General Properties of Autacoids, Eicosanoids, and Histamine Pharmacology

Vocabulary practice flashcards covering autacoids, prostaglandin synthesis, COX isoforms and inhibitors, leukotriene pathways, and histamine pharmacology.

Autacoids

A group of hormone-like substances derived from local tissues that produce their biological actions at the site of release, modulating the activity of smooth muscles, glands, nerves, and platelets.

Arachidonic Acid

A $20$-carbon polyunsaturated fatty acid ($5,8,11,14$-eicosatetraenoic acid) cleaved from membrane phospholipids by phospholipase $A_2$ that serves as the principal precursor for prostaglandins, thromboxanes, and leukotrienes.

Cyclooxygenase (COX)

A membrane-bound enzyme in the endoplasmic reticulum that catalyzes the oxidation and cyclization of arachidonic acid; it acts as a 'suicide enzyme' capable of self-catalyzed destruction to switch off prostaglandin synthesis.

COX-1

The constitutive isoform of cyclooxygenase responsible for physiological housekeeping functions, including maintaining gastrointestinal mucosal integrity, mediating platelet aggregation, and supporting renal function.

COX-2

The inducible isoform of cyclooxygenase synthesized in inflammatory cells such as macrophages, leukocytes, and fibroblasts in response to pathological inflammatory stimuli.

Annexins

Glucocorticosteroid-induced proteins that inhibit phospholipase $A_2$ activity, thereby indirectly reducing the synthesis of all eicosanoid classes including prostaglandins, thromboxanes, and leukotrienes.

Coxibs

Selective COX-2 inhibitors—including celecoxib, rofecoxib, and valdecoxib—that deliver anti-inflammatory and analgesic efficacy with reduced ulcerogenic potential, but carry risks of infertility and prothrombotic cardiovascular events.

Celecoxib

A selective COX-2 inhibitor containing a pyrazole ring, a sulfonamide group, and a $CF_3$ substituent, engineered to treat pain and inflammation while sparing COX-1-dependent gastric mucosa.

Alprostadil

A synthetic prostaglandin $E_1$ ($PGE_1$) preparation used to maintain the patency of patent ductus arteriosus in neonates and administered intracavernosally or as a urethral suppository to treat erectile dysfunction.

Latanoprost

A stable, long-acting prostaglandin $F_{2\alpha}$ ($PGF_{2\alpha}$) derivative used topically to treat glaucoma by lowering intraocular pressure.

Thromboxane $A_2$ ($TXA_2$)

An arachidonic acid derivative formed in platelets by thromboxane synthase that induces potent vasoconstriction and platelet aggregation.

Prostacyclin ($PGI_2$)

An endothelial autacoid synthesized from $PGH_2$ by prostacyclin synthase that promotes vasodilation and inhibits platelet aggregation, counterbalancing thromboxane $A_2$.

Slow-Reacting Substance of Anaphylaxis (SRS-A)

A mixture of cysteinyl leukotrienes ($LTC_4$, $LTD_4$, and $LTE_4$) produced via the 5-lipoxygenase pathway that acts as a potent bronchoconstrictor during asthma and anaphylactic shock.

Leukotriene $B_4$ ($LTB_4$)

A dihydroxy leukotriene generated from $LTA_4$ via 5-lipoxygenase that primarily stimulates chemotaxis in leukocytes and spleen cells via B-LT receptors.

$CysLT_1$ Receptor Antagonists

Competitive antagonists including montelukast and zafirlukast that block cysteinyl leukotriene receptors on bronchial smooth muscle to prevent leukotriene-induced bronchoconstriction in bronchial asthma.

Epoxyeicosatrienoic Acids (EETs)

Arachidonic acid metabolites synthesized by microsomal cytochrome P450 mono-oxygenases that act on smooth muscle cells and play vital roles in cellular signaling and renal function.

Isoprostanes

Prostaglandin isomers generated non-enzymatically from arachidonic acid independent of cyclooxygenase, exerting potent vasoconstrictor effects on renal vasculature and contributing to hepatorenal syndrome.

Histamine Synthesis and Catabolism

The metabolic pathway where histidine undergoes decarboxylation to form histamine, which is subsequently converted to methyl imidazole acetic acid via N-methyl transferase or imidazole acetic acid via diamine oxidase.

Systemic Mastocytosis

A condition characterized by abnormal mast cell accumulation and hypersecretion of histamine, diagnosed by measuring elevated levels of histamine metabolites in the urine.

$H_1$ Histamine Receptor

A $G_q$-protein-coupled receptor that triggers bronchoconstriction, increased vascular permeability, endothelial contraction, pain, and itching in allergic and type I hypersensitivity reactions.

$H_2$ Histamine Receptor

A $G_s$-protein-coupled receptor found on gastric parietal cells that stimulates gastric acid secretion and mediates negative feedback on mast cells to reduce histamine release through elevated intracellular cAMP.

Hydroxyzine

A first-generation $H_1$-receptor antagonist with anxiolytic, antiemetic, antimuscarinic, and spasmolytic activities, commonly prescribed for allergic pruritus and urticaria.

Terfenadine

A second-generation $H_1$-antihistamine associated with lethal ventricular arrhythmias (torsades de pointes) via cardiac potassium channel blockade when co-administered with CYP3A4 inhibitors like ketoconazole, itraconazole, or grapefruit juice.

Cimetidine

The prototype $H_2$-receptor antagonist that suppresses basal and stimulated gastric acid production, known for significant drug-drug interactions due to cytochrome P450 inhibition and adverse anti-androgenic effects.

Ranitidine

A second-generation $H_2$-receptor antagonist prescribed for peptic ulcers and gastroesophageal reflux disease that produces fewer drug interactions than cimetidine because it does not significantly inhibit cytochrome P450.

Mast Cell Stabilizers

Agents including cromoglycate (cromolyn), nedocromil, and ketotifen that prevent transmembrane calcium ion influx induced by antigen-IgE interactions, thereby blocking degranulation and histamine release in asthma management.