Musculoskeletal, Skin, and Connective Tissue Pharmacology

Question 1

Mechanism of action of bisphosphonates

Answer 1

Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity

Question 2

Bisphosphonates are used to treat…

Answer 2

1. Osteoporosis
2. Hypercalcemia
3. Paget disease of bone

Question 3

Two toxicities associated with bisphosphonate use

Answer 3

1. Corrosive esophagitis (pts are advised to take with water and remain upright for 30 min)
2. Osteonecrosis of jaw

Question 4

Alendronate and other -dronates are examples of…

Answer 4

Bisphosphonates.

Question 5

Recombinant PTH analog

Answer 5

Teriparatide

Question 6

What is teriparatide’s mechanism of action?

Answer 6

Increases osteoblastic activity; osteoblasts express PTH receptor

Question 7

How is teriparatide administered?

Answer 7

Given subcutaneously daily

Question 8

Clinical use of teriparatide

Answer 8

Osteoporosis; causes increased bone growth compared to antiresorptive therapies (e.g., bisphosphonates)

Question 9

Toxicities associated with teriparatide

Answer 9

1. Transient hypercalcemia

2. May increase risk of osteosarcoma

Question 10

Give some examples of different NSAIDs.

Answer 10

1. Ibuprofen
2. Naproxen
3. Indomethacin
4. Ketorolac
5. Diclofenac

Question 11

Mechanism by which NSAIDs work

Answer 11

Reversibly inhibit cyclooxygenase (both COX-1 and COX-2) and thus block prostaglandin synthesis

Question 12

Which NSAID is used to close a PDA?

Answer 12

Indomethacin

Question 13

Clinical uses of NSAIDs

Answer 13

1. Antipyretic
2. Analgesic
3. Anti-inflammatory

Question 14

Toxicities associated with NSAIDs

Answer 14

1. Interstitial nephritis
2. Gastric ulcer (prostaglandins protect gastric mucosa)
3. Renal ischemia (prostaglandins vasodilate afferent arteriole)

Question 15

Celecoxib mechanism of action

Answer 15

Reversible inhibits specifically the cyclooxygenase (COX) 2 isoform, which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; spares COX-1, which helps maintain gastric mucosa; also spares platelet function, as TXA2 production is dependent of COX-1

Question 16

Clinical uses of celecoxib

Answer 16

1. Rheumatoid arthritis

2. Osteoarthritis

Question 17

Celecoxib toxicities include…

Answer 17

1. Increased risk of thrombosis

2. Sulfa allergy

Question 18

Aspirin’s mechanism of action

Answer 18

Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) via acetylation, which decreases synthesis of TXA2 and prostaglandins

Question 19

Aspirin increases the…, but has no effect on…

Answer 19

Bleeding time; PT and PTT

Question 20

Clinical uses of aspirin

Answer 20

1. Low dose ( decreases platelet aggregation
2. Intermediate dose (300-2400 mg/day) –> antipyretic/analgesic
3. High dose (2400-4000 mg/day) –> anti-inflammatory

Question 21

Toxicities associated with aspirin use

Answer 21

1. Gastric ulceration
2. Tinnitus (CN VIII)
3. Chronic use can lead to acute renal failure, interstitial nephritis, and GI bleeding
4. Risk of Reye syndrome in children treated with aspirin for viral infection
5. Causes respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis