This document discusses autacoids including histamine, serotonin, prostaglandins, leukotrienes, and kinins.
It describes their biosynthesis, receptors, effects, and relevant drugs. Histamine is synthesized from histidine and acts on H1, H2, and H3 receptors. Serotonin is synthesized from tryptophan and acts on multiple receptor subtypes. Prostaglandins are synthesized from arachidonic acid and have diverse vascular, bronchial, and gastrointestinal effects. Kinins are released from precursors by enzymes and cause vasodilation, pain, and inflammation by activating B1 and B2 receptors. Relevant agonists and antagonists are discussed for each autacoid system
This document discusses autacoids including histamine, serotonin, prostaglandins, leukotrienes, and kinins.
It describes their biosynthesis, receptors, effects, and relevant drugs. Histamine is synthesized from histidine and acts on H1, H2, and H3 receptors. Serotonin is synthesized from tryptophan and acts on multiple receptor subtypes. Prostaglandins are synthesized from arachidonic acid and have diverse vascular, bronchial, and gastrointestinal effects. Kinins are released from precursors by enzymes and cause vasodilation, pain, and inflammation by activating B1 and B2 receptors. Relevant agonists and antagonists are discussed for each autacoid system
This document discusses autacoids including histamine, serotonin, prostaglandins, leukotrienes, and kinins.
It describes their biosynthesis, receptors, effects, and relevant drugs. Histamine is synthesized from histidine and acts on H1, H2, and H3 receptors. Serotonin is synthesized from tryptophan and acts on multiple receptor subtypes. Prostaglandins are synthesized from arachidonic acid and have diverse vascular, bronchial, and gastrointestinal effects. Kinins are released from precursors by enzymes and cause vasodilation, pain, and inflammation by activating B1 and B2 receptors. Relevant agonists and antagonists are discussed for each autacoid system
This document discusses autacoids including histamine, serotonin, prostaglandins, leukotrienes, and kinins.
It describes their biosynthesis, receptors, effects, and relevant drugs. Histamine is synthesized from histidine and acts on H1, H2, and H3 receptors. Serotonin is synthesized from tryptophan and acts on multiple receptor subtypes. Prostaglandins are synthesized from arachidonic acid and have diverse vascular, bronchial, and gastrointestinal effects. Kinins are released from precursors by enzymes and cause vasodilation, pain, and inflammation by activating B1 and B2 receptors. Relevant agonists and antagonists are discussed for each autacoid system
b) Basophils c) Brain d) ECF-like cells of stomach 2. Steps L-histidine decarboxylase Histamine RECEPTORS AND EFFECTS A. H1 Receptor Location: • Vascular SM • Extravascular SM (Bronchi and GIT) • Endothelial cells • Sensory Nerve Endings • Brain RECEPTORS AND EFFECTS B. H2 receptor Location: • Gastric glands (Parietal Cells) • Mast cells RECEPTORS AND EFFECTS C. H3 receptor Location: • Pre-synaptic TRIPLE RESPONSE OF LEWIS 1. Erthyma/Redness 2. Spreading of erythema/redness 3. Swelling DRUGS AGONIST • Histamine Historical/Obsolete: Diagnostic Agent (Pulmonary Function Test/PFT) Quantify/determine gastric acid secretion (in work up of achlorhydria) • Betahistine (Serc) — MOA: Partial H1 agonist and H3 antagonist (central action) — Causes middle ear vasodilation leading to resorption of an endolymph ANTAGONIST • Epinephrine (Physiologic) 1. H1 Antihistamine Classical/Sedating ▪EFFECTS: a) Sedative/Hypnotic b) Anticholinergic ▪EXAMPLES: a) Ethanolamines (Diphenhydramine,Dimenhydrinate,Carbinoxamine,Doxylamine) i. Diphenhydramine (IV) ▪ Anti-allergy ▪ Sleeping Aid ▪ Centrally-acting Anticholinergic ii. Doxylamine (PO) ▪ Sleeping Aid b. Ethylenediamines • Pyrilamine,Trifelennamine -Anti-allergy c. Piperazines • Hydroxyzine (Iterax) – Anti-allergy, Allergic Rhinitis • Cyclizine, Meclizine (Bonamine) – Anti motion sickness d. Alkylamines • Bromphenamine, Chlorpheniramine – component of “Cold Tablets” e. Phenothiazines • Promethazine (Phenergan) – Anesthetic Adjunct f. Piperidine • Cyproheptadine- Management of Serotonin Syndrome NEW GENERATION 1. Piperazines (Less Sedating) • Cetirizine, Levocetirizine 2. Piperidines (True Non-Sedating) • Loratadine, Desloratadine, Fexofenadine • Only antihistamine that can be used by pilots H1 Antagonist H1 Antagonist H2 Antihistamines a) Ranitidine,Famotidine,Nizatadine,Cimetidine ▬USES: ▬ Adjuncts or Alternatives for management of acid peptic