Updated: 6/17/2021

Anti-inflammatory Medications

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  • Introduction
    • Non-steroidal anti-inflammatory drugs (NSAIDS) have the following effects
      • anti-inflammatory
      • antipyretic
      • analgesic
      • antiplatelet
    • Mechanism
      • inhibit the COX (cyclooxygenase) enzymes ultimately inhibiting the synthesis and release of prostaglandins
        • COX enzymes catalyze the formation of prostaglandins and thromboxane from arachidonic acid
      • There are two different COX enzymes targeted
        • COX inhibitors
          • target both COX-1 and COX-2
        • COX-2 specific inhibitors
          • target COX-2 alone and do not affect COX-1 function
    • Indications
      • pain
      • heterotopic ossfication prophylaxis
    • Contraindications
      • severe renal disease
      • gastric ulcers
  • COX Inhibitors
    • NSAIDS inhibit both COX-1 and COX-2
      • Aspirin (ASA)
        • salicylate that irreversibly binds a serine COX enzyme residue
        • half life >1 week
        • binds to COX and blocks active site
        • inhibits thromboxane A2 blocking platelet aggregation
      • ibuprofen
        • reversible competitive COX inhibitor
      • indomethacin
        • acts on the lipoxygenase side of the arachidonic metabolic pathway
        • inhibibits leukotriene inflammatory mediators
  • COX-2 Specific Inhibitors
    • Introduction
      • selectively target COX-2 enzymes and do not affect COX-1 function
        • examples
          • celecoxib (Celebrex)
          • rofecoxib (Vioxx)
    • Benefits
      • selective inhibition of COX-2 results in anti-inflammatory action without disrupting the beneficial effects of COX-1 (maintaining gastric mucosa, regulating renal blood flow, influencing platelet aggregation)
      • can be used in the perioperative period because they do not affect platelet function
      • no more efficacious in treating osteoarthritis than non-specific COX inhibitors
    • Side effects
      • cardiac toxicity
  • Side Effects
    • Renal dysfunction
    • Gastrointestinal side effects
      • pain and dyspepsia
      • peptic ulcer perforation, bleeding, or obstruction
        • 2% to 4% occurence in chronic users
      • risk factors
        • concurrent anticoagulant use (most important)
        • age >60 years
        • history of previous gastrointestinal disorder
    • Delayed fracture healing
      • animal fracture models have shown decreased endochondral ossification in the absence of a COX-2 enzyme
      • delayed union and nonunion due to inhibition of chondrogenic differentiation of mesenchymal stem cells
        • inhibit callus formation by inhibiting endochondral ossification
        • secondary bone healing more likely to be effected than primary bone healing
      • Increased risk with prolonged use, large doses, and adult patients
        • no effect demonstrated in pediatric fracture healing
    • Platelet dysfunction
    • Cardiac Toxicity
  • Corticosteroids (Systemic)
    • Steroid Dose Pack
      • efficacy
      • side effects
  • Corticosteroid Intra-articular-Injections
    • Efficacy
    • Side Effects
      • Local flare
      • Fat atrophy
      • Skin pigmentation changes
      • Facial flushing
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(OBQ13.142) Which of the following side effects is most strongly associated with the use of NSAIDs?

QID: 4777
1

Hepatic dysfunction

3%

(144/4758)

2

Renal impairment

94%

(4468/4758)

3

Prolonged QTc

1%

(43/4758)

4

Seizures

0%

(8/4758)

5

Hematuria

2%

(72/4758)

L 1 B

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(OBQ11.47) Which of the following is true regarding the COX-2 enzyme?

QID: 3470
1

It regulates normal cellular processes and is the primarily constitutive form of the COX enzymes

7%

(142/1936)

2

It decreases prostaglandin production in bone in the presence of certain osteotropic factors

17%

(331/1936)

3

It is thought to be necessary for normal endochondral ossification during fracture healing

59%

(1134/1936)

4

Inhibition of COX-2 has been definitively shown to impede bone healing in human clinical studies

12%

(241/1936)

5

Pharmocologic COX-2 inhibition commonly leads to more gastric irritation than COX-1 inhibition

4%

(79/1936)

L 3 C

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(OBQ10.21) Which of the following is NOT a described complication of corticosteroid injections?

QID: 3109
1

Local flare in surrounding tissues

6%

(151/2338)

2

Apoptosis of myocytes

51%

(1182/2338)

3

Skin pigmentation changes

2%

(47/2338)

4

Fat atrophy

3%

(81/2338)

5

Facial flushing

37%

(868/2338)

L 4 D

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(OBQ10.76) All the following medications binds reversibly to the enzyme COX-1 EXCEPT

QID: 3164
1

Meloxicam

13%

(399/3074)

2

Diclofenac

3%

(85/3074)

3

Indomethacin

3%

(92/3074)

4

Naproxen sodium

2%

(59/3074)

5

Aspirin

79%

(2429/3074)

L 2 D

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(OBQ07.206) Arachidonic acid is directly metabolized by which of the following substances?

QID: 867
1

Carbonic anhydrase

5%

(118/2205)

2

HMG-CoA reductase

7%

(147/2205)

3

1-lipoxygenase

5%

(119/2205)

4

Cyclooxygenase

77%

(1705/2205)

5

Thromboxane synthetase

5%

(106/2205)

L 2 D

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(OBQ05.49) A 45-year-old man is placed on indomethacin for heterotopic ossification prophylaxis following surgery for an acetabular fracture. What is the most likely side effect of this medication?

QID: 85
1

Renal failure

10%

(63/651)

2

Hepatitis

0%

(2/651)

3

Peripheral neuropathy

1%

(8/651)

4

Deep vein thrombosis

0%

(1/651)

5

Gastrointestinal ulceration

88%

(575/651)

L 1 D

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