Glossary of T2 anti-parkinson's and other motor disorder - pharm

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What is the pathophysiology of PD?
loss of dopamine in the nigrostriatal pathway that causes the thalamus to become overstimulated with GABA
What is the first line drug choice in PD?
levodopa (metabolic precursor of dopamine) - can cross the BBB to get in basal ganglia and be converted to dopamine; extremely short half-life (plasma levels drop and cause on-off phenomenon, person gets sudden tremors, etc)
What is the disadvantage of levodopa and how is it remedied?
large doses are required because the drug gets decarboxylated in the periphery to dopamine; remedy situation by using carbidopa (blocks GI and peripheral tissue metabolism of DOPA to dopamine- doesn't get by BBB- doesn't hurt the dopamine in the CNS)
What receptor and pathway are most involved in Parkinson's?
D2; D2 activation inhibits the indirect pathway (causes more GABA to be released from the striatum leading to more GABA release at the thalamus (causing a net inhibition at the thalamus)
How many dopamine receptors are there and what do they each do to cAMP?
D1,2,3,4,5; D1 and D5 cause in increase in cAMP; D2,3,4 cause a decrease in cAMP
What Dopamine receptor do the anti-Parkinson's dopamine agonists largely activate?
Name the four dopamine agonist used in parkinson's treatment
bromocriptine -ergoline-D2; also used for hyperprolactinemia), ropinirole (non-ergoline-D2), pramipexole (non-ergoline-D3),pergolide (ergoline D2,D1) (hint: old parkinson's pts BuRPP)
Name the benefits and limitations to dopamine agonists.
BENEFITS:directly stimulates the dopa receptor, independent of viable dopamine cells, reduces risk of dyskinesia, not affected by dietary proteins(like levadopa), delays motor complications; LIMITS:have to titrate individual dose, s/e:N/dizzy, halluncinations, illusions, somnolence, edema, compulsions
Using what drug with l-dopa (levadopa) will prevent what?
carbidopa + L-dopa will prevent the levadopa from being broken down in the periphery by dopa decarboxylase (carbidopa is an inhibitor of dopa decarboxylase)
What two enzymes can metabolize levadopa into dopamine in the periphery?
COMT and DDC (dopa decarboxylase)
What is the role of MAOb?
break-down dopamine in the presynaptic channel
what is the role of COMT?
break-down dopamine in the periphery
Name all the major categories of drugs that can treat Parkinsons.
precursor of dopamine(levadopa); dopamine agonists (4), MAOb inhibitors, COMT inhibitors, anti-viral(amantadine), antimuscarinics (BTB), apomorphine
Name the 3 anti-muscarinic drugs used in PD treatment.
BTB - benztropine, trihexyphenidyl, biperiden (decrease in dopamine causes an increase in Ach)
Name the COMT inhibitors used in treating parkinson's disease.
entacapone and tolcapone (hepatotoxic) - think of al capone
Name the MAOb inhibitors.
selegiline(metabolized to weak amphetamine) and rasagiline(irreversible blocking)
What would you need to give with apomorphine to prevent a common side-effect?
anti-emetic - acute emesis 5-HT3 antagonist like Tigan
Name the anti-PD drug that is a combo levadopa/carbidopa that is orally dissolvable.
what is an essential tremor?
a neurological disorder characterized by shaking of (usually) the hands, evoked by intential movements; very common; incidence and prevalence increases with age; 95% upper limbs, 34% head, benign condition
how do you treat essential tremor?
pharm - non-selective b-blocker, propanolol and/or anticonvulsant primidone; SURGICAL: DBS(deep brain stimulation), Thalamotomy, gamma knife thalamotomy.
Name the disorder that is characterized by leg dysthesias that are exacerbated by inactivity, relieved by movement?
RLS Restless Leg Syndrome
Name the disorder that is characterized by brief, repetitive jerking of lower limbs while in stage 1 and 2 sleep; causes awakening.
PLMD - Periodic Limb Movement Disorder
Who commonly gets RLS Restless Leg Syndrome?
19% of pregnant women
Restless leg syndrome and Periodic Limb Movement Disorder is exacerbated by what?
caffeine, TCAs, SSRIs, anemia, family history
How do you diagnose Restless leg syndrome and PLMD?
RLS- clinically; PLMD- sleep study
What is the FDA approved med for RLS?
ropinirole (dopamine agonist)

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