disease and GERD ▬ Adjunct anti-allergy medication ▬ADVERSE EFFECTS: ▬ CIMETIDINE: ▪ Significant Enzyme Inhibitor ▪ Anti androgenic o MALE: Gynecomastia, Loss of Libido, Sterility o FEMALE: Infertility, Loss of Libido H2 Antihistamines (H2 Blockers) • BIOSYNTHESIS Location : Enterochromaffin cells (>90%), stomach, platelet, Brain Steps: Tryptophan hydroxylase decarboxylase 5-hydroxytryptamine (5HT) • RECEPTORS I. SUMMARY OF EFFECTS a) Central (mood modulation, blood pressure regulation, temperature regulation, pain perception, vomiting) b) Peripheral (Vasoconstriction) SEROTONIN II. RECEPTORS a) 5HTA (CNS: pre –decrease release of 5HT ; post- vasoconstriction) b) 5HT2A (Smooth muscles : Contraction) c) 5HT1B/1D (Smooth muscles : Contraction) d) 5HT3 (Area postrema: Chemoreceptor trigger zone) e) 5HT4 (GIT) ANS QUIZ: If you have scanned up until here please write on your answer 41-50. AUTACOID DRUGS 5HT4 5HT3 • Tegaserod (Cisapride) • Ondansetron, Granisetron,Tropisetron,Palonosetron (Antagonist) • Agonist • USES: • USE: Management of Irritable Bowel Movement — Management of chemotherapy-induced • ROUTE: — PO, IV
5-HT1B/1D 5-HT1A • Sumatriptan,Maratriptan,Zolmitriptan (Agonists) • Buspirone (Anxiolytic) • ROUTE: • Partial Agonist in the brain — All : PO — Sumatriptan: PO,SC and Intranasal — Least Bioavailable: Sumatriptan 5-HT 2A — Most Bioavailable: Naratriptan • Ergots: Ergotamine, Dihydroxyergotamine (DHE) • DURATION: 2-3 hours (except NARATRIPTAN = 6hrs) • Partial Agonists • METABOLISM: MAO (except NARATRIPTAN= CYP) • ROUTE: • USES: — Ergotamine : PO, SL, Rectal — Management of Acute Migraine Headache — DHE: PO,IV,SC,IN (Advantage: Less Nausea) — Management of Cluster headache • USES: • ADVERSE EFFECTS: — Management of Acute Migraine Headache (Limit dose <2/week due to — Coronary Vasospasm (C/I: Coronary Artery Disease) rebound headache) — Paresthesia — Management cluster headache (NOTE: Ergotamine + Caffeine to — Pain improve oral bioavailability) — Increased BP • ADVERSE EFFECT: — SUMATRIPTAN (IN) : Nausea and Taste Perception — Ergotism — Retroperitoneal fibrosis EICOSANOID S EFFECTS: A. VASCULAR SMOOTH MUSCLES • Vasodilation : PGI2, PGE • Vasoconstriction: TXA2,PGF2 B. BRONCHIAL SMOOTH MUSCLE • Bronchodilation: PGI2, PGE • Bronchodilation: PGF2 , LTC4,LTD4 C. PLATELETS • Inhibit Aggregation: PGI2, PGE • Promote Aggregation:TXA2 D. CYTOPROTECTION (Production of Mucus in the Stomach) : PGE E. UTERINE CONTRACTION AND DYSMENORRHEA : PGF2 ,PGE F. INTRAOCULAR PRESSURE (IOP) : PGF2 , PGE DRUGS. . . . . a) Alprostadil • PGE1 analogue • EFFECT: Vasodilation • USE: Management of erectile dysfunction • ROUTE: Intracavenous injection b) Misoprostol • PGE1 analogue • Abortifacient • EFFECT: Cytoprotection • USES: Alternative in management of NSAID-induced erosive gastritis c) Epoprostinol • PGI1 analogue • EFFECT: Vasodilation • USES: — Symptomatic management of Primary Pulmonary HTN — Develops among young women with long term use of anorexiants — Irreversible condition ; px dies within 2 years KINNINS BIOSYNTHESIS 3 KININS 1. Bradykinin • Released by plasma kallikrein ; predominant in plasma 2. Lysylbradykinin (Kallidin) • Released by tissue kallikrein; predominant in urine 3. Methionyllysylbradykinin • Released by pepsin and pepsin like enzymes EFFECTS a) Cardiovascular • Arteriolar dilation (Inhibit arteriolar SM or NO release/PGE2 and PGI2) • Rapid but brief decrease BP (IV) • Venous contraction (stimulate venous SM or release of PGF2 ) b) Endocrine and Exocrine Glands • Modulator/Regulators • Activate prohormones (proinsulin, prorenin) c) Pain and Inflammation • Redness, local heat, swelling and pain RECEPTORS a) B1 • Inflammation, Collagen synthesis, cell multiplication b) B2 • Calcium mobilization • Cl- transport • NO formation • Phospholipase C & A2 & adenylyl cyclase METABOLISM a) Kininase I • Synthesized in the liver b) Kininase II • Plasma and vascular endothelial cells • Identical to ACE • Inactivation of kinins by cleaving the carboxyl terminal dipeptide phenylalanylarginine DRUGS
• B2 Antagonists 1. Icatibant — Selective B2 antagonist (2nd generation) administered subcutaneously — Blocks effects of kinins on pain, hyperalgesia, inflammation; for hereditary angioedema • Kinin synthesis Inhibitor/Kallikrein Inhibitors 1. Aprotinin 2. Ecallantide — Recombinant Plasma Kallikrein — For hereditary angioedema NOTES •Aspirin — Prostaglandin Synthesis Inhibitor — Blocks PG mediated effects of kinins •ACE Inhibitors — Enhance actions of kinins by inhibiting bradykinin metabolism
