FA Musculoskeletal, Skin, and Connective Tissue

Question 1

Aspirin Mechanism

Answer 1

Irreversibly inhibits COX-1 and COX-2 by covalent acetylation, which ↓ production of TXA2 and prostaglandins

Question 2

Aspirin Use

Answer 2

Low dose (<300mg/day): ↓ platelet aggregation
Intermediate dose: (300-2400mg/day): antipyretic and analgesic
High dose (2400-4000mg/day): anti-inflammatory

Question 3

Aspirin Toxicity

Answer 3

Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, upper GI bleeding. Risk of Reye syndrome in children with viral infection. Stimulates respiratory centers, causing hyperventilation and respiratory alkalosis.

Question 4

NSAIDs

Answer 4

Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac

Question 5

NSAID Mechanism

Answer 5

Reversibly inhibit COX-1 and COX-2, blocking PG synthesis.

Question 6

NSAID Use

Answer 6

Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close PDA.

Question 7

NSAID Toxicity

Answer 7

Interstitial nephritis, gastric ulcer (PGs protect gastric mucosa), renal ischemia (PGs vasodilate afferent arteriole).

Question 8

COX-2 inhibitor

Answer 8

celecoxib

Question 9

COX-2 inhibitor (celecoxib) Mechanism

Answer 9

Reversibly inhibit COX isoform 2, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain. Spares COX-1, which helps maintain gastric mucosa (should not have corrosive effects of other NSAIDs). Spares platelet function (TXA2 production is COX-1 dependent).

Question 10

COX-2 inhibitor (celecoxib) Use

Answer 10

Rheumatoid arthritis, osteoarthritis; patients with gastritis or ulcers.

Question 11

COX-2 inhibitor (celecoxib) Toxicity

Answer 11

↑ risk of thrombosis. Sulfa allergy.

Question 12

Acetaminophen Mechanism

Answer 12

Reversibly inhibits COX, mostly in CNS. Inactivated peripherally.

Question 13

Acetaminophen Use

Answer 13

Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome in children with viral infection.

Question 14

Acetaminophen Toxicity

Answer 14

Overdose produces hepatic necrosis; metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote – regenerates glutathione.

Question 15

Chronic gout drugs

Answer 15

Allopurinol, febuxostat, probenecid

Question 16

Allopurinol Mechanism

Answer 16

Inhibits xanthine oxidase, ↓ conversion of xanthine to uric acid.

Question 17

Allopurinol Use

Answer 17

Chronic gout (prevention). Also used in lymphoma/leukemia to prevent tumor lysis associated urate nephropathy.

Question 18

Allopurinol Toxicity

Answer 18

↑ concentrations of azathioprine and 6-MP (both metabolized by xanthine oxidase). Do not give salicylates; all but the highest doses depress uric acid clearance. Even high doses (5-6g/day) have only minor uricosuric activity.

Question 19

Febuxostat Mechanism

Answer 19

Inhibits xanthine oxidase.

Question 20

Probenecid Mechanism

Answer 20

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

Question 21

Acute gout drugs

Answer 21

NSAIDS (indomethacin, naproxen), glucocorticoids (oral or intraarticular), colchicine.

Question 22

Colchicine Mechanism

Answer 22

Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing leukocyte chemotaxis and degranulation.

Question 23

Colchicine Use

Answer 23

Gout - acute and prophylactic value

Question 24

Colchicine Toxicity

Answer 24

GI side effects

Question 25

TNF-α inhibitors

Answer 25

Etanercept, infliximab, adalimumab

Question 26

TNF-α inhibitor toxicity

Answer 26

All TNF-α inhibitors predispose to infection, including reactivation of latent TB, since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes.

Question 27

Etanercept Mechanism

Answer 27

Fusion protein (receptor for TNF-α + IgG1 Fc), produced by recombinant DNA. Etanercept is a TNF decoy receptor.

Question 28

Etanercept Use

Answer 28

Rheumatoid arthritis, psoriasis, ankylosing spondylitis

Question 29

Infliximab Mechanism

Answer 29

Anti-TNF-α monoclonal antibody

Question 30

Adalimumab Mechanism

Answer 30

Anti-TNF-α monoclonal antibody

Question 31

Infliximab Use

Answer 31

IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 32

Adalimumab Use

Answer 32

IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 33

Bisphosphonates

Answer 33

Alendronate, other -dronates

Question 34

Bisphosphonate Mechanism

Answer 34

Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity

Question 35

Bisphosphonate Use

Answer 35

Osteoporosis, hypercalcemia, Paget disease of bone

Question 36

Bisphosphonate Toxicity

Answer 36

Corrosive esophagitis (patients advised to take with water and remain upright for 30 minutes), esophageal cancer, osteonecrosis of the jaw