MSK, Skin, and Connective Tissue Drugs

Question 1

mechanism of acetaminophen

Answer 1

reversive inhibition of COX1, COX2

Question 2

clinical use of acetaminophen

Answer 2

• antipyretic, analgesic
• NOT anti-inflamm
• use in children instead of aspirin to prevent Reye syndrome

Question 3

toxicity of acetaminophen

Answer 3

• hepatic necrosis - metabolite NAPQI depletes glutathione and forms toxic tissue byproducts in the liver (treat with N-acetylcysteine) –> alcohol induces the enzyme that breaks down acetaminophen, increasing levels of this toxic metabolite
• PUBs (PGs protect gastric mucosa)
• interstitial nephritis, renal ischemia (PGs dilate afferent arterioles)

Question 4

mechanism of aspirin

Answer 4

irreversible inhibitor of COX1, COX2 via acetylation –> decreased synthesis of TXA2 (for the lifetime of the platelet - 10 days) and PGs –> increased bleeding time

Question 5

clinical use of aspirin

Answer 5

• low dose: antiplatelet
• medium dose: antipyretic, analgesic
• high dose: anti-inflamm

Question 6

toxicity of aspirin

Answer 6

PUBs, tinnitus, renal ischemia, interstitial nephritis, Reye syndrome (liver/brain edema), metabolic acidosis/respiratory alkalosis

Question 7

mechanism of celecoxib

Answer 7

reversible inhibition of COX2

Question 8

clinical use of celecoxib

Answer 8

• RA, osteoarthritis

- colon adenocarcinoma

Question 9

toxicity of celecoxib

Answer 9

• sulfa allergy

- thrombosis (TXA2 is NOT inhibited leading to unchecked aggregation)

Question 10

mechanism of bisphosphonates (-dronate)

Answer 10

• pyrophosphate analogues that inhibit osteoclast function by blocking apical GTPase –> inhibit bone resorption
• bridge first 48 hrs with calcitonin

Question 11

clinical use of bisphosphonates (-dronate)

Answer 11

• osteoporosis
• hypercalcemia
• Paget disease of bone

Question 12

toxicity of bisphosphonates (-dronate)

Answer 12

• corrosive esophagitis

- jaw osteonecrosis

Question 13

mechanism of teriparatide

Answer 13

• recombinant PTH analog that increases osteoblast activity when given intermittently

Question 14

clinical use of teriparatide

Answer 14

osteoporosis - causes bone growth

Question 15

toxicity of teriparatide

Answer 15

• transient hypercalcemia

- risk of osteosarcoma if used > 2 yrs

Question 16

vemarafinib

Answer 16

BRAF TKI used for melanoma with BRAF V600E mutation unnameable to surgical resection

Question 17

allopurinol

Answer 17

• xanthine oxidase inhibitor –> decreased conversion of purines to uric acid
• used in gout to prevent uricemia
• used in lymphoma and leukemia to prevent tumor lysis-associated nephropathy
• increases concentrations of azathioprine and 6-MP since XO normally metabolizes these drugs

Question 18

febuxostat

Answer 18

XO inhibitor

Question 19

pegloticase

Answer 19

recombinant uricase that catalyzes metabolism of of uric acid to allantoin which is more water soluble

Question 20

probenecid

Answer 20

inhibits reabsorption of uric acid in PCT –> uricemia is fixed, but can cause uric acid nephrolithiasis

Question 21

colchicine

Answer 21

binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation (used for gout)

Question 22

infliximab, adalimumab

Answer 22

anti-TNFa monoclonal antibody

Question 23

etanercept

Answer 23

fusion of IgG and TNF-a receptor (soluble TNFa receptor!)

Question 24

Before starting any TNFa modulator, it is important to do what?

Answer 24

TB test - inhibiting TNFa function can lead to reactivation of TB since TNFa is important in granuloma formation and stabilization

Question 25

naproxen

Answer 25

like ibuprofen (rev COX1 and 2 inh) but longer t1/2

Question 26

indomethacin

Answer 26

used to close PDA (vs. PGE1 and PGE2 used to keep it OPEN)

Question 27

ketorolac

Answer 27

most efficacious NSAID