Chapter 16: Drug Therapy to Decrease Pain, Fever, and Inflammation

Prostaglandins

Prostaglandins are important chemical mediators involved in various physiological and pathological processes throughout the body.

• Definition: Prostaglandins are lipid compounds derived enzymatically from fatty acids, present in most body tissues.

• Functions:

  • Regulate many body functions, including inflammation, blood flow, and the formation of blood clots.

  • Participate in the inflammatory response, especially after cellular injury.

  • Exert diverse and sometimes opposing effects on different tissues.

• Location: Found in most body tissues, not limited to the central nervous system.

Example: Prostaglandins are released at sites of tissue injury, contributing to pain, redness, and swelling.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Mechanism of Action

NSAIDs are a class of drugs commonly used to reduce pain, fever, and inflammation by interfering with prostaglandin synthesis.

• Mechanism:

  • Inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are required for prostaglandin production.

  • Block pain impulse transmission both centrally (in the CNS) and peripherally.

  • Reduce fever by decreasing the hypothalamic response and resetting the body's "thermostat" to a lower level.

  • Some NSAIDs (e.g., aspirin) have antiplatelet effects, reducing blood clot formation.

• Acetaminophen: Not classified as an NSAID; lacks anti-inflammatory and antiplatelet properties.

Example: Ibuprofen and aspirin are NSAIDs that relieve pain and inflammation by inhibiting COX enzymes.

Body Temperature Regulation

The body maintains its temperature through a central regulating center in the brain.

• Hypothalamus: The hypothalamus acts as the body's thermostat, controlling temperature homeostasis.

• Drug Action: NSAIDs and acetaminophen reduce fever by acting on the hypothalamus.

Example: During fever, NSAIDs lower body temperature by resetting the hypothalamic set point.

Salicylates: Aspirin (Acetylsalicylic Acid, ASA)

Aspirin is a widely used salicylate with multiple therapeutic effects.

• Mechanism: Acts both centrally and peripherally to block pain transmission, reduce fever, and diminish inflammation.

• Antiplatelet Effect: Suppresses platelet aggregation, reducing the risk of blood clots.

• Indications: Low-dose aspirin is used to manage ischemic stroke, transient ischemic attack (TIA), angina, and acute myocardial infarction (MI).

Example: A patient with a history of heart attack may be prescribed low-dose aspirin to prevent recurrence.

Acetaminophen (Paracetamol)

Acetaminophen is a common analgesic and antipyretic agent, distinct from NSAIDs.

• Properties:

  • Does not cause gastrointestinal (GI) irritation, bleeding, or interfere with blood clotting.

  • Equal to aspirin in pain and fever relief, but lacks anti-inflammatory activity.

  • Metabolized in the liver; a small amount forms a toxic metabolite.

• Risks:

  • Overdose (acute or chronic) can cause severe liver damage or fatal liver necrosis.

  • Alcohol abuse increases the risk of liver toxicity, even at therapeutic doses.

• Dosage Forms: Available as tablets, liquids, and rectal suppositories.

Example: Acetaminophen is often used for headache relief in patients who cannot tolerate NSAIDs.

Acetaminophen Toxicity

• Prevention: Maximum daily dose is 4 g (4,000 mg) from all sources.

• Manifestations:

  • Early signs are nonspecific; liver function tests rise 24–48 hours after overdose.

  • Later signs include jaundice, vomiting, CNS stimulation (excitement, delirium), coma, and death.

• Treatment:

  • Gastric lavage and activated charcoal if within 4 hours of ingestion.

  • Antidote: Acetylcysteine (oral or IV), most effective within 8 hours, may help up to 36 hours post-ingestion.

  • Does not reverse existing liver damage.

Example: A patient presenting with suspected acetaminophen overdose should receive acetylcysteine as soon as possible.

Types of Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are classified based on their chemical structure and selectivity for COX enzymes.

• Propionic Acid Derivatives: Ibuprofen – inhibits prostaglandin synthesis in CNS and PNS.

• Oxicam Derivatives: Meloxicam

• Acetic Acid Derivatives: Indomethacin – strong anti-inflammatory effects, more severe adverse effects.

• Selective COX-2 Inhibitors: Celecoxib – selectively block prostaglandins involved in pain/inflammation, sparing those with protective effects on gastric mucosa, kidney, and platelets.

Example: Celecoxib is preferred in patients at risk for GI complications.

Indications for NSAID and Acetaminophen Use

NSAIDs and acetaminophen are used for a variety of conditions involving pain, fever, and inflammation.

• Inflammatory Disorders: Osteoarthritis, rheumatoid arthritis, bursitis, degenerative joint disease.

• Pain Relief: Effective for mild to moderate pain (e.g., headache, minor trauma, minor surgery).

• Fever Reduction: Both NSAIDs and acetaminophen are antipyretic; aspirin is avoided in children due to Reye syndrome risk.

• Antiplatelet Effect: Low-dose aspirin reduces risk of recurrent ischemic events (stroke, TIA, MI).

Example: Ibuprofen is commonly used for musculoskeletal pain, while acetaminophen is preferred for fever in children.

Contraindications for NSAID Use

NSAIDs are associated with several risks and are contraindicated in certain populations.

• Gastrointestinal Risks: Increased risk of GI bleeding, ulceration, and perforation.

• Contraindicated in:

  • Peptic ulcer disease

  • GI or other bleeding disorders

  • Abnormal kidney function

  • Hypersensitivity to aspirin

  • Chronic alcohol abuse

  • Children/adolescents with viral infections (due to Reye syndrome risk)

  • Pregnancy (risk of anemia, hemorrhage, fetal toxicity, premature ductus arteriosus closure, stillbirth)

Example: NSAIDs should be avoided in patients with a history of peptic ulcers or chronic kidney disease.

Antigout Medications

Gout is a metabolic disorder characterized by elevated uric acid levels, leading to joint inflammation.

• Mitotic Agent: Colchicine – treats and prevents gout by inhibiting white blood cell migration to urate crystal deposits, reducing inflammation.

• Uricosuric Agents: Allopurinol – reduces serum uric acid levels by inhibiting its production.

Example: Colchicine is used during acute gout attacks, while allopurinol is used for long-term uric acid control.

Table: Comparison of Common Analgesic and Anti-inflammatory Drugs

Additional info: This table summarizes the main properties, uses, and risks of common drugs discussed in this chapter for quick comparison.