MSK-rheum drugs Flashcards
name the non-depolarizing neuromuscular blockers
-curiums: atracurium and cisatracurium
D-tubocurarine
-curoniums: pancuronium, rocuronium, vecuronium
what is the difference between atracurium and cisatracurium
atracurium produces toxic metabolite responsible for seizures: avoided with cisatracurium
which are the most potent non-depolarizing NMBs?
pancuronium and vecuronium
how do non-depolarizing NMBs work?
prevent opening of channel, prevents any activation of muscle contraction
how does succinylcholine works as depolarizing NMB?
stimulates opening of receptor channel then prevents closing of it and blocks it, prevents repolarization
how do acetylcholinesterase inhibitors affect succinylcholine?
Phase 1: increases initial muscle contraction via increased Ach
Phase 2: antagonizes/reverses depolarization by increased Ach displacing succinylcholine
-give ACHEIs when some recovery evident to speed it up
what are the following drugs effects on heart due to binding cardiac M receptors:
pancuronium, rocuronium, succinylcholine
pancuronium: moderate stimulation of heart (block M receptor)
rocuronium: slight stimulation of heart
succinylcholine: heart block (stimulate M receptor)
which 3 NMBs stimulate histamine release?
atracurium, tubocurarine, succinylcholine
what are edrophonium, neostigmine, pyridostigmine and what are they used for?
anticholinesterase inhibitors
-reverse effects of NMB by preventing metabolism of Ach
what is given with AchEIs and why?
antimuscarinics to reduce off-target stimulation of muscarinic receptors
glycopyrrolate with stigmines, atropine with edrophonium
what is suggamadex?
reversal agent for steroid-derived non-depolarizing NMBs (-curoniums)
what is the difference b/w suggamadex and AchEIs?
suggamadex can reverseany depth of neuromuscular blockade
which NSAID is not used to treat rheumatoid/psoriatic arthritis and why? what is it used for?
acetaminophen: no anti-inflammatory effects
may be used for OA
which NSAID has the shortest half-life as well as the lowest risk for GI toxicity amongst traditional NSAIDs?
diclofenac
which two NSAIDs have the highest risk for GI toxicity
ibuprofen and naproxen
which two NSAIDs are associated with CV events in high dose regimens?
ibuprofen and diclofenac
which two NSAIDs have long half-lives?
naproxem piroxicam (longest)
which NSAID is particularly CV friendly?
naproxen
how are NSAIDs metabolized and excreted? exception?
hepatic metabolism
renal elimination of very little parental drug
-ketorolac is eliminated 58% unchanged in urine
which NSAIDs are most effective?
trick question: none more effective than the other
what is the general treatment steps in RA?
- methotrexate (maybe with steroid/NSAID)
- hydroxychloroquine if milder case
- lefulnomide, sulfasalazine - biologics if these fail (use w/ or w/o methotrexate)
what is the MOA of methotrexate in RA?
anti-inflammatory:
- DHFR inhibition
- increased adenosine: inhibits lymphocyte proliferation and secretion of IL-1, TNF, IFN
what is the MOA for hydroxychloroquine?
anti-inflammatory:
- increases intracellular vacuole pH
- can’t digest antigens and present to CD4’s
- no activation of CD4 cells
what is the MOA for leflunomide?
inhibits step in de novo pyrimidine synthesis
- causes cell cycle arrest in lymphocytes
- Ig production is suppressed
what is the MOA for sulfasalazine?
metabolized to mesalamine: inhibits PG/LT production = anti-inflammatory
adalimumab
anti-TNF-alpha
certolizumab
anti-TNF-alpha
etanercept
anti-TNF-alpha
golimumab
anti-TNF-alpha
infliximab
anti-TNF-alpha
anakinra: MOA and use
for RA
competitively inhibits IL-1 binding to IL-1R1
tocilizumab: MOA and use
for RA
anti-IL-6-receptor antibody
abatacept: MOA and use
for RA
binds CD80/86 and prevents T cell stimulatory signal from CD28 (fusion of CTLA-4 to Ig Fc fragment)
rituximab: MOA and use
for RA
anti-CD20, induces B cell lysis
apremilast: MOA and use
for psoriatic arthritis
PDE4 inhibitor: improves swelling of arthritis and plaques of psoriasis
colchicine: MOA and uses
for gouty arthritis only: prophylaxis and termination of attacks
binds tubulin, prevents polymerization of tubules
-prevents PMN motility/activity and thus inflammation
indomethacine: use and MOA
relieve acute attack of gouty arthritis
COX-inhibitor
allopurinol: use and MOA
reduce plasma uric acid and urinary excretion of UA
prevent uric acid nephrolithiasis
inhibits xanthine oxidase: xanthine and hypoxanthine are more soluble
febuxostat: use and MOA
lower urate levels in patients who can’t tolerate allopurinol due to renal impairment
potent inhibitor of xanthine oxidase
probenecid: use and MOA
increases uric acid excretion in patients where it’s too low
blocks post-secretory reabsorption by inhibiting organic acid transporter
pegloticase: 2 uses, MOA
- unseemly tophi
- severe gout where other therapy ineffective or contraindicated
- formulation of urate oxidase, which converts UA to much more soluble allantoin
