FA: Musculoskeletal, Skin, CT Drugs

Question 1

Acetaminophen

Answer 1

MOA: reversibly inhibits cyclooxygenase, mostly in the CNS; inactivated peripherally
Clinical Use: antipyretic, analgesic, but NOT anti-inflammatory; used instead of aspirin to avoid Reye’s syndrome in those under 20 with viral infections
Toxicity: overdose produces hepatic necrosis; acetaminophen metabolite (NAPQ1) depletes glutathione and forms toxic tissue by-products in the liver. N-acetylcysteine is the antidote - it regenerates glutathione

Question 2

Aspirin

Answer 2

MOA: irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) via acetylation, which decreases the synthesis of TXA2 and prostaglandins; increases bleeding time; no effect on PT, PTT; a type of NSAID
Clinical Use: low dose (

Question 3

Celecoxib

Answer 3

MOA: reversibly inhibits specifically the cyclooxgenase (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. Thus, does not have the corrosive effects of other NSAIDs on the GI lining; spares platelet function as TXA2 production is dependent on COX-1
Clinical Use: rheumatoid arthritis, osteoarthritis
Toxicity: increased risk of thrombosis; sulfa allergy

Question 4

NSAIDs: Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac

Answer 4

MOA: reversibly inhibit cyclooxygenase (both COX-1 and COX-2); block prostaglandin synthesis
Clinical Use: antipyretic, analgesic, anti-inflammatory; indomethacin is used to close a PDA
Toxicity: interstitial nephritis, gastric ulcer (prostaglandins protect the gastric mucosa); renal ischemia (prostaglandins vasodilate the afferent arteriole)

Question 5

Bisphosphonates: Alendronate (-dronate)

Answer 5

MOA: pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity
Clinical Use: osteoporosis, hypercalcemia, Paget disease of bone
Toxicity: corrosive esophagitis (patients are advised to take with water and remain upright for 30 min); osteonecrosis of the jaw

Question 6

Teriparatide

Answer 6

MOA: recombinant PTH analog given subcutaneously daily; increases osteoblast activity
Clinical Use: osteoporosis; causes increased bone growth compared to anti-resorptive therapies (bisphosphonates)
Toxicity: transient hypercalcemia; may increase risk of osteosarcoma (seen in rodent studies)

Question 7

Drugs for Gout

Answer 7

Allopurinol, febuxostat, pegloticase, probenecid

Question 8

Allopurinol

Answer 8

Inhibits xanthine oxidase after being converted to alloxanthine; decreases conversion of xanthine to uric acid; also used in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy; increases concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase)

Question 9

Febuxostat

Answer 9

Inhibits xanthine oxidase

Question 10

Pegloticase:

Answer 10

Recombinant uricase that catalyzes metabolism of uric acid to allantoin (a more water-soluble product)

Question 11

Probenecid

Answer 11

Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin); can precipitate uric acid calculi

Question 12

Acute Gout Drugs

Answer 12

NSAIDs, glucocorticoids (oral or intra-articular), colchicine
Do NOT give salicylates; all but the highest doses depress uric acid clearance; even high doses (5-6 g/day) have only minor uricosuric activity

Question 13

Colchicine

Answer 13

Binds and stabilizes tubulin to inhibit microtubule polmerization, impairing neutrophil chemotaxis and degranulation
Acute and prophylactic value
GI side effects

Question 14

TNF-a Inhibitors

Answer 14

Etanercept, Infliximab, Adalimumab

Question 15

Etanercept

Answer 15

Fusion protein (receptor for TNFa + IgG1Fc) produced by recombinant DNA (EtanerCEPT is a TNF decoy reCEPTor)
Clinical use: rheumatoid arthritis, psoriasis, ankylosing spondylitis

Question 16

Infliximab & Adalimumab

Answer 16

Anti-TNF-a monoclonal antibody

Clinical use: IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis