From Jen: MSK/CT

Question 1

ASA

Answer 1

MOA: irreversibly inhibit COX by covalent binding, which ↓ synthesis of both TXA and PGE

Low dose: ↓ platelet aggregation
Mid dose: antipyretic, analgesic
High dose: anti-inflammatory

Toxicity: GI upset
Chronic use: acute renal failure, interstitial nephritis, and upper GI bleeding
Reye syndrome in kids with viral illness*

Question 2

NSAIDs

Answer 2

Ibuprofen, naproxen, indomethacin, ketorolac

Reversibly inhibit COX1/2. Block PGE synthesis

Use: antipyretic, analgesic, anti-inflammatory
Indomethacin: used to close PDA

Toxicity: renal damage, aplastic anemia, GI distress, ulcers

Question 3

COX-2 Inhibitors

Answer 3

Celecoxib

MOA: reversibly inhibit COX-2 only, which is found in vascular endothelium and inflammatory cells and mediates inflammation and pain

Spares COX-1, which helps maintain gastric mucosa

Uses: RA and osteoarthritis

Toxicity: ↑ risk of thrombosis, sulfa allergy, less toxicity to GI mucosa

Question 4

Acetaminophen

Answer 4

Reversibly inhibits COX, mostly in CNS, inactivated peripherally

Use: antipyretic, analgesic, but lacking in anti-inflammatory properties. Use instead of ASA in kids (prevent Reye)

Toxicity: OD- hepatic necrosis
Metabolite depletes glutathione and forms toxic tissue effects in liver

Antidote: N-acetylcysteine (regenerates glutathione)

Question 5

Bisphosphonates

Answer 5

Etidronate, pamidronate, alendronate, risedronate

MOA: inhibit osteoclastic activity: reduce both formation and resorption of hydroxyapatite

Use: malignancy-associated hypercalcemia, Paget’s disease, menopausal osteoporosis

Toxicity: corrosive esophagitis, nausea, diarrhea

Question 6

Colchicine

Answer 6

MOA: inhibits microtubule polymerization, impairing leukocyte chemotaxis and degranulation

Use: acute gout

Toxicity: GI side effects

Question 7

Probenecid

Answer 7

MOA: inhibits reabsorption of uric acid in PCT (also increased secretion of PCN)

Use: chronic gout

Question 8

Allopurinol

Answer 8

MOA: inhibits xanthine oxidase, ↓ conversion of xanthine to uric acid.

Use: chronic gout
Also used in lymphoma and leukemia to prevent tumor lysis associate urate nephropathy

***↑ concentration of both azothioprine and 6-percaptopurine

Question 9

Etanercept

Answer 9

MOA: recombinant form of human TNF receptor that binds TNF

Use: RA, psoriasis, ankylosing spondylitis

Question 10

Infliximab

Answer 10

Anti-TNF Ab

Use: Crohn’s disease, RA, ankylosing spondylitis

Toxicity: predisposes to infection (esp. reactivation of latent TB)