Autacoids – Key Vocabulary

A comprehensive set of vocabulary flashcards covering autacoids, their receptors, pharmacology, therapeutic uses, adverse effects, and clinical applications, based on the lecture notes.

Autacoids

Locally acting ‘local hormones’ with heterogeneous structures and diverse pharmacologic actions.

Amines (Autacoids)

Include histamine and serotonin.

Ergot Alkaloids

Derivatives of lysergic acid obtained from ergot fungus; include ergotamine, ergometrine and semisynthetic analogues.

Vasoactive Peptides – Vasoconstrictors

Angiotensin II, vasopressin, endothelin, neuropeptide Y.

Vasoactive Peptides – Vasodilators

Bradykinin, natriuretic peptides, substance P, vasoactive intestinal peptide (VIP), neurotensin.

Eicosanoids

Fatty-acid derivatives including prostaglandins and leukotrienes.

Platelet-Activating Factor (PAF)

Potent phospholipid autacoid involved in inflammation and hemostasis.

Histamine

Biogenic amine formed from histidine; stored in mast cells & basophils; mediates inflammation, allergy and neurotransmission.

Histamine Release – Immunologic

Antigen–antibody interaction on IgE-sensitized mast cells triggers degranulation.

Histamine Release – Mechanical

Trauma or mechanical injury causes mast-cell disruption and histamine liberation.

Histamine Release – Drugs

Agents like morphine, trimethaphan, succinylcholine promote non-immune histamine release.

H1 Receptor

Located on endothelium, smooth muscle, brain; activates IP3/DAG pathway → ↑ intracellular Ca²⁺.

H2 Receptor

Found in gastric mucosa & heart; coupled to ↑ cAMP → gastric acid secretion & cardiac stimulation.

H3 Receptor

Presynaptic receptor on histaminergic neurons; decreases cAMP to modulate neurotransmitter release.

H4 Receptor

Expressed on leukocytes and bone marrow; involved in chemotaxis and inflammatory modulation.

Physiologic Histamine Antagonist

Adrenaline opposes many histamine actions via α/β receptor activation.

Mast-Cell Stabilizers

Cromolyn and nedocromil prevent histamine release by inhibiting degranulation.

First-Generation Antihistaminics

Lipid-soluble H1 blockers (e.g., diphenhydramine, chlorpheniramine) causing sedation & anticholinergic effects.

Second-Generation Antihistaminics

Less lipid-soluble H1 blockers (e.g., loratadine, cetirizine) with minimal CNS and anticholinergic effects.

Doxylamine + Pyridoxine

H1 blocker combination approved for pregnancy-induced nausea and vomiting.

Cyproheptadine

5-HT2/H1 antagonist producing weight gain, used for carcinoid tumor and cold-induced urticaria.

H1 Blocker – Adverse Effects

Sedation, dizziness, dry mouth, urinary retention, constipation, paradoxical excitation in children.

Serotonin (5-Hydroxytryptamine)

Amine synthesized from L-tryptophan; 90 % in enterochromaffin cells; precursor of melatonin.

5-HT1A Receptor

Located in CNS; modulates mood, anxiety; agonist buspirone is an anxiolytic.

5-HT1D Receptor

Found on cerebral vessels & trigeminal nerves; agonists (triptans) relieve migraine via vasoconstriction.

5-HT2 Receptor

Mediates vasoconstriction, platelet aggregation, GIT contraction; blocked by cyproheptadine and methysergide.

5-HT3 Receptor

Ligand-gated ion channel on vagal afferents & CNS CTZ; antagonists (ondansetron) prevent emesis.

5-HT4 Receptor

Enhances acetylcholine release in ENS; agonists like metoclopramide are prokinetic.

Buspirone

Partial 5-HT1A agonist used as a non-benzodiazepine anxiolytic.

Sumatriptan

Prototype 5-HT1D agonist for acute migraine; causes selective cerebral vasoconstriction.

Triptans

Class of 5-HT1D/1B agonists (e.g., zolmitriptan) first-line therapy for migraine attacks.

Ondansetron

Selective 5-HT3 antagonist used for postoperative and chemotherapy-induced vomiting.

