Updated: 3/1/2018

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

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Snapshot
  • A 40-year-old woman with a past medical history of alcoholism presents to her physician's office for pain with swallowing. She had been experiencing heartburn for the past few weeks. She also reports pain with swallowing for the past few days. She reports having occasional abdominal pain and severe migraines for which she had been taking multiple doses of aspirin and ibuprofen daily. She reports variable intake during the day but consistent intake of ibuprofen at bedtime. This is often done without water. She is counseled on the side effects of nonsteroidal anti-inflammatory drugs and given alternative medication for her migraines. (Pill-induced esophagitis)
Introduction
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
    • categories of NSAIDs
      • non-selective NSAIDs
      • aspirin
      • cyclooxygenase (COX)-2 inhibitors
  • Mechanism
    • inhibits COX-1, COX-2, or both
    • ↓ formation of prostaglandins and thromboxanes
Non-Selective NSAIDs
  • Drugs
    • diclofenac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen, piroxicam
  • Mechanism
    • reversible inhibition of COX-1 and COX-2
  • Clinical uses
    • used as an analgesic, antipyretic, and anti-inflammatory medication
    • used for niacin-induced red and flushed face
    • indomethacin, specifically, is used to close the patent ductus arteriosus
  • Toxicity
    • interstitial nephritis
    • renal ischemia
      • ↓ prostaglandin (PG) E2 and PGI2 results in vasoconstriction of afferent arteriole
      • renal papillary necrosis
    • aplastic anemia
    • gastric ulcers and bleeding
      • ↓ PGE2 and PGE1 results in ↓ gastric mucosal protection
    • pill-induced esophagitis
Aspirin
  • Drug
    • aspirin (acetylsalicylic acid) is converted to salicylic acid in the body
  • Mechanism
    • irreversible inhibition of COX-1 and COX-2 by covalent acetylation
  • Clinical uses
    • anti-platelet aggregation at low doses (< 300 mg/day)
    • antipyretic and analgesic at intermediate doses (300-2400 mg/day)
    • anti-inflammatory medication at high doses (2400-4000 mg/day)
  • Toxicity
    • chronic toxicity
      • interstitial nephritis
      • acute renal failure
      • gastric ulcers and bleeding
      • pill-induced esophagitis
      • decreases uric acid excretion
        • avoid using aspirin in those with gout
    • acute toxicity
      • tinnitus and vertigo
      • nausea and vomiting
      • altered mental status
      • noncardiac pulmonary edema
      • mixed metabolic acidosis and respiratory alkalosis 
        • respiratory alkalosis early on from stimulation of respiratory centers in the medulla
        • anion-gap metabolic acidosis from interference with oxidative phosphorylation and Krebs cycle, resulting in accumulation of lactic acid and ketoacids
      • treatment
        • sodium bicarbonate
    • if used in children with viral infection, aspirin increases the risk for Reye syndrome
Selective COX-2 Inhibitors
  • Drug
    • celecoxib
  • Mechanism
    • reversible inhibition of COX-2
      • specifically targets inflammatory cells and vascular endothelium
    • spares COX-1
      • maintains the gastric mucosa and platelets
      • less gastrointestinal toxicity
  • Clinical use
    • anti-inflammatory and analgesic medication
    • typically used in rheumatoid arthritis and osteoarthritis
  • Toxicity
    • ↑ risk of thrombosis
    • cross-hypersensitivity to sulfonamides
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MK.27) A 59-year-old male with a 1-year history of bilateral knee arthritis presents with epigastric pain that intensifies with meals. He has been self-medicating with aspirin, taking up to 2,000 mg per day for the past six months. Which of the following medications, if taken instead of aspirin, could have minimized his risk of experiencing this epigastric pain? Review Topic

QID: 107009
1

Ketorolac

1%

(1/103)

2

Indomethacin

3%

(3/103)

3

Naproxen

3%

(3/103)

4

Ibuprofen

4%

(4/103)

5

Celecoxib

88%

(91/103)

M1

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PREFERRED RESPONSE 5
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(M1.MK.50) A 49-year-old man being treated for Helicobacter pylori infection presents to his primary care physician complaining of lower back pain. His physician determines that a non-steroidal anti-inflammatory drug (NSAID) would be the most appropriate initial treatment. Which of the following is the most appropriate NSAID for this patient? Review Topic

QID: 101360
1

Aspirin

3%

(3/93)

2

Ibuprofen

13%

(12/93)

3

Codeine

1%

(1/93)

4

Bismuth

10%

(9/93)

5

Celecoxib

73%

(68/93)

M1

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PREFERRED RESPONSE 5
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