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Chapter 42: Pharmacotherapy of Inflammation, Fever, Pain, and Gout

Tilo Grosser; Emanuela Ricciotti; Garret A. FitzGerald

INTRODUCTION

This chapter describes the nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat inflammation, pain, and fever and the drugs used for hyperuricemia and gout. The NSAIDs are first considered by class, then by groups of chemically similar agents described in more detail. Many of the basic properties of these drugs are summarized in Tables 42–1, 42–2, and 42–3.

TABLE 42–1SOME SHARED ADVERSE EFFECTS OF NSAIDsa
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TABLE 42–1 SOME SHARED ADVERSE EFFECTS OF NSAIDsa
SYSTEM MANIFESTATIONS
Gastrointestinal Abdominal pain, bleeding, constipation, diarrhea, dyspepsia, dysphagia, eructation,b esophageal stricture/ulceration, esophagitis, flatulence, gastritis, hematemesis,b melena,b nausea, odynophagia, perforation, pyrosis, stomatitis, ulcers, vomiting, xerostomiab
Platelets Inhibited platelet activation,b propensity for bruising,b increased risk of hemorrhage,b platelet dysfunction,b thrombocytopeniab
Renal Azotemia,b cystitis,b dysuria,b hematuria, hyponatremia, interstitial nephritis, nephrotic syndrome,b oliguria,b polyuria,b renal failure, renal papillary necrosis, proteinuria, salt and water retention, hypertension, worsening of renal function in renal/cardiac/cirrhotic patients, effectiveness of antihypertensives and diuretics, hyperkalemia,b ↓ urate excretion (especially with aspirin)
Cardiovascular Edema,b heart failure,c hypertension, MI,c palpitations,b premature closure of ductus arteriosus, sinus tachycardia,b stroke,c thrombosis,c vasculitisb
Neurologic Anorexia,b anxiety,b aseptic meningitis, confusion,b depression, dizziness, drowsiness,b headache, insomnia,b malaise,b paresthesias, tinnitus, seizures,b syncope,b vertigob
Reproductive Prolongation of gestation, inhibition of labor, delayed ovulation
Hypersensitivity Anaphylactoid reactions, angioedema, severe bronchospasm, urticaria, flushing, hypotension, shock
Hematologic Anemia, agranulocytosis, aplastic anemia,b hemolytic anemia,b leukopeniab
Hepatic Elevated enzymes, hepatitis, hepatic failure,b jaundice
Dermatologic Diaphoresis,b exfoliative dermatitis, photosensitivity,b pruritus, purpura,b rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Respiratory Dyspnea,b hyperventilation (salicylates)
Other Alopecia,b blurred vision,b conjunctivitis,b epistaxis,b fever,b hearing loss,b pancreatitis,b paresthesias, visual disturbance,b weight gainb

aRefer to product label for specific information.

bReported for most, but not all, NSAIDs.

cWith the exception of low-dose aspirin.

TABLE 42–2NSAIDs: SALICYLATES, ACETAMINOPHEN, AND ACETIC ACID DERIVATIVES
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TABLE 42–2 NSAIDs: SALICYLATES, ACETAMINOPHEN, AND ACETIC ACID DERIVATIVES
CLASS/DRUG PHARMACOKINETICS DOSING COMMENTS COMPARED TO ASPIRIN
Salicylates
Aspirin

Peak Cp, 1 h

Protein binding, 80%–90%

Metabolite, salicyluric acid

t1/2, therapeutic, 2–3 h

t1/2, toxic dose, 15–30 h

Antiplatelet, 40–80 mg/day

Pain/fever, 325–650 mg every 4–6 h

Rheumatic fever, children 1 g every 4–6 h or 10 mg/kg every 4–6 h

Permanent platelet COX-1 inhibition

Adverse effects: GI, ↑clotting time hypersensitivity

Avoid in children with acute febrile illness (Reye syndrome)

  
Diflunisal

Peak Cp, 2–3 h

Protein binding, 99%

Metabolite, glucuronide

t1/2, 8–12 h

250–500 mg every 8–12 h (maximum = 1 g/dose and 4 g/day); children <12 y: 10–15 mg/kg every 4 h (maximum ...

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