Parkinsons Flashcards
What are the six cardinal signs of Parkinson’s Disease?
Feathered and tarred - TAR FLUFF (TAR FLF)
Tremors
Akinesia
Rigidity
Flexed-neck posture
Loss of postural reflexes
Freezing phenomenon
Why do we need to give the DA precursor L-DOPA rather than just dopamine?
Dopamine can’t cross the BBB.
Degeneration is what structure is responsible for Parkinsons?
The substantia nigra
What is the name of the projection from the substantia nigra to the basal ganglia?
The nigrostriatal pathway.
What structure does this DA/ACh balance actually effect directly?
The striatum (the receiving end of the nigrostriatal pathway).
What’s the pharmacokinetic con of levodopa?
Very low bioavailability due to MAOa (1-5%)
What enzyme catalyses the conversion of levodopa to dopamine?
DOPA decarboxylase.
What is given to deal with the piss poor bioavailability of levodopa?
Hint: it also ends in -dopa.
Hint: automobile auction.
CARBIDOPA. It’s a DOPA decarboxylase inhibitor that decreases peripheral metabolism of L-dopa so more can reach the brain.
What does carbidopa inhibit?
DOPA decarboxylase.
What’s the THM for levodopa efficacy?
It doesn’t treat the underlying disease (but does increase life expectancy). The responsiveness to L-DOPA therapy over time decreases, but we’re not sure if that’s due to disease deterioration or something like receptor downregulation.
Why do patients love carbidopa?
Reduces the prevalence and severity of initial side effects since less dosing is necessary.
Bonus: Carbidopa allows for about a 75% dose reduction of levodopa.
Levodopa has a pretty short duration of action. What are two characteristic side effects of levodopa?
DYSKINESIA - possibly a consequence of fluctuations in plasma concentration.
The ON-OFF phenomenon - cycle of exacerbation and resolution of symptoms.
What unwanted effects of levodopa will the patient have to deal with initially? (Less important for the subject than dyskinesia and on-off cycles).
THINNING-ish symptoms - anorexia, vomiting, nausea.
PSYCHOLOGICAL DISTURBANCES.
Carbidopa increases availability to the brain from X to Y.
1-5% to about 90%.
What are the non-ergot derived DA receptor agonists? Which DA receptors do they target?
PrimapeX lol
How would you help an imprisoned primapeX absail out of prison?
Pramipexol
Ropinirol (smuggle a rope in a roll)
D2 and D3
What are the non-ergot derived DA receptor agonists?
Pramipexol
Ropinirol
D2 and D3.
What are the ergot-derived DA receptor agonists?
Zac was so annoyed that he was lied to about the pronunciation of “purge” that he went and blew his straight friend in a crypt somewhere.
What DA receptors do they target? (Ergo, Neo, you are the One).
Bromocriptine and pergolide
D1 and D2.
What are the ergot-derived DA receptor agonists?
What DA receptors do they target?
Bromocriptine and pergolide.
D1 and D2.
Why are non-ergot derived compounds a common first-line treatment over levodopa?
Equieffective but better tolerated, NO FLUCTUATIONS
What are the pramipexol and ropinirol side effects?
(he’s called primapeX because he loves sex drugs and rock n’ roll… and gambling).
He needed to get out of jail because he was so bored he was seeing things.
Somnolence
Compulsivity
Hallucinations
Older, ergot-derived DA receptor agonists had BAD side effects (pulmonary fibrosis, cardiac valve fibrosis). Why would they have given them anyway in addition to levodopa?
To even out the fluctuations in DA plasma concentration and avoid that dyskinesia and on/off cycling.
What is bromocriptine and pergolide’s big side effect?
Pulmonary fibrosis
Heart valve fibrosis.
Side effects:
Entacapone:
Selegiline:
diarrhoea
amphetamine as a breakdown product.
Which breakdown inhibitor is like Selegiline but without the amphetamine products?
Rasagiline
Amanditine: Parkinsons and Antiflu. Much shitter version of levodopa (milder side effects) but ANTIMUSCARINIC
Amantadine side effects: antimuscarinic.
What actually are entecapone, selegiline and rasagiline?
DA breakdown inhibitors.
Entecapone inhibits ______ and the gilines inhibit _____
COMT and MOAb
The anticholinergics are benztropin, benzhexol, biperiden
benztropin, benzhexol and biperiden are anticholinergics.
