Neuropharm 2: Treatment of Parkinson's disease Flashcards
Parkinson’s Disease
Define parkinson’s Disease
loss of 70-80% of dopamine containing neurons in substantia nigra
Parkinson’s Disease
what are symptoms of Parkinson’s Disease
- bradykinesia (impairment of voluntary motor control and slow movements or freezing)
- resting tremor
- msucular rigidity
Parkinson’s Disease
how can parkinson’s disease be treated and give 3 examples of how it can be done
think dopamine and increase, decrease and other agonists and what they can do
- based on replacement of dopamine
- done by:
-increase dopamine synthesis
-reduced dopamine breakdown
-other agonists that can act at dopamine receptors
Parkinson’s Disease: Levodopa Alone
what happens if Levodopa is given alone as a drug?
majority is metabolised before it reaches the brain
Parkinson’s Disease: increased synthesis
IN the PNS, what 2 drugs can be given to reduce conversion of dopamine to Noradrenaline and how does it do this
for first part think carbs and think Beserk
think enzymes for second part
- carbidopa or beserazide
- inhibits DOPA decarboxylase
Parkinson’s Disease:Increased synthesis
what enzymes break down DOPA in the CNS
- COMT
- MAO-B
Parkinson’s Disease:Increased synthesis
what drugs can inhibit COMT
think Al capone
- entacapone
- tolcapone
Parkinson’s Disease:Increased synthesis
what drugs can inhibit MAO-B
think words that rhyme with bean
- selegiline
- rasagiline
Parkinson’s Disease: Increased synthesis
what are L-DOPA actions and what is the drawback
think symptoms of Parkinsons for actions
for drawback think about volatility of drug
- improvement in:
tremor
rigidity
bradykinesia - drawback: can fluctuate dramatically and wears off in hours
Parkinson’s Disease:Increased synthesis (pharmacokinetics)
what are ways to improve the drawback of L-DOPA
think formulations that include different types of beads, and think gel in gastrointestinal tract
- improve formulations to allow sustained release via tablets that incorporate both immediate and extended release beads
- use intestinal gel administered to jejunum via a gastrostomy tube
no.2
Parkinson’s Disease:Increased synthesis
what are adverse effects of L-DOPA and how can one of them be treated
think being sick, and for the thing that treats it, blood pressure and the term for involuntary movement
- Nausea and anorexia - treated using domperidone
- hypotension
- Dyskinesia (involuntary movements)
Parkinson’s Disease:Increased synthesis
what is the problem with producing too much dopamine and how can this be treated
think about scary people in the corner of your bedroom, being discumbobulated for first part
for second part think about antipsychotics
- patient can get hallucinations, psychosis and confusion
- treated using non-dopaminergic antipsychotics
Parkinson’s Disease: Inhibit breakdown
when are MAO-B inhibtors effective?
in early stage Parkinson’s
Parkinson’s Disease: Inhibit breakdown
why are there less adverse effects when you use MAO-B inhibitors to inhibitor dopamine breakdown than when you use LOPA to increase synthesis?
think about WHERE MAO-B is found and what type of adverse effects are caused by LOPA
MAO-B is only found in the brain in glial cells, so you can’t get all the peripheral side effects
Parkinson’s Disease: Inhibit breakdown
what is the drawback of selegiline and how can this be overcome?
think types of administration and what this causes and think what type of molecule deravatives selegiline metabolites are what what this leads to
- if orally administered, first-pass metabolism will occur.
- metabolites are l-amphetamine derivatives so this can lead to anxiety and insomnia
- transdermal administration is better
