MS - Pharm (Part 2: Biphosphonates, Gout drugs, & TNF-alpha inhibitors)

Question 1

What is an example of Bisphosphonates? In what suffix do they usually end?

Answer 1

Alendronate, other -dronates

Question 2

What are the mechanism and effects of Bisphosphonates?

Answer 2

Pyrophosphate analogs; Bind hydroxyapatite in bone, inhibiting osteoclast activity

Question 3

What are 3 clinical uses for Bisphosphonates?

Answer 3

(1) Osteoporosis (2) Hypercalcemia (3) Paget disease of bone

Question 4

What are 2 toxicities of Bisphosphonates?

Answer 4

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

Question 5

What musculoskeletal drug is known for its corrosive esophagitis toxicity? How is this managed/prevented clinically?

Answer 5

Biphosphonates; Corrosive esophagitis (patients are advised to take with water and remain upright for 30 minutes)

Question 6

What are 3 chronic (preventive) gout drugs?

Answer 6

(1) Allopurinol (2) Febuxostat (3) Probenecid

Question 7

What are the mechanism and effect of Allopurinol?

Answer 7

Inhibits xanthine oxidase, decreasing conversion of xanthine to uric acid

Question 8

Besides gout, in what other clinical conditions is Allopurinol used, and why?

Answer 8

Also used in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy

Question 9

What 2 drug concentrations does Allopurinol affect, and how/why?

Answer 9

Increase concentrations of azathioprine and 6-MP (both normally metabolized by xanthine oxidase).

Question 10

What type of drugs should not be given with Allopurinol, and why?

Answer 10

Do not give salicylates; All but the highest doses depress uric acid clearance. Even high doses (5-6 g/day) have only minor uriocosuric activity.

Question 11

What is the mechanism of Febuxostat? What other drug shares this mechanism?

Answer 11

Inhibits xanthine oxidase; Allopurinol

Question 12

What are the mechanisms of Probenecid?

Answer 12

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

Question 13

What are 3 types of acute gout drugs?

Answer 13

(1) NSAIDs (2) Glucocorticoids (3) Colchicine

Question 14

What are 2 examples of NSAIDs used as acute gout drugs?

Answer 14

(1) Naproxen (2) Indomethacin

Question 15

What are 2 administration routes for glucocorticoids used as acute gout drugs?

Answer 15

(1) Oral or (2) Intraarticular

Question 16

What are the mechanism and effects of Colchicine?

Answer 16

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

Question 17

Is Colchicine valuable as an acute or prophylactic intervention for gout?

Answer 17

Acute and prophylactic value

Question 18

What kind of side effects are associated with Colchicine use?

Answer 18

GI side effects

Question 19

Draw a diagram showing the major steps in the progression from Purines entering the body to being excreted in the urine. Include and label the steps at which each of the following drugs act: (1) Allopurinol, Febuxostat (2) Diuretics and low-dose salicylates (3) Probenecid and high-dose salicylates.

Answer 19

See p. 441 in First Aid 2014 for visual at top right of page

Question 20

What are 2 sources of Purines in the body?

Answer 20

(1) Diet (2) Nucleic acids

Question 21

What are the major steps taken by Purines to become plasma uric acid? What roles do Xanthine oxidase play in this context?

Answer 21

Purines => Hypoxanthine => Xanthine => Plasma uric acid; Xanthine oxidase catalyzes formation of Xanthine AND Plasma uric acid

Question 22

What INHIBITS tubular absorption versus secretion of uric acid?

Answer 22

INHIBITORS OF TUBULAR ABSORPTION: Probenecid and high-dose salicylates; INHIBITORS OF TUBULAR SECRETION: Diuretics and low-dose salicylates

Question 23

To what general condition do all TNF-alpha inhibitors predispose, and why? Give a particular example of this.

Answer 23

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

Question 24

What are 3 examples of TNF-alpha inhibitors?

Answer 24

Etanercept, Infliximab, Adalimumab

Question 25

What is the mechanism of Etanercept? How is it made?

Answer 25

Fusion protein (receptor for TNF-alpha + IgG1 Fc), produced by recombinant DNA; Think: “etanerCEPT is a TNF decoy reCEPTor”

Question 26

What is the mechanism of Infliximab? What other drug shares this mechanism?

Answer 26

Anti-TNF-alpha monoclonal antibody; Adalimumab

Question 27

What are 3 clinical uses for Etanercept?

Answer 27

(1) Rheumatoid arthritis (2) Psoriasis (3) Ankylosing spondylitis

Question 28

What are 4 clinical uses for Infliximab, Adalimumab?

Answer 28

(1) IBD (2) Rheumatoid arthritis (3) Ankylosing spondylitis (4) Psoriasis