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Chapter 191: Nonsteroidal Anti-Inflammatory Drugs and Colchicine

Jonathan de Olano; Rana Biary; Patrick C. Ng; Alex Koyfman; Brit Long

CONTENT UPDATE: Colchicine Toxicity June 2021

Colchicine is an anti-flammatory agent with several therapeutic applications. It has antimitotic activity, can inhibit mitosis of rapidly dividing cells, and has a narrow therapeutic window. Colchicine overdose is unusual but can result in severe shock and death. See “Colchicine Toxicity” at the end of this chapter.

INTRODUCTION

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic agents in the United States. All share inhibition of the cyclooxygenase enzyme as a mechanism of action. NSAIDs are effective antipyretics, analgesics, and anti-inflammatory agents. Because of their large therapeutic window, acute ingestion with overdoses rarely produces serious complications.1,2 The morbidity from NSAIDs in acute overdose is far overshadowed by complications of NSAIDs at therapeutic doses, which include GI bleeding, drug-induced renal failure, and atherosclerotic heart disease.3–6

PHARMACOLOGY

NSAIDs are structurally varied compounds with common therapeutic effects (Table 191-1). NSAIDs reversibly inhibit COX, which is responsible for the production of prostaglandins from arachidonic acid. The anti-inflammatory effect of NSAIDs is through the inhibition of prostaglandin production and neutrophil migration.7 NSAIDs are antipyretics via inhibition of prostaglandin E2 in the hypothalamus. Analgesia is mediated by attenuation of prostaglandin-mediated hyperalgesia and local pain fiber stimulus.

TABLE 191-1Nonsteroidal Agents Available in the United States
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TABLE 191-1 Nonsteroidal Agents Available in the United States
Class and Agent Half-Life With Therapeutic Doses of Standard Oral Tablets or Capsules* (h) Typical Initial Adult Oral Dose (milligrams) Maximum Recommended Adult Daily Oral Dose (milligrams)
Nonselective NSAIDs
Acetic acids
 Diclofenac 2 35 TID 150
 Indomethacin 2.6–11.2 25 BID or TID 200
 Ketorolac 5 10 QID 120
 Meclofenamate 1–2 (15†) 50 QID 400
 Mefenamic acid 2 250 QID 1000
 Nabumetone <1 (22–26†) 1000 daily 2000
 Sulindac 8 (16†) 150 BID 400
 Tolmetin 5 400 TID 1800
Propionic acids
 Fenoprofen 3 300 TID 3200
 Flurbiprofen 5–8 50 BID 300
 Ibuprofen 2 400 QID

2400 (pain, dysmenorrhea)

3200 (osteoarthritis)
 Ketoprofen 2–4 50 TID 300
 Naproxen 12–17 250 BID

1000 (pain)

1500 (osteoarthritis)
 Oxaprozin 16–45 (38–57‡) 1200 daily 1800
Oxicams
 Piroxicam 50 20 daily 20
Partially selective COX-2 inhibitors
 Etodolac 6–8 200 TID 1000
 Meloxicam 20–24 5 daily 15
Selective COX-2 inhibitors
 Celecoxib 11 200 BID 400

Abbreviations: BID = twice per day; COX-2 = cyclooxygenase 2; QID = four times per day; TID = three times per day.

*Not sustained-release or enteric-coated preparations.

†Half-life of active metabolite.

‡Half-life of protein-bound drug.

CYCLOOXYGENASE

Two isoforms of COX (COX-1 and COX-2) vary in presence and distribution.8 COX-1 is present with a steady level of activity and is found primarily in blood vessels, kidneys, and the stomach. In contrast, COX-2 is found in low levels in ...

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