NSAIDs and Inflammatory Pain

• Non-steroidal anti-inflammatory drugs (NSAIDs) are non-narcotic or non-opioid analgesics.
• NSAIDs alleviate pain without interacting with opioid receptors.
• NSAIDs have analgesic, antipyretic, and anti-inflammatory effects.
• Analgesics, including NSAIDs, are frequently prescribed for dental pain.

Inflammatory Pain

• Inflammation is a complex physiological response to physical injury, infection, and allergy.
• Mediators formed during inflammation contribute to acute pain by stimulating or sensitizing primary afferent neurons.
• Pain, fever, and inflammation cause arachidonic acid to be liberated from the cell membrane's phospholipid fraction.
• Arachidonic acid is converted to prostanoids (PGs, prostacyclines "PGI2", and TXA2) via the cyclooxygenase pathway (COX-1 & COX-2).

Prostaglandins

• NSAIDs inhibit prostaglandin synthesis by inhibiting COX enzymes.
• Prostaglandins (PGs) are long-chain fatty acids found in most tissues and organs.
• Arachidonic acid is the precursor for the biosynthesis of all PGs.
• Cyclooxygenase (COX) is the enzyme involved in forming PGs from arachidonic acid.
• Main PGs in humans include prostaglandin D2 (PGD2), E2 (PGE2), F2 (PGF2), and prostacyclin (PGI-2).
• Leukotrienes, produced from arachidonic acid by lipoxygenase, play roles in asthma, glomerulonephritis, and inflammatory bowel disease.

Types and Distribution of COX Enzymes

• Cyclooxygenase (COX) enzymes are bound to the endoplasmic reticulum.
• COX enzymes exist in three isoforms: COX-1, COX-2, and COX-3.
• COX-1 is constitutive, always present, activated by normal physiological stimuli, and widely distributed.
• COX-1 participates in protecting gastric mucosa, homeostasis, and cell division.
• COX-1 is present in the GIT (stomach, intestine), kidney, blood vessels, endothelium, and platelets.
• COX-2 is induced during inflammation or pathological stimuli.
• COX-2 is present in inflammatory sites in endothelial cells, macrophages, other inflammatory cells, and blood vessels.
• COX-2 produced prostaglandins mediate pain, fever, leukocyte proliferation, and inflammation.
• COX-3 is found in the brain and spinal cord.

Effects of PGs in the Body

• Prostaglandin functions vary depending on the tissue.
• PGE-1 & 2 cause vasodilation, decreased gastric acid secretion, bronchodilation, maintenance of renal function, pain sensitization, uterine contraction, maintenance of patent ductus arteriosus, and fever.
• PGF-2 causes bronchoconstriction and increases drainage from aqueous humor.
• PGI-2 causes vasodilation, inhibits platelet aggregation, maintains patent ductus arteriosus, provides pain sensitization, and gastric cytoprotection.
• Prostacyclins (PGI-2) in the vascular wall act as dilators of blood vessels and inhibit platelet aggregation.
• TXA2 released from platelets triggers platelet aggregation.
• Elevated TXA2 levels in certain smooth muscles of the respiratory system cause bronchoconstriction.

PGs and GIT

• Prostaglandin E2, produced by the gastric mucosa, has a cytoprotective effect by inhibiting HCl secretion and stimulating mucus and bicarbonate secretion.
• Prostaglandin deficiency is thought to be involved in the pathogenesis of peptic ulcers.

Uses of PGs

• Misoprostol is a stable analog of prostaglandin E1, approved for preventing gastric ulcers induced by NSAIDs.
• Topical PGs like latanoprost and bimatoprost (PGF2 analogs) are preferred for initial therapy in open-angle glaucoma.
• Low concentrations of PGE2 and PGF2 contract the pregnant uterus.
• PGs are mainly used in mid-trimester abortion and missed abortion and for inducing labor.

Adverse Effects of PGs

• Adverse effects: Nausea, vomiting, diarrhea, fever, flushing, hypotension, backache (due to uterine contractions).
• Injections can be painful due to sensitization of nerve endings.