic neurons.
• The reduction of normal dopaminergic
neurotransmission leads to excessive excitatory
actions of cholinergic neurons,thus dopamine
and acetylcholine activities are out of balance in
parkinsonism.
Drug induced parkinsonism:
Many drugs can cause symptoms of parkinsonism,these
effects are usually reversible.
The most important are:
• The butyrophenone and phenothiazine anti-psychotic
drugs,which block brain dopamine receptors.
• Reserpine at high doses causes silimar symptoms,by
depleting brain dopamine stores.
• Cholinesterase inhibitors,by increasing cholinergic
activity.
Drug therapy of parkinsonism:
• Strategies of drug treatment of
parkinsonism involve increasing dopamine
activity in the brain or decreasing
muscarinic cholinergic activity in the brain.
• It should be noted that parkinsonism is a
chronic progressive disease,and that
treatment is only symptomatic.
• Though treatment does not stop the
progress of the disease,it improves the
quality and expectancy of life in most
patients.
1.Levodopa:
• Dopamine does not readily cross the blood
brain barrier,its precursor levodopa is
used,this amino acid is converted to
dopamine by the enzyme dopa
decarboxylase,which is present in many
tissues including the brain.
• Levodopa is usually given with
carbidopa(dopa decarboxylase inhibitor),a
drug that does not cross the blood brain
barrier,but inhibits dopa decarboxylase in
peripheral tissues.
• With this combination,lower doses of
levodopa are needed(effective) and there
are fewer peripheral side effects.
• Levodopa is the drug of choice in severe
parkinsonism,it can reduce
hypokinesia,rigidity and tremor,it is less
effective in post-encephalitic parkinsonism
and should be avoided in drug induced
parkinsonism.
Side effects:
• G.I.T. anorexia,nausea,vomiting.
• C.V.S. postural hypotension,tachycardia,
asystole,cardiac arrhythmias.
• dyskinesia.
• behavioral:
anxiety,agitation,confusion,delusion,hallucinations,depression.
• Levodopa may sometimes lose its effectiveness
after several months of therapy and the patient
experiences marked swings from mobility to total
immobility(referred to as on-off effect),this
fluctuating disability may last several minutes or
hours.
• These changes appear to be related to
blood levels of dopa,high doses may
induce dyskinesia and low doses may
induce immobility(akinesia).
• In the later case(akinesia) increasing the
dose frequency may be helpful and adding
bromocriptine may be useful.
2.Bromocriptine:
• It acts as an agonist at dopamine
receptors in the brain.
• It can relieve akinesia,rigidity,and tremor.
• It is less effective than levodopa but has a
longer duration of action and causes less
dyskinesia.
• It is used as an individual drug, in
combination with levodopa(and with anticholinergic drugs)and in patients who
cannot tolerate levodopa.
Side effects:
• G.I.T. anorexia,nausea,vomiting.
• C.V.S. postural hypotension,cardiac
arrhythmias.
• dyskinesia.
• behavioral:confusion,hallucinations,delusio
-ns.
• miscellaneous: pulmonary infiltrates.
3.Amantadine:
• Enhances dopaminergic
neurotransmission by unknown
mechanism that may involve increasing
synthesis or release of dopamine or
inhibition of reuptake of dopamine,the drug
has also muscarinic blocking actions.
• Amantadine may improve
bradykinesia,rigidity and tremor,but is
usually effective for only a few weeks.
• Amantadine has also anti-viral effects.
Side effects:
• behavioral:
restlessness,agitation,insomnia,confusion,
hallucinations and acute toxic psychosis.
• miscellaneous: G.I.T. disturbances,urinary
retention and postural hypotension.also
may cause peripheral edema that
responds to diuretics.
4.Selegiline:
• It is a selective inhibitor of MAO type B,which is
the enzyme that metabolizes dopamine.
• Selegiline may increase brain dopamine levels.
• The drug is used as an adjunct with levodopa in
parkinsonism and also has been used as the
sole agent in newly diagnosed patient.
Side effects:
• Insomnia,mood
changes,dyskinesia,G.I.T.distress,hypoten
-sion.
5.Entacapone and Tolcapone:
• They are inhibitors of catechol-o-methyl
transferase(comt),the enzyme that converts
levodopa to 3-o-methyl dopa(3-o-md).
• Increased plasma levels of (3-o-md) are
associated with poor response to
levodopa,partly because the compound
competes with levodopa for active transport into
the C.N.S.
• The drugs are used as adjuncts to
levodopa-carbidopa,improving and
prolonging the response to therapy.
Side effects:
• Dyskinesia,G.I.T.distress,postural
hypotension,hepatic failure.
6.Acetylcholineblocking(antimuscarinic)drugs:
• These drugs decrease the excitatory
actions of cholinergic neurons by blocking
muscarinic receptors.
• Drugs such as benztropine or
trihexyphenidyl may improve the tremor
and rigidity of parkinsonism but have little
effect on bradykinesia.
• Anti-cholinergics are particularly valuable
in the treatment of parkinsonism induced
by anti-psychotics(phenothiazines) and
metoclopramide and in patients with postencephalitic parkinsonism.
Side effects:are that of acetylcholine
blocking drugs.
• C.N.S.
drowsiness,inattention,confusion,delusions
,hallucinations.
• peripheral: are typical of atropine like
drugs.
• Anti-cholinergics may be combined with
amantadine and in severe cases with
levodopa.
• The dose of anti-cholinergics should be
increased gradually(every3-5days) to
avoid or minimize the side effects.