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Parkinsons 19.8-Dr Sravanthi

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23 views20 pages

Parkinsons 19.8-Dr Sravanthi

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doc.kas14
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© © All Rights Reserved
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MOVEMENT DISORDERS

DR.Y.SRAVANTHI
General
Medicine
Post Graduate
1st year
Topic

• 19.8 Discuss and describe the


pharmacology, dose, side effects
and interactions used in the drug
therapy of Parkinson's syndrome
PARKINSONISM

Definition:
• Parkinsonism is a progressive neurological disorder
of muscle movement as a clinical syndrome
consisting of 4 cardinal features:
• 3) bradykinesia (slowness of movement) and, in
extreme cases, a loss of physical movement
(akinesia)
• 4) muscular rigidity
• 5) resting tremor (which usually disappears during
voluntary movement)
• 6) impairment of postural balance leading to
disturbances of gait and falling
AntiParkinsonian Drugs
Drugs used in the treatment of
parkinsonism_ 1. Levodopa
Levodopa is (the most effective drug used in the treatment
of parkinsonism)
Chemistry:
• It is the metabolic precursor of dopamine
Mechanism of action:
In the brain, levodopa is converted to dopamine by
decarboxylation primarily within the presynaptic terminals
of dopaminergic neurons in the stratium (by action of L-
aromatic amino acid decarboxylase). The dopamine
produced is responsible for the therapeutic effectiveness of
the drug in PD; after release, it is either transported back
into dopaminergic terminals by the presynaptic uptake
mechanism or metabolized by the actions of MAO and
catechol-O- methyltransferase (COMT).
Cont....
If levodopa is administered alone, the drug is largely
decarboxylated by enzymes in the peripheral sites so
that little unchanged drug reaches the cerebral
circulation.
•In addition, dopamine release into the
circulation by peripheral coversion of levodopa
produces undesirable effects,
• In practice, levodopa is administered in
combination with a peripherally acting inhibitor of
aromatic L-amino acid decarboxylase, such as
carbidopa,_that do not penetrate into the CNS.
• Inhibition of peripheral decarboxylase markedly
increases the fraction of administered levodopa that
crosses the blood-brain barrier and reduces the
incidence of peripheral side effects.
• The most commonly prescribed form of
carbidopa/levodopa is the 25/100 form, containing
LEVODOPA
Adverse effects:
A) Central :
• Long-trem therapy leads to “Wearing off” phenomenon: each
dose of levodopa improves mobility for 1 to 2 hours, but rigidity and
akinesia return at the end of dosing interval. Increasing the dose and
frequency of administration can improve this situation, but this often
is limited by the development of dyskinesias (excessive and abnormal
involuntary movements). Patients may fluctuate between being “off,”
having no beneficial effects from their medications, and being “on”
but with dyskinesias, a situation called the on/off phenomenon.
• 2) Mental effects Depression, anxiety, agitation, insomnia, delusions,
hallucinations, euphoria
• 3) Dyskinesias (excessive and abnormal involuntary movements) as
chorea and tremor
B) Peripheral:
• Due to formation of dopamine peripherally
• 3. The most common peripheral side effects are anorexia, nausea,
and vomiting (likely due to dopamine’s stimulation of the
chemoreceptor trigger zone in the medulla oblongata).
• 4. Cardiovascular side effects in the form of orthostatic hypotension
and cardiac arrhythmias
Levodopa Drug Interactions

• Pharmacologic doses of pyridoxine (Vitamin B6) enhance the


extracerebral metabolism of levodopa and prevent its therapeutic
effect unleass a peripheral decarboxylase inhibition is also taken.
• Levodopa should not be given to patients taking monoamine oxidase
A inhibitors or within 2 weeks of their discontinuance, because such
a combination can lead to hypertensive crises

Contraindications
1.psychotic patients
2.Angle-closure glaucoma
3.Cardiac disease
4. Peptic ulcer
5. Melanoma
2.Dopamine receptor agonists
Four orally administered dopamine-receptor agonists are available for treatment of PD:
1.Ergot derivatives: as bromocriptine or pergolide
2.Non ergot derivatives as ropinirole

Adverse effects :
Central :Dyskinesias, mental Disturbances

Peripheral:
A)Gastrointestinal Effects: Anorexia and nausea and vomiting

B)Cardiovascular effects:
postural hypotension
Cardiac arrhythmias
peripheral vasospasm (with ergot derivatives)

Contraindications
• Psychotic patiens
• Angle-closure glaucoma
• Cardiac disease
• Peptic ulcer
• Peripheral vacular disease (ergot derivatives).
3.Monoamine oxidase inhibitors

• Two types of monoamine oxidase (MAO) have been distinguished.


• Monoamine oxidase (A) metabolizes norepinephrine and serotonin;
• Monoamine oxidase (B) metabolizes Dopamine
Selegiline:
Mechanism of action :
• Selective inhibitor of monoamine oxidase B (retards the
breakdown of dopamine). Given alone, it has a weak action. It is
therefore used as adjunctive therapy for patients with a declining
response to levodopa.
Side effects :
• May cause insomnia when taken later during the day.
Drug interactions:
• It should not be taken by patients receiving tricyclic
antidepressants, or serotonin reuptake inhibitors because of the
risk of acute toxic interactions.
• The adverse effects of levodopa may be increased by selegiline.
4.Catechol O methyl transferase inhibitors
Tolcapone
Mechanism of action :Inhibit
catechol O methyl transferase
(COMT) which is responsible for
the conversion of dopa into
methyl dopa. Elevated levels of
methyldopa decreases the
response to levodopa,because
methyldopa competes with
levodopa for an active carrier
mechanism that governs its
transport across the blood-brain
barrier.
prolong the action of levodopa
by diminishing its peripheral
metabolism.
These agents may be helpful in
patients receiving levodopa to
reduce dose and decrease
fluctuations in response
Side effects are similar to
levodopa
5.Amantadine
• Amantadine, an antiviral agent.
• Increases dopamine release.
• Acts as an antagonist at muscarinic receptors .
Antagonist at NMDA receptors (N-methyl-D-aspartate) .
Clinical Use
• Amantadine is less potent than levodopa and its effects disappear after only
a few weeks of treatment
Adverse Effects
1)Central nervous system effects
Peripheral edema
Headache
Heart failure
postural hypotension
Urinary retention
2) Gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry
mouth).
Contraindications
• Amantadine should be used with caution in patients with a history of
seizures or heart failure.
Q&A
• Parkinson disease is marked by a lack of which
chemical in the brain?
• A. Serotonin
• B. GABA
• C. Dopamine
• D. Norepinephrine
• E. None of the above
Q&A
2Q) Following dopamine release from
dopaminergic terminals, which one(s) of the
following activities may occur?

A. Reuptake of dopamine into the


presynaptic, dopaminergic terminal
B. Dopamine metabolism by monoamine
oxidase and catechol-o-
methyltransferase (MAO & COMT)
C. Both
D. Neither
Q&A
3Q) Peripheral adverse effects of levodopa,
including nausea,hypotension, and cardiac
arrhythmias, can be diminished by including
which of the following drugs in the therapy?

• A)Amantadine.
• B)Carbidopa.
• C)Pramipexole.
D) Ropinirole
Answers

• 1)C
• 2)C
• 3)B

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