DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION IV
INFLAMMATION, IMMUNOMODULATION, AND HEMATOPOIESIS
Table 34–1
Classification and Comparison of Nonsteroidal Analgesics
CLASS/DRUG
(SUBSTITUTION) PHARMACOKINETICS DOSING d COMMENTS COMPARED TO ASPIRIN
Salicylates
Aspirin
a
Peak C p
1 hour Antiplatelet 40-80 mg/day Permanent platelet
(acetyl ester) Protein binding 80-90% Pain/fever 325-650 mg every COX-1 inhibition
Metabolites b Salicyluric acid 4-6 hours (acetylation)
t 1/2c
, therapeutic 2-3 hours Rheumatic fever 1 g every 4-6 hours Main side effects:
t 1/2
, toxic dose 15-30 hours Children 10 mg/kg every GI, increased bleeding
4-6 hours time, hypersensitivity
Avoid in children with
acute febrile illness
Diflunisal Peak C p
2-3 hours 250-500 mg every 8-12 hours Not metabolized to Analgesic and anti-
(defluoro- Protein binding 99% salicylic acid inflammatory effects
phenyl) Metabolites Glucuronide Competitive COX 4-5 times more
t 1/2
8-12 hours inhibitor potent
Excreted into breast milk Antipyretic effect
weaker
Fewer platelet and
GI side effects
Para-aminophenol derivative
Acetaminophen Peak C p
30-60 minutes 10-15 mg/kg every 4 hours Weak nonspecific Analgesic and
Protein binding 20-50% (maximum of 5 doses/24 hours) inhibitor at common doses antipyretic effects
Metabolites Glucuronide Potency may be modulated equivalent
conjugates (60%); by peroxides Anti-inflammatory,
sulfuric acid Overdose leads to GI, and platelet
conjugates (35%) production of toxic effects less than
t 1/2
2 hours metabolite and liver aspirin at
necrosis
1000 mg/day
Acetic acid derivatives
Indomethacin Peak C p
1-2 hours 25 mg 2-3 times/day; Side effects (3-50% of 10-40× more
(methylated Protein binding 90% 75-100 mg at night patients): frontal headache, potent; intolerance
indole) Metabolites O-demethylation neutropenia, limits dose
(50%); thrombocytopenia; 20%
unchanged (20%)
discontinue therapy
2.5 hours
t 1/2