Methysergide

Semisynthetic ergot; 5-HT2 antagonist for migraine prophylaxis; risk of retroperitoneal fibrosis.

Dexfenfluramine

5-HT2 agonist and serotonin releaser formerly used as appetite suppressant.

Ergotamine

Natural ergot alkaloid; partial α-adrenergic & 5-HT agonist; aborts migraine attack.

Ergometrine (Ergonovine)

Ergot alkaloid with potent uterine oxytocic activity; used for postpartum hemorrhage.

Dihydroergotamine

Hydrogenated ergot derivative with less vasospasm; alternative to ergotamine for migraine.

Methylergometrine

Semisynthetic derivative more potent than ergometrine; controls postpartum hemorrhage.

Ergotism

Toxicity of ergot alkaloids manifesting as cold extremities, tingling, gangrene, hypertension.

Ergotamine – Contraindications

Coronary or peripheral vascular disease, hypertension, pregnancy, liver or renal impairment.

Migraine – Aura

Prodromal neurologic symptoms (visual flashes, paresthesia) linked to intracranial vasoconstriction.

Migraine – Headache Phase

Unilateral throbbing pain with nausea due to cerebral vasodilatation.

Migraine Prophylaxis – β-Blocker

Propranolol reduces attack frequency by modulating vascular tone and CNS activity.

Flunarizine

Calcium channel blocker preventing Ca²⁺ overload in brain; used for migraine prevention.

Migraine Abortive Therapy – NSAIDs

Aspirin or paracetamol relieve mild attacks by inhibiting prostaglandin-mediated pain.

Cafergot

Combination of caffeine with ergotamine; caffeine enhances vasoconstriction and oral absorption.

Sumatriptan – Dosing Caution

Maximum two doses per attack; avoid within 24 h of ergotamine due to additive vasoconstriction.

Bradykinin

Vasodilator peptide producing pain, ↑ vascular permeability and hypotension.

Natriuretic Peptides

Endogenous peptides (ANP, BNP) causing natriuresis, vasodilatation; markers in heart failure.

Endothelins

Potent vasoconstrictor peptides implicated in pulmonary hypertension and cardiovascular disease.

Nitric Oxide (NO)

Endothelium-derived relaxing factor producing vasodilatation via cGMP; dysregulation in CV disorders.

Substance P

Neurokinin peptide mediating pain transmission and vasodilatation; target of NK1 antagonists.

Vasoactive Intestinal Peptide (VIP)

Gut neuropeptide causing smooth-muscle relaxation, vasodilatation and increased intestinal secretion.

Neurotensin

Tridecapeptide functioning in CNS and GIT; vasodilatory and analgesic roles.

Cytokines (as Autacoids)

Pleiotropic protein mediators (e.g., interleukins, TNF-α) influencing immunity and inflammation.

Clobenpropit

H3 inverse agonist explored for obesity treatment and allergic rhinitis (H4 activity).

Tiprolisant

H3 inverse agonist reducing sleepiness in narcolepsy by enhancing histaminergic neurotransmission.

Carbinoxamine

First-generation antihistamine used for allergy symptoms; notable sedative properties.

Astemizole

Second-generation antihistamine withdrawn in many markets for QT prolongation risk.

Hydroxyzine

Sedating H1 blocker with anti-anxiety and anti-pruritic properties.

Meclizine

First-generation antihistamine effective for motion sickness prophylaxis.

Metoclopramide

D2 and 5-HT4 agonist; antiemetic and prokinetic used in GERD and migraine.

Fluvoxamine

Selective serotonin reuptake inhibitor (SSRI) used for depression and OCD.

Lysergic Acid Diethylamide (LSD)

Potent hallucinogen derived from ergot alkaloids.

Bromocriptine

Ergot-derived dopamine agonist for Parkinson’s disease and hyperprolactinemia.

Alpha-Adrenoceptor Blockade (Ergotoxine)

Produces vasodilatation useful in peripheral vascular disease but may cause orthostatic hypotension.

Chemoreceptor Trigger Zone (CTZ)

Medullary area stimulated by ergots causing nausea and vomiting.

Prokinetic Drugs

Agents (e.g., itopride, metoclopramide) that increase GI motility via 5-HT4 or cholinergic mechanisms.