Cyclooxygenase Inhibitors: Nonsteroidal Anti-Inflammatory Drugs and
Acetaminophen
Cyclooxygenase (COX) inhibitors:
● Suppress inflammation, relieve pain, reduce fever
● Protects against MI and Stroke in ASPIRIN
● Inhibition of cyclooxygenase (COX)
○ COX is the enzyme responsible for conversion of arachidonic acid into
prostanoids (prostaglandins and related compounds)
■ Prostaglandins promote inflammation and
sensitize receptors to painful stimuli
■ COX 1 promotes synthesis of PGE2 and PGI2 which
protect gastric mucosa, promote vasodilation, maintain renal
blood flow
● Reduced gastric acid secretion
● Increased bicarbonate and cytoprotective mucus
● Maintenance of submucosal BF
■ COX 1 promotes TXA2 which stimulates platelet
aggression
■ COX 2 promotes Prostacyclin synthesis causing
vasodilation
■ Prostaglandins contribute to perception of pain and
mediate fever
■ COX derived prostaglandins promote contractions at
term (inhibition reduces prostaglandin synthesis in uterine
smooth muscle)
■ Prostaglandin, Prostacyclin and TXA2 act LOCALLY
■ COX 1: “good cox”
● Found in all tissues; “housekeeping”
● Protect gastric mucosa
● Support renal function
● Promote platelet aggression
● INHIBITION: (harmful effects)
○ Gastric erosion and ulceration
○ Bleeding tendencies
○ Renal impairment
● INHIBITION: (1 beneficial effect)
○ Protection against MI and Stroke secondary to
reduced platelet aggression
, ■ COX 2: “bad cox”
● Found at tissue injury sites
● Mediates inflammation and sensitizes receptors to painful
stimuli
● Mediates fever and contributes to perception of pain in the
brain
● Supports renal function
● Promotes vasodilation in blood vessels
● Can contribute to colon cancer
● INHIBITION: (beneficial effects)
○ Suppression of inflammation
○ Alleviation of pain
○ Reduction of fever
○ Protection against colorectal cancer
● INHIBITION: (2 adverse effects)
○ Renal Impairment
○ Promotion of MI and Stroke
● 2 Categories:
1. DRUGS THAT HAVE ANTI-INFLAMMATORY PROPERTIES→ NSAIDS:
Non-steroidal anti-inflammatory drugs
■ Aspirin
■ Ibuprofen (Advil, Motrin)
■ Naproxen (Aleve)
○ FIRST GENERATION NSAIDS:
■ INHIBIT COX 1 AND COX 2
■ Prototype=
● Only IRREVERSIBLE COX inhibitor
● Chemical family: Salicylates
○ Acetylsalicylic acid (ASA)
● Relief of mild to moderate pain (headache,
joint pain, muscle pain), reduces fever in adults by lowering
set-point (cannot use in children→ Reye’s syndrome:
encephalopathy and fatty liver degeneration; should avoid
in children and tennagers who might have influenza or
chicken pox), protects against thrombotic disorders, drug of
choice for rheumatoid arthritis, rheumatic fever,
osteoarthritis, tendinitis, bursitis and other inflammatory
disorders; modulation of T cell function, suppression of
inflammatory cell infiltration, stabilization of lysosomes,
, relief of dysmenorrhea, ~Can be more effective for post-op
pain than opioids, ineffective against severe visceral origin
pain, cannot lower normal body temperature, Toxicity
common in treating inflammatory disorders which require
long-term high dose treatment
○ → aspirin levels slightly above TR
■ Tinnitus (maximum dosage is achieved; OA
may not experience), sweating, headache,
dizziness, disturbance→ CNS stimulates
increased respiration→ increased CO2 →
respiratory alkalosis
■ d/c until symptoms subside; resume w/
decreased dosage
● Protection against MI and ischemic stroke,
suppresses TXA 2 the enzyme that promotes platelet
aggregation thereby suppressing it through irreversible
inhibition
○ heartburn, nausea gastric
perforation, occult GI bleeding (inhibition of platelet
aggregation; do not give to pts w/ bleeding disorders
and should be d/c 1 week prior to childbirth or
surgery), gastric ulceration→ increased secretion of
acid and pepsin, decreased production of
cytoprotective mucus and bicarb, decreased
submucosal BF
■ asymptomatic→ perforation and Upper GI
hemorrhage can occur w/o warning signs
■ risk factors for ulceration: previous ulcers
(screen for H. pylori), advanced age, previous
peptic ulcer disease, previous NSAID
intolerance, alcohol abuse, cigarette smoking;
if at risk PPI (omeprazole, lansoprazole) is
recommended; anemia in chronic aspirin use
○ acute, reversible, impairment of
renal function
■ Salt and water retention
■ Signs: reduced urine output, weight gain
despite diuretic use, rapid increase in serum
creatinine and BUN
