MSK

Question 1

Acetaminophen:
MOA?
**One exceptionally important use??
Describe what happens in toxicity; what is the antidote?

Answer 1

MOA:

• REVERSIBLE inhib COX esp. in CNS
• No anti-inflammatory effects (I think this is why advil works better for my period pains…)

Tx: Feverish kiddos (NOT ASA!!!)

Toxicity: P450 Metabolism–> NAPQI = toxic metabolite–> Liver toxicity–> TREAT W/ N-ACETYLCYSTINE

Question 2

Aspirin: 
MOA? 
Therapeutic use? 
ADRs (4)? 
What happens in toxicity?

Answer 2

MOA:

• IRREVERSIBLE inhib COX1, COX2–> Inhib TXA2, PGs
• ^ Bleeding time w/o affecting PT, PTT

Tx:

• UNDER 300 mg/ day = Inhib platelet agg
• 300-2400 mg/day = antipyretic/ analgesic
• 2400-4000 mg/day = anti-inflammatory

ADRs:

• GI bleed/ ulceration
• TINNITUS
• ARF/ Interstitial nephritis
• Reyes

Toxicity:
Respiratory ALKALOSIS–> Metabolic ACIDOSIS

Question 3

Celecoxib:
MOA + advantage to use?
Therapeutic use?
ADRs/ CI?

Answer 3

MOA:

• REVERSIBLE inhib COX2 (inflam. cells, endothelium)
• SPARES gastric mucosa and platelets

Tx: RA, osteoarthritis

ADR/ CI: ^ risk thrombosis
CI: SULFA ALLERGY

Question 4

List 5 high yield NSAIDS.
What is their common MOA?
What are their therapeutic uses?
What are their ADRs (2)?

Answer 4

Ibuprofen, Naptoxin, Indomethacin, Ketorolac, Diclofenac
MOA: ALL inhibit COX1, COX2–> Inhib PGs
Tx: Antipyretic, analgesic, anti-inflammatory

ADRs:
- GI ulcer
- Interstitial nephritis + renal ischemia
(PGs act at AFFERENT arteriole)

Question 5

INDOMETHACIN does what for little guys in the NICU?

Answer 5

Closes patent PDA!

Question 6

Lefunomide: 
MOA
Therapeutic use? 
ADRs? 
CI?

Answer 6

MOA:
REVERSIBLE inhib dihydroorate dehydrogenase–>
Inhib PYRIMIDINE synthesis–> STOP T CELL prolif.

Tx: RA, psoriatic arthritis

ADRs: Diarrhea, HTN, HEPATOTOXIC
CI: PREGGOS

Question 7

When should you never give your patient NSAIDS?

Answer 7

WHEN THEY PREGGOS.

Question 8

Bisphosphonates:
List the 4 you should know–what is their common ending?
MOA?
ADRs (3)?

Answer 8

Alend, Iband, Rised, Zoled-RONATE

MOA: Pyrophosphate analog
Bind Hypoxyapatate–> STOP OSTEOCLAST ACTIVITY

Tx:

• Osteoporosis, Pagets, Bone mets, OI
• Hypercalcemia

ADRs:

• Corrosive esophagitis
• Jaw osteonecrosis
• Atypical stress fractures

Question 9

Teripartatide:
MOA?
Therapeutic use?
ADRs?

Answer 9

MOA:
Recombinant PTH; admin SQ daily to ^ OSTEOBLAST activity

Tx: Osteoporosis (best at ^ bone growth)

ADRs: Transient HYPERcalcemia

Question 10

What are 4 drugs used to treat gout + their MOAs?

Answer 10

• Allopurinol (inhibits Xanthane oxidase)
• Febuxostat (inhibits Xanthane oxidase)
• *These stop Hypoxanthine–> Xanthane**
• Pegloticase
  (Recomb Uricase: UA–> allantoin = H2O soluble)
• Probenecid (inhibits UA reabsorption in PT of nephron)

Question 11

What are two therapeutic uses for allopurinol?

Answer 11

• Treats gout

- Prevents tumor-lysis asstd. nephropathy

Question 12

How do allopurinol and febuxostat affect 6MP and azathioprine metabolism?

Answer 12

^ 6MP, Azathioprine concentrations bc they are normally metabolized by xanthane oxidase

Question 13

Pegloticase: MOA

Answer 13

Recomb Uricase: UA–> allantoin = H2O soluble

Question 14

Probenecid: MOA
What are two therapeutic uses?
ADR?

Answer 14

Inhibits UA reabsorption in PT of nephron
Treats Gout, INHIBITS PENICILLIN EXCRETION

May cause uric acid calculi

Question 15

What are the three drug classes used to treat ACUTE GOUT?

Answer 15

• NSAIDs (Naproxen, Indomethacin)
• Glucocorticoids
• Colchicine

Question 16

What are the two NSAIDS used to treat ACUTE gout?

Why are salicylates CI?

Answer 16

Naproxen, Indomethacin
Salicylates DECREASE UA clearance, and are therefore CI…

NEVER USE SALICYLATES FOR ACUTE GOUT!!!

Question 17

What is the MOA for Colchicine?
What is it used to treat?
What are its ADRs?

Answer 17

MOA:
STABILIZES Tubulin–> STOP polymerization–> STOP neutron chemotaxis and degranulation
(COLchicine = COLD = FREEZE Tubulin)

Tx: Acute, Px Gout
ADRs:
Serious GI upset; NSAIDS better tolerated for acute flare ups

Question 18

TNF-a Inhibitors:
Therapeutic use relevant to MSK?
ADR/ risk?
What should you always check before starting on a TNF-a inhibitor?

Answer 18

Treats Gout (Px)

• ^ infection risk
• Always do PPD because can cause reactivation of TB

Question 19

Which TNF-a inhibitor can be used to treat IBD?

Which AI disease is it NOT good to treat?

Answer 19

Infliximab (the one that starts with an “I”)

NOT good for psoriasis

Question 20

Etanercept:
MOA?
Therapeutic use?

Answer 20

EtanerCEPT = TNF decoy reCEPTor
(fusion protein receptor for TNFa, IgG,1, FC)

Treats RA, psoriasis, ankylosing spondylitis

Question 21

Inflicimab + Adalimumab:
MOA
Therapeutic Uses?

Answer 21

TNFa monoclonal Ab

Treats IBD, RA, ankylosing spondylitis, psoriasis

Question 22

Rasburicase:
MOA?
Therapeutic use?

Answer 22

Recombinant uricase: UA–> Allantoin–> Pee out

This is used to prevent/ treat tumor lysis syndrome

Question 23

Random: How can you ID tumor lysis syndrome?

Answer 23

Look for patient on chemo with peaked T waves due to release of lots of intracellular K+

Question 24

What are the two recombinant uricase drugs?

Answer 24

• pigloticase

- rasburicase