Ch. 71: Cyclooxygen Inhibitors Flashcards
Cyclooxygenase Inhibitors
Indications:
- suppress inflammation
- relieve pain
- reduce fever
Adverse Effects:
- Gastric Ulceration
- Bleeding
- Renal Impairment
Mechanism of Action
- inhibit COX, enzyme that converts arachidonic acid into prostanoids
Inhibition of COX-1 ("good COX")Inhibition of COX-1: Beneficial Effects
- protection against myocardial infarction (MI)
and stroke - (bad Effects are gastric ulceration, bleeding and renal impairment)
Inhibition of COX-2 (“bad COX): benefical effects
- suppression of inflammation
- alleviation of pain and reduction of fever
- protection against colorectal cancer
Classification of Cyclooxygenase Inhibitors
with antiinflammatory properities (nonsteroidal antiinflammatory drugs) NSAIDs
- aspirin, celecoxib, ibuprofen, and naproxen
without antiinflammatory properities (Acetaminophen)
First-Generation NSAIDs
- inhibit COX-a and COX-2
- used to treat inflammatory disorders (rheumatoid arthritis): alleviate mild to moderate pain, suppres fever, relieve dysmenorrhea
- suppress inflammation but pose risk of serious harm
Aspirin
- nonselective inhibitor of cyclooxygenase
- therapeutic uses: analgesic, antipyretic, antiinflammatory; suppression of platelet aggregation (thrombotic disorder); dysmenorrhea; cancer prevention and prevent Alzheimer’s disease
Aspirin: Adverse Effects
- GI effects
- bleeding
- renal impairment
- salicyclism: tinnitus, sweating, headache, and dizziness
- Reye’s syndrome
- pregnancy: anemia, postpartum hemorrhage, prolong labor
- hypersensitivity reaction
Aspirin: Drug Interactions
- Anticoagulants: Warfarin and heparin, glucocorticoids, alcohol, ibuprofen, ACE inhibitors and ARBs
- acute poisoning
- immediate threats to life: resp. depression, hyperthermia, dehydration, and acidosis
- treatment is largely supportive
Nonaspirin First-Generation NSAIDs
- aspirin-like drugs with fewer GI, renal, and hemorrhagic effects
- 20+ nonaspirin NSAIDs available (all similar but for unknown reasons some do better on one than another)
- inhibit COX_1 and COX-2: inhibition is reversible (unlike aspirin)
- principle indications: Rheumatoid arthritis and osteoarthritis
- do not protect against MI and stroke
First-Generation NSAIDs: Ibuprofen
- inhibit cyclooxyengase and has antiinflammatory, analgesic, and antipyretic actions
- indications: fever, mild to moderate pain, arthritis
- generally well tolerated
- low incidence of adverse effects
- SAFETY ALERT: all first-generation NSAIDs are associated with an increased risk of GI bleeding that can lead to hosp or death
Second-Generation NSAIDs
- just as effective as traditional NSAIDs in suppressing inflammation and pain
- somewhat lower risk for GI side effects
- can impair renal function and cause hypertension and edema
- increased risk of MI and stroke
Celecoxib
- 2-gen COX-2 inhibitor: fewer adverse effects than 1-gen drugs
- cardiovascular risks, last-choice drug for long-term management of pain
- uses: osteoarthritis, rheumatoid arthritis, acute pain, dysmenorrhea, familial adenomatous polyposis
Celecoxib: Adverse Effects
- Dyspepsia
- abdominal pain
- renal impairment
- sulfonamide allergy
- CV impact (stroke, MI)
- use in pregnancy
Celecoxib: Drug Interactions
- Warfarin (may decrease diuretic effect of furosemide
- may decrease antihypertensive effect of ACE inhibitors
- may increase levels of lithium
- celecoxib levels may be increased by fluconazole
Acetaminophen
therapeutic uses:
- analgesic, antipyretic
- does not have any antiinflammatory or antiheumatic actions
- not associated with Reye’s Syndrome
Action:
- inhibits prostaglandin synthesis in CNS
