Pain and Anti-Inflammatory Agents: Expanded Physiology and Mechanism of Action

Vocabulary practice flashcards covering physiological pathways of pain, inflammation, arachidonic acid mediators, NSAIDs, acetaminophen, corticosteroids, antigout therapies, and opioid pharmacology.

Inflammation

A coordinated protective response to tissue damage, infection, or irritation whose purpose is to contain the threat, recruit immune defenses, remove damaged material, and start tissue repair.

Transduction

The initial stage of pain processing in which potentially damaging heat, pressure, chemicals, or tissue injury activate peripheral nociceptors.

Transmission

The propagation of electrical pain signals from peripheral nociceptors through peripheral nerves to the spinal cord and onward along pathways to the brain.

Perception

The process by which brain networks interpret incoming nociceptive signals as pain, integrating them with attention, emotion, memory, and context.

Modulation

The process through which spinal cord and brain pathways amplify or dampen incoming pain signals using endogenous substances such as endorphins and enkephalins.

Rubor (Redness)

A classic sign of local inflammation caused by vasodilation of small blood vessels that increases local blood flow to the injured area.

Calor (Heat)

A classic sign of inflammation resulting from increased local blood flow and elevated local inflammatory activity.

Tumor (Swelling)

A cardinal sign of inflammation caused by increased capillary permeability, allowing fluid and immune proteins to leave the vasculature and enter tissue.

Dolor (Pain)

A cardinal sign of inflammation triggered when chemical mediators like bradykinin and prostaglandins activate or sensitize nociceptors, often augmented by tissue swelling pressure.

$\text{PGE}_2$ (Prostaglandin $\text{E}_2$)

A lipid mediator derived from arachidonic acid that contributes to nociceptor sensitization and fever, while also supporting gastric mucosal defense and renal blood-flow regulation.

$\text{PGI}_2$ (Prostacyclin)

A prostanoid synthesized primarily by vascular endothelium that promotes vasodilation and generally inhibits platelet aggregation.

$\text{TXA}_2$ (Thromboxane $\text{A}_2$)

A mediator synthesized by platelets that promotes platelet aggregation and local vasoconstriction to facilitate hemostatic plug formation after vessel injury.

COX-1

A constitutively active cyclooxygenase enzyme present in many tissues that contributes to gastric mucosal protection, platelet $\text{TXA}_2$ production, and baseline renal functions.

COX-2

A cyclooxygenase enzyme predominantly induced at sites of inflammation that produces inflammatory prostaglandins, while also serving constitutive roles in kidney and vascular physiology.

Aspirin (ASA)

An anti-inflammatory and analgesic agent that irreversibly acetylates platelet COX-1, permanently inhibiting $\text{TXA}_2$ synthesis for the entire lifespan of the affected platelet.

Reye Syndrome

A serious clinical condition linked to the administration of aspirin in children and teenagers recovering from viral illnesses.

Ketorolac

A potent NSAID analgesic indicated strictly for short-term pain management due to high risks of gastrointestinal ulceration, bleeding, and renal impairment.

Celecoxib

A selective COX-2 inhibitor designed to reduce inflammatory prostaglandins with less platelet COX-1 inhibition, though it still carries renal, blood pressure, and cardiovascular risks.

Salicylate Toxicity

A toxic syndrome whose early manifestations include tinnitus, dizziness, nausea, vomiting, and hyperventilation, which can progress to severe acid-base and metabolic disturbances.

Acetaminophen

An analgesic and antipyretic drug that acts primarily through central pain pathways and hypothalamic fever mechanisms, possessing weak peripheral anti-inflammatory activity.

NAPQI

A toxic reactive intermediate of acetaminophen metabolism that is normally detoxified by glutathione, but accumulates in overdose states to cause severe hepatotoxicity.

Acetylcysteine (N-acetylcysteine)

The specific antidote administered in acetaminophen overdose that restores hepatic glutathione reserves to neutralize the toxic metabolite NAPQI.

Corticosteroids

Agents such as prednisone and dexamethasone that bind intracellular glucocorticoid receptors to alter gene transcription, suppressing upstream inflammatory signaling and cytokine production.

Xanthine Oxidase

The metabolic enzyme that converts hypoxanthine and xanthine into uric acid during the breakdown of purines.

Colchicine

An antigout drug that disrupts neutrophil microtubule function, dampening neutrophil motility and crystal-induced joint inflammation without lowering serum urate levels.

Allopurinol

A long-term antigout medication that lowers serum urate levels over time by inhibiting the enzyme xanthine oxidase.

Probenecid

A uricosuric agent that lowers serum urate by inhibiting renal tubular urate reabsorption, thereby increasing urinary excretion of uric acid.

Endogenous Opioid Peptides

Naturally produced peptides, such as endorphins and enkephalins, that bind inhibitory G-protein-coupled opioid receptors (mu, kappa, delta) to modulate pain signaling.

Opioid Receptor Mechanism of Action

Activation of inhibitory G-protein-coupled receptors that decreases presynaptic calcium influx and increases postsynaptic potassium efflux, inhibiting neurotransmitter release and neuronal firing.

Tramadol

An opioid-like analgesic that binds opioid receptors while also inhibiting serotonin and norepinephrine reuptake, carrying risks of seizures and serotonin syndrome.

Meperidine

An opioid analgesic whose active metabolite, normeperidine, can accumulate with repeated dosing or impaired renal clearance, increasing the risk of neurotoxicity and seizures.

Naloxone

A competitive opioid receptor antagonist used to rapidly reverse opioid-induced respiratory depression and central nervous system sedation.