Anti-inflammatory drugs Non Steroidal (NSAIDs) and Steroidal

To eliminate the initial cause of cell injury, clear out necrotic cells, and initiate tissue repair.

(1) Non-steroid anti-inflammatory drugs (NSAIDs) (2) Steroid anti-inflammatory drugs (3) 5-LOX inhibitors and leukotriene receptor antagonists

Antipyretic, analgesic, and antiinflammatory.

Promote inflammation, pain, and fever; support blood clotting; and protect the lining of the stomach from the effects of acid.

arachidonic acid, Phospholipase A2 and Cyclooxygenase

Most are irreversible inhibitors of cyclooxygenase activity.

An enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances.

It cleaves the sn-2 acyl chain of a glycerophospholipid, releasing arachidonic acid, a fatty acid-derived lipid mediator.

prostaglandin H2 and leuktriene A4.

They catalyze a key step in the conversion of arachidonate to prostaglandin G2 (PGG2), the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases.

The primary functional difference is that prostaglandin G2 (PGG2) is the direct, unstable intermediate product of arachidonic acid oxidation, while prostaglandin H2 (PGH2) serves as the universal precursor from which all biologically active terminal prostaglandins and thromboxanes are synthesized.

platelets and gastric mucosa.

COX-2 plays a mayor role in inflammation and its production is induced during inflammation.

The Kolbe Synthesis

Antipyretic, analgesic, antiinflammatory, and anticoagulant.

Aspirin acts as an acetylating agent. It transfers its acetyl group to a specific serine residue located deep within the hydrophobic catalytic channel of the COX enzyme. In COX-1: it acetylates Ser-530 (and Ser-516 in COX-2).

Since platelets cannot synthesize new proteins, once aspirin acetylates the COX-1 enzymes of a platelet, that specific platelet is permenantly disbaled from manufacturing thromboxane A2. So the antiplatelet effect persists for the remaining lifespan of the platelet (7-10 days).

Gastrointestinal symptoms Bleeding CNS toxicity Allergic reaction Salicylate reaction (CNS reaction) Renal damage

Aspirin exhibits distinct, dose-dependent clinical effects because its affinity for its two target enzymes—cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)—varies drastically based on concentration. While low doses easily disable the hyper-sensitive COX-1 enzyme, much higher concentrations are required to overwhelm and block COX-2.

Low dose <300mg blocks platelet aggregation Intermediate: 300-2400mg/day antipyretic and analgesic effects High: 2400-4000mg/day Anti-inflammatory effects

Salicylic acid can be conjugated with glucuronic acid because its chemical structure features two distinct, highly reactive nucleophilic functional groups: a carboxylic acid group and a phenolic hydroxyl group. Because both of these functional groups can act as chemical handles, the liver’s UDP-glucuronosyltransferase (UGT) enzymes can attach glucuronic acid to either position.

Salicylic acid can be O-sulfated because it possesses a phenolic hydroxyl group ((-OH)) attached directly to its aromatic benzene ring. Sulfotransferases generally do not target carboxylic acids for sulfation. Carboxyl groups are instead heavily prioritized by the liver for glycine conjugation

Due to the hydroxyl group being a strong ortho/para director.

Because of the presence of a carboxylic acid group.