Drugs For Parkinson Diseases Flashcards
The hallmark of parkinson’s disease is …..
Loss of dopaminergic neuron and presence of lewy bodies in the pars compacta of the substantia nigra of the brain
Cardinal signs of parkinsonism disease are
Muscular rigidity
Bradykinesia ( Decreased movt)
Postural imbalance
Resting tremor
The anti-psychotics and ati-emetics are dopamine receptor antagonist which can result in parkinsonism diseases like effect examples are…..
Antipsychotic
Haloperidol
Thorazine
Anti emetics
Metoclopramide
Prochlorperazine
The rate limiting step in the synthesis of dopamine is ……..
Conversion of tyrosine to L DOPA
by tyrosine hydroxylase
Dopamine can be metabolised by which enzymes
Aldehyde dehydrogenase
COMT
MOA
The products of dopamine metabolism are
COMT 3MT
MAO 3,4 Ddihydroxyphenylacetic acid
ADD Homovallinic acid
The products of dopamine metabolism are
COMT 3MT
MAO 3,4 Ddihydroxyphenylacetic acid
ADD Homovallinic acid
The principles of drugs for treating parkinsonism disease are
Increase the concentration of dopamine
Work at the receptor
What is the single most important agent in the treatment of dopamine
Levodopa L-DOPA
Levodopa is administered………
Orally
Why is levodopa best administered on an empty stomach
Because its absorption is limited by the rate and extent of gastric emptying.
Hence delayed by gastric emptying
Dopamine is absorbed in what part of the intestine
Small intestine
L DOPA is transported across the intestine and circle of Willis by ……
Aromatic amino acid transporter
Why is CARBIDOPA administered with L DOPA
CARBIDOPA is a L DOPA decarboxylase inhibitor which prevents the action of L DOPA peripherally
CARBIDOPA cannot cross the BBB T/F
True
The half life of L DOPA is ……….
6-8 hours
Side effects of levodopa are
Dyskinesia
On and off effect
Hallucinations
Vomiting that can be prevented by CARBIDOPA
Confusion
Dopamine receptor agonist used for the treatment of parkinsonism disease is divided into classes ……….. and ………..
Ergot classes
Non ergot classes
The ergot derivatives used in the treatment of parkinsonism are
Bromocriptine
Carbegoline
Pergolide
The non ergot dopaminergic receptor agonist are
Ropinirole
Pramipexole
Ergot derivatives of DA receptor agonist undergo extensive first pass effect with ………….. %of bioavailability
50%
The half lifes of ergot derivatives DA receptor agonist are
Pergolide 27 hours
Bromocriptine 12-14 hours
The non ergot derivatives DA receptor agonist are metabolised in ………
Liver and excreted through bile and a little unchanged excreted through urine
The two non ergot derivatives DA agonist are newer drugs, administered orally with ……… %of bioavailability
50-90%
Average half life of ergot derivatives DA receptor agonist are
8-24 hrs
Bromocriptine and carbegoline elicit their strong agonist effect on …….
D2 Receptors
The side effects associated with ergot derivatives DA receptor agonist occurs through…….
Adrenergic and serotonin receptors
Pergolide has affinity for both D1 and D2 but stronger at …..
D1
Non ergot derivatives DA receptor agonists have activity on D1 D2 D3 which is the lowest and highest
Lowest at D1
Maximum at D2 and D3
The peculiarity of on-off phenomenon to dopamine receptor agonist and levodopa is
Levodopa can result in on and off
DA agonist can be used to treat on and off phenomenon
A side effect peculiar to pergolide is ……
Cardiac valvular disease
Side effects associated with dopamine receptor agonists are
Nausea
Vomiting
Hypotension
Fatigue
A side effect associated with newer non ergot derivatives dopamine receptor agonist is
Somnolence
Bromocriptine inhibit the release of glutamate from glutamatergic neuron T/F
True
COMT inhibitors in clinical use are
Entacapone
Tolcapone
How does COMT affect the metabolism of levodopa
It is recruited by CARBIDOPA
It results in metabolism of L DOPA preventing its decarboxylation to Dopamine
Differences between entacapone and tolcapone
Entacapone
Bioavailability is 35%
Crosses BBB less
Less hepatotoxic
2hrs half life
Tolcapone
Crosses BBB more
65% Bioavailability
More hepatotoxic
Longer half life
Side effects of COMT inhibitors include
Nausea Vomiting Hypotension, confusion and Hallucinations somnolence
Hepatotoxicity
Diarrhoea
Dry mouth
Abdominal pain
Back pain
Discolouration of urine
Which MAO enzyme is found centrally
MAO B
The selective inhibition of which MOA is preffered in the treatment of PD
MAO B
At what dose does selegiline act selectively on on MAOB
20mg/day
Other drugs used in the treatment of parkinsonism disease are
Anti muscarinic agent
Artane (trihexyphenidyl)
Benztropine mesylate
Diphenyhydramine
Antiviral drug
Amantadine
