Musculoskeletal, Skin, and CT

Question 1

Aspirin (acetylsalicylic acid) / ASA

Answer 1

Irreversible inhibitor of cyclooxygenase (COX1 AND COX2) via covalent acetylation
Decreases synthesis of both thromboxane A2 (TXA2) and prostaglandins
Type of NSAID

Question 2

How does aspirin irreversibly inhibit COX 1 and 2?

Answer 2

Covalent acetylation

Question 3

How does aspirin affect bleeding time, PT, and PTT?

Answer 3

Increased bleeding time until new platelets are produced (7 days)
No effect on PT, PTT

Question 4

Clinical use for low, intermediate, and high doses of aspirin

Answer 4

Low dose (

Question 5

Aspirin toxicity

Answer 5

Gastric ulceration
Tinnitus (CN VIII)
Chronic use can lead to acute RENAL failure, interstitial nephritis, and upper GI bleeding
Risk of Reye syndrome in children treated for viral infection
Stimulates respiratory centers = hyperventilation and respiratory alkalosis

Question 6

What syndrome can children get if given aspirin? What is one case in which you should give aspirin to children?

Answer 6

Reye syndrome (fulminant hepatic necrosis and encephalopathy)

Kawasaki syndrome (IVIG and aspirin)

Question 7

NSAIDs

Answer 7

Ibuprofen
Naproxen
Indomethacin
Ketorolac
Diclofenac

Question 8

Ibuprofen, Naproxen, Indomethacin, Ketorolac, Diclofenac
Mechanism?
Uses?

Answer 8

Reversibly inhibit COX1 and COX2 = block prostaglandin synthesis
Uses = antipyretic, analgesic, anti-inflammatory
Indomethacin used to close a PDA

Question 9

NSAIDs

Toxicity?

Answer 9

Interstitial NEPHRITIS
Gastric ulcer (PGs protect gastric mucosa)
Renal ischemia (PGs vasodilate afferent arteriole)

Question 10

Which NSAID can be used to close a PDA?

Answer 10

Indomethacin

Prostaglandin E2 used to keep open

Question 11

COX2 inhibitor

Mechanism?

Answer 11

Celecoxib
Reversibly inhibit specifically COX 2 isoform = found in inflammatory cells and vascular endothelium; mediates inflammation and pain
Spares COX 1 = helps maintain gastric mucosa

Benefit = does not have corrosive effects of other NSAIDs on the GI lining; spares platelet function as TXA2 production is dependent on COX1

Question 12

Celecoxib
Uses?
Toxicity?

Answer 12

Selective COX2 inhibitor
Uses = rheumatoid arthritis and osteoarthritis; patients with gastritis or ulcers
Toxicity = increased risk of thrombosis; sulfa allergy

Question 13

Acetaminophen / APAP
Mechanism?
Uses?

Answer 13

Reversibly inhibits COX, mostly in CNS
Inactivated peripherally

Antipyretic, analgesic, NOT anti-inflammatory
Used instead of ASA to avoid Reye syndrome in children with viral infection

Question 14

Does acetaminophen have anti-inflammatory effects?

Answer 14

NO

Question 15

Acetaminophen toxicity?

Answer 15

LIVER
Overdose = hepatic necrosis
Acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver

Antidote = N-acetylcysteine (regenerates glutathione)

Question 16

Antidote for acetaminophen overdose?

Answer 16

N-acetylcysteine

Regenerates glutathione

Question 17

Bisphosphonates

Mechansim?

Answer 17

Alendronate
“-dronate”
Pyrophosphate analogs
Bind hydroxyapatite in bone, inhibiting osteoclast activity

Question 18

Alendronate
Uses?
Toxicity?

Answer 18

Bisphosphonate
Uses = osteoporosis, hypercalcemia, Paget disease of bone
Toxicity = corrosive esophagitis (take with water and remain upright for 30 min); osteonecrosis of jaw

Question 19

Chronic gout drugs (preventive)

3; “AFP”

Answer 19

Allopurinol
Febuxostat
Probenecid

Question 20

Allopurinol - gout prevention
Mechanism?
Uses?

Answer 20

Xanthine oxidase inhibitor
Decreases conversion of xanthine to uric acid
Used in lymphoma/leukemia to prevent tumor lysis-associated urate nephropathy
Increases concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase)

Question 21

Should salicylates be used in the long term/preventative treatment of gout?

Answer 21

NO = all but highest doses depress uric acid clearance

Even high doses (5-6g/day) have only minor uricosuric activity

Question 22

Febuxostat

Answer 22

Gout prevention

Inhibits xanthine oxidase

Question 23

Probenecid

Answer 23

Gout prevention
Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin)

High dose salicylates have similar effect but only MINOR (don’t use for prevention)

Question 24

Acute gout drugs (3)

Answer 24

NSAIDs = naproxen, indomethacin
Glucocorticoids = oral or intraarticular
Colchicine

Question 25

Colchicine
Mechanism?
Side effects?

Answer 25

Binds and stabilizes tubulin to inhibit microtubules polymerization = impairs leukocyte chemotaxis and degranulation
Acute and prophylactic value
GI side effects

Question 26

Which gout drug has both acute and prophylactic value?

Answer 26

Colchicine

Binds and stabilizes tubulin to inhibit microtubules polymerization = impairs leukocyte chemotaxis and degranulation

Question 27

List the breakdown pathway from purines to uric acid

Answer 27

Diet/nucleic acids –> purines –> hypoxanthine –[XO]–> xanthine –[XO]–> plasma uric acid

Uric acid then either excreted in urine or deposited as urate crystals in joints (gout)

Question 28

TNF-a inhibitors (3; “AEI”)

Answer 28

Etanercept
Inflixamab
Adalimumab

All predispose to infection, including reactivation of latent TB = TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes

Question 29

How do TNF-a inhibitors predispose to infection? What type of infection is commonly reactivated?

Answer 29

TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes

Reactivation of latent TB can be seen

Question 30

Etanercept
Mechanism?
Uses?

Answer 30

Fusion protein (receptor for TNF-a + IgG1 Fc) = produced by recombinant DNA
"EtanerCEPT is a TNF decoy reCEPTor"

Uses = RA, psoriasis, ankylosing spondylitis

Question 31

Infliximab, Adalimumab
Mechanism?
Uses?

Answer 31

Anti-TNF-a monoclonal antibody

Uses = IBD, RA, ankylosing spondylitis, psoriasis