Mechanism of Action

Inhibit cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostaglandins — the mediators of inflammation, pain sensitization, and fever. Blocking prostaglandin production yields three effects at once: anti-inflammatory, analgesic, and antipyretic. COX-1 is the constitutive 'housekeeping' isoform (gastric mucosal protection, platelet aggregation, renal blood flow); COX-2 is the inducible 'alarm' isoform that ramps up at sites of injury. Most NSAIDs (ibuprofen, naproxen) block both; celecoxib is COX-2 selective, sparing gastric mucosa but still carrying cardiovascular risk.

Common Medications

ibuprofenPrototype

naproxen

ketorolac

strongest analgesic NSAID; ≤5-day max

celecoxib

COX-2 selective

aspirin

irreversible platelet inhibition

Indications

mild-to-moderate pain

osteoarthritis

rheumatoid arthritis

dysmenorrhea

fever

acute musculoskeletal injury

postoperative pain

ketorolac as opioid-sparing strategy, ≤5 days

Side Effects

epigastric pain

prostaglandin loss thins gastric mucosa

dyspepsia

peptic ulceration

take with food; PPI if high GI risk

fluid retention

sodium/water retention; can worsen heart failure

hypertension

platelet inhibition

bleeding risk; celecoxib spares platelets

Contraindications & Interactions

Contraindications

active peptic ulcer disease

third-trimester pregnancy

premature ductus arteriosus closure

severe renal impairment

GFR <30 mL/min

aspirin-sensitive asthma

asthma + nasal polyps + NSAID sensitivity; applies to ALL NSAIDs

CABG perioperative period

FDA boxed warning

decompensated heart failure

sodium/water retention worsens overload

Interactions

anticoagulants

warfarin — potentiates effect; monitor INR

ACE inhibitors

additive nephrotoxicity; component of 'triple whammy'

diuretics

volume depletion + NSAID → AKI

other NSAIDs

additive GI/renal/bleeding risk, no added analgesia

Administration & Monitoring

give with food

reduces gastric irritation

monitor serum creatinine and BUN

renal function with chronic/high-dose use

monitor urine output

limit ketorolac to 5 daysHold≤5 days IV/IM/PO

high GI/renal toxicity; notify provider as limit approaches

monitor blood pressure

monitor INR with warfarin

assess for dark tarry stools

hold before surgeryHold

7–10 days for aspirin (irreversible); shorter for others by half-life

Patient Teaching

take with food

or a full glass of water; reduces gastric irritation

report black tarry stools

sign of GI bleeding

report coffee-ground emesis

stay well hydrated

protects renal perfusion

do not combine with other NSAIDs

including OTC aspirin/naproxen

avoid alcohol

additive GI bleeding risk

do not exceed prescribed dose

AKI can occur even at therapeutic doses

report swelling or weight gain

fluid retention

Report Nowescalate immediately

myocardial infarctionBlack Box

FDA boxed warning — thrombotic CV risk rises with dose/duration; contraindicated in CABG perioperative period

stroke

same boxed CV/thrombotic warning

GI bleeding Hallmark

FDA boxed warning — dark tarry stools, hematemesis, coffee-ground emesis; can be silent and fatal

acute kidney injury

rising creatinine/BUN; 'triple whammy' with ACE inhibitor + diuretic

bronchospasm

aspirin-exacerbated respiratory disease; cross-reacts across the whole class

Clinical Pearl

COX-1 is housekeeping (stomach, kidneys, platelets), COX-2 is the alarm (inflammation). Silence both and you stop the pain — but also the housekeeping. Black stool, rising creatinine, or wheezing in an NSAID client: stop, assess, and call.