MSK-rheum drugs

Question 1

name the non-depolarizing neuromuscular blockers

Answer 1

-curiums: atracurium and cisatracurium
D-tubocurarine
-curoniums: pancuronium, rocuronium, vecuronium

Question 2

what is the difference between atracurium and cisatracurium

Answer 2

atracurium produces toxic metabolite responsible for seizures: avoided with cisatracurium

Question 3

which are the most potent non-depolarizing NMBs?

Answer 3

pancuronium and vecuronium

Question 4

how do non-depolarizing NMBs work?

Answer 4

prevent opening of channel, prevents any activation of muscle contraction

Question 5

how does succinylcholine works as depolarizing NMB?

Answer 5

stimulates opening of receptor channel then prevents closing of it and blocks it, prevents repolarization

Question 6

how do acetylcholinesterase inhibitors affect succinylcholine?

Answer 6

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

Question 7

what are the following drugs effects on heart due to binding cardiac M receptors:
pancuronium, rocuronium, succinylcholine

Answer 7

pancuronium: moderate stimulation of heart (block M receptor)
rocuronium: slight stimulation of heart
succinylcholine: heart block (stimulate M receptor)

Question 8

which 3 NMBs stimulate histamine release?

Answer 8

atracurium, tubocurarine, succinylcholine

Question 9

what are edrophonium, neostigmine, pyridostigmine and what are they used for?

Answer 9

anticholinesterase inhibitors

-reverse effects of NMB by preventing metabolism of Ach

Question 10

what is given with AchEIs and why?

Answer 10

antimuscarinics to reduce off-target stimulation of muscarinic receptors
glycopyrrolate with stigmines, atropine with edrophonium

Question 11

what is suggamadex?

Answer 11

reversal agent for steroid-derived non-depolarizing NMBs (-curoniums)

Question 12

what is the difference b/w suggamadex and AchEIs?

Answer 12

suggamadex can reverseany depth of neuromuscular blockade

Question 13

which NSAID is not used to treat rheumatoid/psoriatic arthritis and why? what is it used for?

Answer 13

acetaminophen: no anti-inflammatory effects

may be used for OA

Question 14

which NSAID has the shortest half-life as well as the lowest risk for GI toxicity amongst traditional NSAIDs?

Answer 14

diclofenac

Question 15

which two NSAIDs have the highest risk for GI toxicity

Answer 15

ibuprofen and naproxen

Question 16

which two NSAIDs are associated with CV events in high dose regimens?

Answer 16

ibuprofen and diclofenac

Question 17

which two NSAIDs have long half-lives?

Answer 17

naproxem
piroxicam (longest)

Question 18

which NSAID is particularly CV friendly?

Answer 18

naproxen

Question 19

how are NSAIDs metabolized and excreted? exception?

Answer 19

hepatic metabolism
renal elimination of very little parental drug
-ketorolac is eliminated 58% unchanged in urine

Question 20

which NSAIDs are most effective?

Answer 20

trick question: none more effective than the other

Question 21

what is the general treatment steps in RA?

Answer 21

1. methotrexate (maybe with steroid/NSAID)
2. hydroxychloroquine if milder case
   - lefulnomide, sulfasalazine
3. biologics if these fail (use w/ or w/o methotrexate)

Question 22

what is the MOA of methotrexate in RA?

Answer 22

anti-inflammatory:

• DHFR inhibition
• increased adenosine: inhibits lymphocyte proliferation and secretion of IL-1, TNF, IFN

Question 23

what is the MOA for hydroxychloroquine?

Answer 23

anti-inflammatory:

• increases intracellular vacuole pH
• can’t digest antigens and present to CD4’s
• no activation of CD4 cells

Question 24

what is the MOA for leflunomide?

Answer 24

inhibits step in de novo pyrimidine synthesis

• causes cell cycle arrest in lymphocytes
• Ig production is suppressed

Question 25

what is the MOA for sulfasalazine?

Answer 25

metabolized to mesalamine: inhibits PG/LT production = anti-inflammatory

Question 26

adalimumab

Answer 26

anti-TNF-alpha

Question 27

certolizumab

Answer 27

anti-TNF-alpha

Question 28

etanercept

Answer 28

anti-TNF-alpha

Question 29

golimumab

Answer 29

anti-TNF-alpha

Question 30

infliximab

Answer 30

anti-TNF-alpha

Question 31

anakinra: MOA and use

Answer 31

for RA

competitively inhibits IL-1 binding to IL-1R1

Question 32

tocilizumab: MOA and use

Answer 32

for RA

anti-IL-6-receptor antibody

Question 33

abatacept: MOA and use

Answer 33

for RA

binds CD80/86 and prevents T cell stimulatory signal from CD28 (fusion of CTLA-4 to Ig Fc fragment)

Question 34

rituximab: MOA and use

Answer 34

for RA

anti-CD20, induces B cell lysis

Question 35

apremilast: MOA and use

Answer 35

for psoriatic arthritis

PDE4 inhibitor: improves swelling of arthritis and plaques of psoriasis

Question 36

colchicine: MOA and uses

Answer 36

for gouty arthritis only: prophylaxis and termination of attacks
binds tubulin, prevents polymerization of tubules
-prevents PMN motility/activity and thus inflammation

Question 37

indomethacine: use and MOA

Answer 37

relieve acute attack of gouty arthritis

COX-inhibitor

Question 38

allopurinol: use and MOA

Answer 38

reduce plasma uric acid and urinary excretion of UA
prevent uric acid nephrolithiasis
inhibits xanthine oxidase: xanthine and hypoxanthine are more soluble

Question 39

febuxostat: use and MOA

Answer 39

lower urate levels in patients who can’t tolerate allopurinol due to renal impairment
potent inhibitor of xanthine oxidase

Question 40

probenecid: use and MOA

Answer 40

increases uric acid excretion in patients where it’s too low

blocks post-secretory reabsorption by inhibiting organic acid transporter

Question 41

pegloticase: 2 uses, MOA

Answer 41

1. unseemly tophi
2. severe gout where other therapy ineffective or contraindicated
   - formulation of urate oxidase, which converts UA to much more soluble allantoin