NSAIDs

NSAID

A non-steroidal anti-inflammatory drug that primarily inhibits cyclo-oxygenase.

COX inhibitor

Another name for an NSAID based on its primary mechanism.

Cyclo-oxygenase (COX)

An enzyme that metabolizes arachidonic acid into endoperoxide intermediates and prostanoids.

Arachidonic acid

A membrane fatty acid used as the substrate for COX.

Prostanoids

Products generated downstream of COX activity.

PGD2

A prostanoid produced downstream of COX activity.

PGE2

A prostanoid involved in multiple physiological effects.

PGF2α

A prostanoid produced downstream of COX activity.

PGI2

Prostacyclin, a prostanoid produced downstream of COX activity.

TXA2

Thromboxane A2, a prostanoid produced downstream of COX activity.

COX-1

A constitutive COX isoform involved in normal stomach, kidney, vascular, and platelet functions.

COX-2

A COX isoform involved in inflammation, pain, fever, and other physiological processes.

COX-1 gastrointestinal role

COX-1-derived PGE2 inhibits stomach acid secretion and supports mucosal protection.

COX-1 platelet role

COX-1-derived thromboxane promotes platelet aggregation.

COX-2 platelet role

COX-2-derived prostacyclin inhibits platelet aggregation.

NSAID anti-inflammatory effect

Primarily due to COX-2 inhibition.

NSAID analgesic effect

Primarily due to COX-2 inhibition.

NSAID antipyretic effect

Primarily due to COX-2 inhibition.

NSAID GI effects

Primarily due to inhibition of COX-1.

NSAID renal effects

NSAIDs can promote sodium retention and increase blood pressure.

NSAID kidney risk

Patients with compromised kidneys, especially elderly or volume-depleted patients, are at risk for renal ischemia.

Renal prostaglandins

Help maintain renal perfusion in compromised kidneys by dilating afferent arterioles.

NSAID GI protection

COX-1-derived prostaglandins inhibit acid secretion, increase mucosal blood flow, and promote protective mucus.

NSAID GI toxicity

COX-1 inhibition can cause dyspepsia, heartburn, ulcers, and GI bleeding.

NSAID wound healing effect

COX-2-derived prostaglandins promote wound healing, so NSAIDs can slow healing.

NSAID gestational effect

COX-2 inhibition can prolong gestation because prostaglandins participate in labor.

Aspirin

Acetylsalicylic acid and a prototype nonselective NSAID.

Aspirin mechanism

Irreversibly inhibits COX by acetylating an active-site serine.

Aspirin platelet effect

Platelets are particularly sensitive to aspirin because aspirin irreversibly inhibits COX.

Aspirin GI toxicity

Can cause GI distress and bleeding.

Aspirin bleeding effect

Prolongs bleeding time.

Aspirin contraindication

Contraindicated in patients taking warfarin according to the lecture.

Aspirin children contraindication

Contraindicated in children with chickenpox or influenza because of Reye's syndrome risk.

Salicylism

Toxicity from salicylates.

Mild salicylism

Headache, dizziness, sweating, and tinnitus.

Severe salicylism

CNS disturbances, fever, nausea, and acid-base disturbances.

Ibuprofen

A non-salicylate NSAID.

Naproxen

A non-salicylate NSAID.

Celecoxib

A COX-2 selective NSAID.

COX-2 selective NSAID

An NSAID designed to preferentially inhibit COX-2.

Acetaminophen

An analgesic and antipyretic with little anti-inflammatory activity.

Acetaminophen GI effect

Typically does not cause GI distress.

Acetaminophen platelet effect

Does not affect platelet function.

Acetaminophen toxicity

High doses can cause hepatotoxicity.

NAPQI

A toxic acetaminophen metabolite that depletes glutathione.

Glutathione

A substance depleted during acetaminophen toxicity that normally helps detoxify NAPQI.

Acetaminophen overdose mechanism

Glutathione depletion allows toxic metabolites to cause cellular damage.

Acetylcysteine

A sulfhydryl reagent used to treat acetaminophen overdose.

Acetylcysteine mechanism

Replenishes glutathione levels during acetaminophen toxicity.

NSAID cardiovascular prostanoids

COX-1-derived thromboxane promotes platelet aggregation while COX-2-derived prostacyclin inhibits it.

NSAID renal blood pressure effect

NSAIDs can slightly elevate blood pressure.

NSAID drug list

Aspirin, ibuprofen, naproxen, celecoxib, acetaminophen, and acetylcysteine.