NSAIDs Pharmacology Lecture Notes Tissue Injury & Inflammatory Response Initial vasoconstriction occurs immediately after injury to minimize blood loss (temporary reaction) Chemical mediators released: histamines, kinins, and prostaglandins - crucial for inflammatory response Vasodilation follows - blood vessels widen, increasing blood flow to injured area Classic inflammatory symptoms: redness (erythema), swelling (edema), pain from nerve stimulation, fever/heat NSAIDs Classification & Examples Propionic derivatives: ibuprofen, naproxen Phenomates: mefenamic acid Available OTC: salicylates, propionic acid derivatives Prescription required: COX2 inhibitors, acetic acid derivatives, oxicams, phenomates Mechanism of Action COX enzymes: cyclooxygenase (COX1 & COX2) convert arachidonic acid to prostaglandins COX1: Always active, protects stomach lining, helps platelet aggregation COX2: Activated only during tissue injury, causes inflammation and pain NSAIDs inhibit COX enzymes, preventing prostaglandin production (prostaglandin inhibitors) Primary Effects Antipyretic: reduces fever Analgesic: pain relief Anticoagulant: prevents blood clots (especially aspirin) Specific Drug Categories Salicylates (aspirin): pain, inflammation, fever, anticoagulant effects Propionic acid derivatives: mild to moderate pain (1-6 on pain scale), inflammation, fever Acetic acid derivatives: more effective for inflammation but significant GI side effects COX2 inhibitors: second generation NSAIDs with better safety profile, target COX2 specifically Oxicams: long-term use for osteoarthritis/rheumatoid arthritis, longer half-life (once daily) Phenomates: especially effective for menstrual pain Major Side Effects Gastrointestinal Dyspepsia: heartburn, indigestion, abdominal pain, nausea Long-term risks: stomach lining damage, GI bleeding, perforation (holes in stomach/intestines) Bleeding signs to monitor: dark tarry stools, bleeding gums, petechiae, ecchymosis, purpura Higher risk patients: older adults, smokers, alcohol users, pre-existing ulcers Prevention: proton pump inhibitors or H2 receptor antagonists to reduce stomach acid Kidney Effects Impaired function: reduced urine output, fluid retention, weight gain, edema Monitor: BUN and creatinine levels for kidney function Mechanism: NSAIDs reduce blood flow to kidneys, worsening function and increasing kidney disease risk Cardiovascular Risk Non-aspirin NSAIDs increase heart attack and stroke risk Prescribe at smallest effective dose Special Considerations Menstrual Pain (Dysmenorrhea) Avoid aspirin for painful menstruation with heavy bleeding Use acetaminophen 2 days before and during first 2 days of menstrual period Aspirin-Specific Risks Salicylism/Aspirin toxicity: early symptoms from overdose, can progress to electrolyte imbalances, coma, respiratory depression Serum salicylate levels: >30 mg/dL mild toxicity, >50 mg/dL severe toxicity Treatment: activated charcoal, possible hemodialysis Reye's syndrome: rare but serious condition causing liver/brain swelling in children/adolescents recovering from viral infections (flu, chickenpox) Reye's syndrome symptoms: persistent vomiting, lethargy, confusion → irritability, aggression, disorientation, seizures, loss of consciousness Avoid aspirin in children/adolescents with viral infections Drug Interactions & Precautions Glucocorticoids: amplify stomach bleeding risk Alcohol: increases stomach bleeding - limit/avoid consumption Other NSAIDs: can negate heart protective effects of aspirin - space dosing apart Herbal supplements: garlic and ginseng enhance bleeding risk High-risk populations: older adults, smokers, certain health conditions (H7

Initial occurs immediately after injury to minimize blood loss.

vasoconstriction

Chemical mediators released during the inflammatory response include , kinins, and prostaglandins.

histamines

After initial vasoconstriction, follows, increasing blood flow to the injured area.

vasodilation

Classic inflammatory symptoms include redness (erythema), swelling (edema), , and fever/heat.

pain

NSAIDs include derivatives such as ibuprofen and naproxen.

propionic

Examples of include mefenamic acid.

phenomates

NSAIDs that are available OTC include and propionic acid derivatives.

salicylates

Prescription is required for COX2 inhibitors, acid derivatives, oxicams, and phenomates.

acetic

COX is always active and protects the stomach lining.

1

COX is activated only during tissue injury and causes inflammation and pain.

2

NSAIDs inhibit COX enzymes, preventing production.

prostaglandin

The primary effects of NSAIDs include antipyretic, analgesic, and effects.

anticoagulant

Salicylates like are effective for pain, inflammation, fever, and have anticoagulant effects.

aspirin

Propionic acid derivatives are used for mild to moderate pain and __.

inflammation

Acetic acid derivatives are more effective for inflammation but carry __ side effects.

significant GI

COX2 inhibitors have a better __ profile than traditional NSAIDs.

safety

Oxicams are used for long-term management of __ and rheumatoid arthritis.

osteoarthritis

Phenomates are particularly effective for __ pain.

menstrual

Common gastrointestinal side effects of NSAIDs include dyspepsia, heartburn, and __.

abdominal pain

Signs of GI bleeding to monitor include dark tarry stools, bleeding gums, and __.

petechiae

Higher risk patients for NSAID side effects include older adults, smokers, and those with __.

pre-existing ulcers

Preventive treatments for GI side effects include proton pump inhibitors or __ antagonists.

H2 receptor

NSAIDs can impair kidney function by reducing __ to the kidneys.

blood flow

Non-aspirin NSAIDs increase the risk of __ and stroke.

heart attack

In patients experiencing dysmenorrhea, avoid __ due to the risk of heavy bleeding.

aspirin

Symptoms of salicylism include nausea, vomiting, and __ depression.

respiratory

Reye's syndrome is a rare condition requiring avoidance of aspirin in __ with viral infections.

children/adolescents

Activated charcoal is a treatment for __ toxicity.

aspirin

Glucocorticoids can amplify the risk of __ when used with NSAIDs.

stomach bleeding

Combining NSAIDs with alcohol increases __ bleeding.

stomach

Drug interactions with NSAIDs can occur with herbal supplements such as garlic and __.

ginseng

In case of kidney impairment, never use __ with advanced kidney disease.

Ketorolac

Celecoxib is a COX2 inhibitor that should be prescribed with caution in patients with __.

heart disease

IV ibuprofen should be infused slowly over __ to minimize complications.

30 minutes

Patients should discontinue aspirin one week before __ surgery.

elective

Common side effects of acetaminophen include nausea, vomiting, and __.

headaches

Patients taking acetaminophen who consume alcohol should limit their intake to __ grams per day.

2

The antidote for acetaminophen toxicity is __.

acetylcysteine