NSAIDs Flashcards
NSAIDs - MoA
Inhibition of prostaglandin synthesis by competitive cyclooxygenase (COX) inhibition
NSAIDs - Clinical use
Low dose: mild-moderate pain, antipyretic Higher doses: inflammation. Postop pain (often combined with opioid) Chronic pain
NSAIDs - Contraindications
Contraind: previous severe hypersensitivity to salicylates (cross-sensitivity)
Generally not recommended for second half of pregnancy
NSAIDs - Adverse effects
GI bleeding, Peptic ulcers Renal and hepatic dysfunction. Lithium toxicity. Hyperkalemia Platelet inhibition Premature closure of ductus arteriosus
NSAIDs - Interactions
Inhibit renal excretion of lithium.
Reduced clearance of aminoglycosides & methotrexates.
Interfere with antihypertensive effect of: diuretics, β-adrenoceptor antagonists, angiotensin inhibitors & others.
Potassium-sparing diuretics: hyperkalemia
Salicylates - MoA
Nonspecific inhibition of COX
Salicylates - Clinical use
Pain, fever, inflammation
Prophylaxis for MI, stroke, thromboembolic disorders
Salicylates - Contraindication
Avoid in children: Reye syndrome (in virus infected children).
Salicylates - Overdose treatment
Vomiting
IV sodium bicarbonate (alkalization of the urine, increases ionization and elimination)
Fluids, electrolytes
Salicylates - Adverse effects
Reye syndrome
Aspirin - MoA
Forms covalent, irreversible inhibition of COX in platelets
Nonspecific inhibition of COX in peripheral tissues and CNS
Aspirin - Clinical use
Analgesic
Antipyretic
Anti-inflammatory
Aspirin - Special considerations
Longer thromboxane effect than other salicylates.
Inhibits platelet aggregation
Aspirin - Adverse
Aspirin toxicity
High dose: Tinnitus (early sign of salicylate toxicity)
Hyperventilation
Fever, dehydration, severe metabolic acidosis
If not treated: Shock, coma, organ system failure, death
Hypoprothrombinemia – impairment of hemostatis and bleeding
Hypersensitivity – anaphylaxis (mostly pt with asthma, nasal polyps, chronic urticaria)
Symptoms of aspirin intolerance: vasomotor rhinitis, angioedema, urticaria
Aspirin - Interactions and contraindication
Adm with antacids: slows absorption rate
Contraindication: Persons who have has severe hypersensitivity reaction to aspirin or another salicylate should not be treated with another type of NSAID (cross-sensitivity)
Ibuprofen - MoA
Reversible and nonselective inhibition of COX
Ibuprofen, Ketoprofen, Naproxen - Clinical use
Analgesic, antipyretic and anti-inflammatory effects
Low dose: mild pain and inflammation
Higher dose: arthritis
Ibuprofen - Special considerations
Combo with H2 receptor antagonist famotidine for RA and OA (less GI ulcers)
Half-life: 2h
Ibuprofen - Adverse effects
GI irritation, nausea, dyspepsia, bleeding.
Long-term: PUD, Hepatotoxicity, renal toxicity
Failure of ingesting adequate fluid: acute renal failure
Naproxen - Special considerations
Combo with esomeprazole: arthritis, reduces risk of ulcers
Longer halflife (14h)
Acetaminophen - MoA
COX3 inhibitor
Acetaminophen - Clincal use
Mild fever and pain
Mild arthritis
Analgesic and antipyretic effects via inhibitor of COX
Acetaminophen - Special considerations
Safe for children with viral infection
Acetaminophen - Overdose treatment
Acetylcysteine
Acetaminophen - Adverse effects
Fewer GI problems
High dose: hepatic necrosis, hepatotoxicity
Long-term use: Increased risk of renal dysfunction
Acetaminophen - Interactions
Small amount converted by CYT P-450 to potentially hepatotoxic quinone intermediate
Patients at risk for hepatotoxicity (f.ex. overdose): given acetylcysteine (conjugates quinone and renders it harmless)
Indomethacin - Clinical use
Reserved for moderate/severe inflammation disorders
Patent ductus arteriosus (indomethacin inhibit synthesis of prostaglandins and causes the closure)
Indomethacin - Adverse effects
Nephrotoxicity with triamterene
Highest incidence of GI and CNS side effects
Hematologic toxicity
Indomethacin - Interaction
Reduces natriuretic effect of diuretics.
With triamterene: nephrotoxicity
Sulindac - MoA
Prodrug converted to active sulfide metabolite. Parent compound sulindac sulfoxide is inactive in COX inhibition
Sulindac - Clinical use
RA
Adenomas in polyp disease
Ketorolac - Clinical use
Analgesic activity
Post-op moderate pain in dentistry
Allergic conjunctivitis
Post-op ocular infl.
Ketorolac - Special considerations and Caution
Potent analgesic (comparable to morphine) Ophthalmic solution of ocular inflammation. Treatment limited to 5 days
Caution in patients with renal/hepatic disease
Ketorolac - Adverse effects
Fewer GI and CNS effects than opioids.
Hematologic toxicity
Increased risk of renal or hepatic impairment
Piroxicam - Clinical use
Anti-inflammatory
Chronic RA treatment
Piroxicam - Special considerations
Long half-life (50h)
Nabumetone - MoA
Weak COX inhibitory activity in vitro, but converted to active metabolites with potent inhibition in vivo
Etodolac, meloxicam - MoA
More selective for COX-2 than typical NSAIDs
Diclofenac - Clinical use
Osteoarthritis
Selective COX-2 inhibitors
Celecoxib
Rofecoxib (Removed from market)
Valdecoxib (Removed from market)
Selective COX-2 inhibitors - MoA
Potent anti-inflammatory action
Selective COX-2 inhibitors - Special
Decreased risk of cancer (esp colon cancer)
Celecoxib - Clinical use
Rheumatoid arthritis
Osteoarthritis
Celecoxib - MoA
Selective COX-2 inhibition
Analgesic
antipyretic
antiinflammatory
Celecoxib - Special
Does not inhibit platelet aggregation (platelet contain only COX-1)
Celecoxib - Adverse effects
Increased risk of cardiovascular events
Low incidence: diarrhea, dyspepsia, abd pain
Celecoxib - Interactions
Metabolized by CYT P-450
Metabolism is inhibited and increased serum levels by fluconazole, fluvastatin, zafirlukast.
