Updated: 1/23/2017

Anti-inflammatory Medications

Topic
Review Topic
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Questions
9
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Evidence
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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
  • 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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Questions (9)

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

QID: 3109
1

Local flare in surrounding tissues

6%

(135/2124)

2

Apoptosis of myocytes

50%

(1064/2124)

3

Skin pigmentation changes

2%

(45/2124)

4

Fat atrophy

3%

(60/2124)

5

Facial flushing

38%

(813/2124)

ML 4

Select Answer to see Preferred Response

PREFERRED RESPONSE 2
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(OBQ13.142) Which of the following side effects is most strongly associated with the use of NSAIDs? Review Topic

QID: 4777
1

Hepatic dysfunction

3%

(108/3730)

2

Renal impairment

94%

(3502/3730)

3

Prolonged QTc

1%

(37/3730)

4

Seizures

0%

(7/3730)

5

Hematuria

2%

(61/3730)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

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

QID: 867
1

Carbonic anhydrase

5%

(94/1811)

2

HMG-CoA reductase

6%

(114/1811)

3

1-lipoxygenase

5%

(97/1811)

4

Cyclooxygenase

78%

(1404/1811)

5

Thromboxane synthetase

5%

(92/1811)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

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

QID: 3164
1

Meloxicam

12%

(305/2542)

2

Diclofenac

3%

(70/2542)

3

Indomethacin

2%

(56/2542)

4

Naproxen sodium

1%

(31/2542)

5

Aspirin

81%

(2071/2542)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

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

QID: 3470
1

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

7%

(122/1636)

2

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

16%

(267/1636)

3

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

60%

(985/1636)

4

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

12%

(194/1636)

5

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

4%

(60/1636)

ML 3

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(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? Review Topic

QID: 85
1

Renal failure

10%

(37/383)

2

Hepatitis

0%

(0/383)

3

Peripheral neuropathy

1%

(2/383)

4

Deep vein thrombosis

0%

(0/383)

5

Gastrointestinal ulceration

89%

(342/383)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5
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