Musculoskeletal, Skin, and Connective Tissue Pharmacology

Question 1

acetaminophen–mechanism

Answer 1

• reversibly inhibits cyclooxgenase
  
  • mostly in CNS
• inactivated peripherally

Question 2

acetaminophen–use

Answer 2

• antipyretic
• analgesic
• NOT anti-inflammatory
• used instead of aspirin to avoid Reye syndrome in children with a viral infection

Question 3

acetaminophen–toxicity

Answer 3

• overdose produces hepatic necrosis
  
  • acetaminophen metabolic (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver

Question 4

acetaminophen–antidote

Answer 4

• N-acetylcysteine
  
  • regenerates glutathione

Question 5

aspirin–mechanism

Answer 5

• NSAID that irreversibly inhibits cyclooxygenase (COX-1 and COX-2) by covalent acetylation –> dec synthesis of TXA2 and prostaglandins
  
  • inc bleeding time
  • no effect on PT, PTT
  • effect lasts until new platelets are produced

Question 6

aspirin–use

Answer 6

• low dose (<300 mg/day): dec platelet aggregation
• intermediate dose (300-2400 mg/day): antipyretic and analgesic
• high dose (2400-4000 mg/day): anti-inflammatory

Question 7

aspirin–toxicity

Answer 7

• gastric ulceration
• tinnitus (CN VIII)
• chronic use can lead to:
  
  • acute renal failure
  • interstitial nephritis
  • GI bleeding
• causes respiratory alkalosis early, but transitions to mixed metabolic acidosis respiratory alkalosis

Question 8

what are children at risk for if have a viral infection that is treated with aspirin?

Answer 8

Reye syndrome

Question 9

celecoxib–mechanism

Answer 9

• reversibly inhibits specifically the cyclooxogenase (COX) isoform 2 which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain
  
  • spares COX 1

Question 10

what are the benefits of using celecoxib over other NSAIDs?

Answer 10

• spares COX-1 which helps maintain gastric mucosa
  
  • so does not have the corrosive effects of other NSAIDs on the GI lining
• spares platelet function as TXA2 production is dependent on COX-1

Question 11

celecoxib–use

Answer 11

• rheumatoid arthritis
• osteoarthritis

Question 12

celecoxib–toxicity

Answer 12

• inc risk of thrombosis
• sulfa allergy

Question 13

name the NSAIDs

Answer 13

• ibuprofen
• naproxen
• indomethacin
• ketorolac
• diclofenac
• meloxican
• piroxican

Question 14

NSAIDs–mechanism

Answer 14

• reversibly inhibit cyclooxygenase (both COX 1 and 2)
• blocks prostaglandin synthesis

Question 15

NSAIDs–use

Answer 15

• antipyretic
• analgesic
• anti-inflammatory
• indomethacin is used to close a patent ductus arteriosis

Question 16

NSAIDs–toxicity

Answer 16

• interstitial nephritis
• gastric ulcer–prostaglandins protect gastric mucosa
• renal ischemia–prostaglandins vasodilate afferent arteriole

Question 17

leflunomide–mechanism

Answer 17

• reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis
• suppresses T cell proliferation

Question 18

leflunomide–use

Answer 18

• rheumatoid arthritis
• psoriatic arthritis

Question 19

leflunomide–toxicity

Answer 19

• diarrhea
• HTN
• hepatotoxicity
• teratogenicity

Question 20

name the bisphosphonates

Answer 20

• alendronate
• ibandronate
• risedronate
• zoledronate

Question 21

bisphosphonates–mechanism

Answer 21

• pyrophosphate analogs
• bind hydroxyapatite in bone
  
  • inhibits osteoclast activity

Question 22

bisphosphonates–use

Answer 22

• osteoporosis
• hypercalcemia
• Paget dz of the bone
• metastatic bone dz
• osteogenesis imperfecta

Question 23

bisphosphonates–toxicity

Answer 23

• esophagitis
  
  • if taken orally, patients are advised to take with water and remain upright for 30 minutes
• osteonecrosis of jaw
• atypical stress fractures

Question 24

teriparatide–mechanism

Answer 24

• recombinant PTH analog given subcutaneously daily
• inc osteoblastic activity

Question 25

teriparatide–use

Answer 25

• osteoporosis
  
  • causes inc bone growth compared to antiresorptive therapies
    
    • ie. bisphosphonates

Question 26

teriparatide–toxicity

Answer 26

• transient hypercalcemia

Question 27

name the chronic gout drugs (preventive)

Answer 27

• allopurinol
• febuxostat
• pegloticase
• probenecid

Question 28

name the acute gout drugs

Answer 28

• NSAIDs
• glucocorticoids
• colchicine

Question 29

allopurinol–mechanism

Answer 29

• competitive inhibitor of xanthine oxidase
  
  • decrease conversion of hypoxanthine and xanthine to urate
• increase concentrations of azathioprine and 6 MP
  
  • both normally metabolized by xanthine oxidase

Question 30

other uses for allopurinol besides gout

Answer 30

• used in lymphoma and leukemia to prevent tumor lysis–associated urate nephropathy

Question 31

febuxostat–mechanism

Answer 31

• inhibits xanthine oxidase

Question 32

pegloticase–mechanism

Answer 32

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

Question 33

probenecid–mechanism

Answer 33

• inhibits reabsorption of uric acid in the proximal convoluted tubule
  
  • also inhibits secretion of penicillin
  • can precipitate uric acid calculi

Question 34

name the NSAIDs used for gout

Answer 34

• naproxen
• indomethacin

Question 35

what type of NSAID should not be used for acute gout and why?

Answer 35

• salicylates
  
  • all but the highest doses depress uric acid clearance
  • even high doses (5-6 g/day) have only minor uricosuric acitvity

Question 36

glucocorticoids–mechanism for use in acute gout

Answer 36

• oral
• intra-articular
• parenteral

Question 37

colchicine–mechanism

Answer 37

• binds and stabilizes tubulin to inhibit microtubule polymerization
  
  • impairs neutrophil chemotaxis and degranulation

Question 38

colchicine–use

Answer 38

acute and prophylactic use for gout

Question 39

colchicine–toxicity

Answer 39

GI side effects

Question 40

name 2 TNF alpha inhibitors

Answer 40

• etanercept
• infliximab, adalimumab

Question 41

what do TNF alpha inhibitors predispose a patient to and why?

Answer 41

• all TNF alpha inhibitors predispose to infection, including reactivation of latent TB
  
  • b/c TNF is important in granuloma formation and stabilization

Question 42

etanercept–mechanism

Answer 42

• fusion protein–receptor for TNF alpha + IgG1 Fc
  
  • produced by recombinant DNA
    
    • “Etanercept is a TNF decoy receptor”

Question 43

etanercept–use

Answer 43

• rheumatoid arthritis
• psoriasis
• ankylosing spodylitis

Question 44

infliximab, adalimumab–mechanism

Answer 44

• anti TNF alpha monoclonal antibody

Question 45

infliximab, adalimumab–use

Answer 45

• inflammatory bowel disease
• rheumatoid arthritis
• ankylosing spondylitis
• psoriasis

Question 46

rasburicase–mechanism

Answer 46

• recombinant uricase that catalyzes metabolism of uric acid to allantoin

Question 47

rasburicase–use

Answer 47

• prevention and treatment of tumor lysis syndrome