1564845_634858061366620000

AUTOCOIDS

AUTOCOIDS By Shiva [email protected]

INTRODUCTIONNaturally occuring substances termed as local harmones which originate from diffuse tissues & produce intense pharmacological action near their site of formation & release.Autos=Self ; akos= remedy/ medicinal agent.CLASSIFICATIONBased on chemical nature;1.BIOGENIC / ENDOGENOUS AMINES: Histamine, 5-HT.2.POLYPEPTIDES:Bradykinin, sub-p.3.LIPID SOLUBLE ORGANIC ACIDS/ PHOSPHO LIPID DERIVATIVES:(A).EICOSINOIDS: PGS, PCS, LTS, TXS.(B).PAF.HISTAMINETissue amine.Histos- Tissue.DISTRIBUTION: Widely distributed in almost all mammal tissues & in venom of bees & wasps.SYNTHESIS: In mammals formed by Decarboxylation of Histidine in prescence of Histidine decarboxylase.STORAGE: Present in platelets, leucocytes, basophills & mastcells.Mainly in mastcells & basophills due to presence of his.decarboxylase, specialised storage granules. MECHANISM OF ACTIONActs through 4 receptors viz : H1, H2, H3, H4 all belonging to family GPCR.Activation of H1 receptors :Activation of H2 receptors:PHARMACOLOGICAL ACTIONSCVS: (A). BLOOD VESSELS: In herbivores Sys & Pul vasoconstriction.In humans Pul.vasodilation.Acts by 3 ways: (a).Activation of H1 receptors on the endothelial cells cause rapid- short lived vasodilation.(b).Activation of H2 receptors in the vascular smooth muscle causes slower but prolonged vasodilation.(c).Relaxation of smooth muscle of capillaries & venules leading to their dilation and fall in BP.PHARMACOLOGICAL ACTIONS(B).BP: Therapeutic doses induces hypotension, short lived.Large doses prolonged hypotension.Hypotension left untreated may cause irreversible shock & death.Histamine induced hypotension is partially reversed by anti-histaminics & completely reversed by adrenaline.PHARMACOLOGICAL ACTIONSTRIPLE RESPONSE; When given (20mcg) ID develops a triple response :(a).FLUSH(RED REACTION): Red line r spot develop with in 10sec, due to local dilation of capillaries & venules.(b).WHEAL: Local swelling due to edema, mottled reddening around injury. Lasts about 1 1/2min.Due to increased permeability of capillaries 7 post capillary venules with consequent xtravasation of fluid.PHARMACOLOGICAL ACTIONS(c).FLARE: Redness with irregular margins spreads out from injury.Triple response is part of normal reaction to injury.Its prevention is used to evaluate anti-histaminic activity of a new drug.(C).HEART:Increases sinus rate (+ve chronotropic action)Increases the amplitude of ventricular contraction (+inotropic effect)Decreases AV conduction time & increases coronary blood flow, high conc. induce ven.fibrillation.PHARMACOLOGICAL ACTIONS(D)SMOOTH MUSCLE: Stimulates smooth muscles of various tissues by direct action(H1).Bronchial & Uterine smooth muscle highly sensitive.GIT & Ureteral smooth muscle respond moderately.Thru H1 receptor gall bladder contraction ,H2 receptor gall bladder relaxation.H induced bronchospasm antagonised by adrenaline, isoprenaline & aminophylline but not by anti-histaminics r atropine.PHARMACOLOGICAL ACTIONSENDOCRINE GLANDS: Important physiological mediator of gastric acid secretion.CNS: Doesnt cross BBB, H constituted in 2types of cells Histaminergic neurones & Mast cells.Considered as Waking amine- increase in sensitivity of large cerebral areas to excitatory inputs.IMMUNOMODULATION: Increases Humoral & Cellular immunity by various receptors , H1- cellular immunity , H2- Humoral immunity. A,D,M,E:Stable compound & absorbed from all sites .Rapidly under go first pass metabolism in liver.Metabolism varies acc.to: animal spcs, sex , organ studied.Chemically it is B-Imidazolyl etylamine.End products of metabolism include N-Methyl imidazole aectic acid, N-acetyl histamine. ADRDue to pharmacological actions: hypotension, visual disturbances, dyspnea, diarrhoea.Man, Gunea pig- extremely sensitive.Rats & Mice highly resistant.Large dose causes severe nausea, gripping, headache & sweating.USES:Study of gastric acid secretion. ANTI-HISTAMINICSCertain phenolic ether anti-histaminic properties.CLASSIFICATION: By two ways Clinically & Chemically.(A).CLINICAL CLASSIFICATION:1.POTENT & SEDATIVE: Diphenhydramine, Promethazine.2.POTENT & LESS SEDATIVE: Cyclizine, Meclizine.3.LESS POTENT & LESS SEDATIVE: Antazoline, Cinnarizine.4.NON SEDATIVE: Loratidine, Cetirizine.CHEMICAL CLASSIFICATIONGeneral formula: Based on configuration of X classified as :1. ETHANOLAMINES(X=O): Diphenhydramine, Doxylamine.2.ETHYLENE DIAMINES(X=N): Mepiramine, Antazoline.(show negligible anti-cholinergic & anti-emetic efcts)3.ALKYL AMINES (X=C): Chloropheneramine, Triprolidine.4.PIPERAZINES: (X=C in conjunction with piperazine ring): Cinnarizine, Cetirizine.CHEMICAL CLASSIFICATION5.PHENO THIAZINES (X=N as apart of phenothiazine nucleus): Promethazine, Trimeprazine, show potent anti-emetic effect.6.PIPERIDINES: Loratadine, Fexofenadine.7.DIBENZOXYPINES: Doxepine (Tricyclic anti depressant) shows potent anti-histaminic properties. H- ANTAGONISTIC ACTIONS1.ANTI-HISTAMINIC ACTIONS: Competatively block H at various sites.Antgonize stimulant action of H on: Smooth muscle of GIT, bronchi, uterus & bld.ves.Reduce H induced triple response.Anti-allergic & anti-inflammatory actions involve: (a). Inhibition of release of mediators from mastcells, basophills.(b).Down regulation of H1-receptors.Dont antgonize CVS actions of H.ANTAGONISTIC ACTIONSOTHER ACTIONS: Related to their blocking of 5-HT & A1-Adreno receptors.1.SEDATION & HYPNOSIS: CNS depression common side effect.Induce varying degrees of sedation, drowsiness & sleep.2.CNS STIMULATION: Stimulation is less , conventional doses of Promethazine cause restlessness, tremors & insomnia. ANTAGONISTIC ACTIONS3. ON ANS: First gen. anti-histaminics show muscarinic blocking activity, second gen. anti-histaminics doesnt show these actions.4.ANTI-EMETIC & ANTI-MOTION SICKNESS: Diphenhydramine & Promethazine block histaminergic signals from the vestibular nucleus to vomiting center.5.ANTI-PARKINSONIAN EFFECTS: Central anti-muscarinic actions useful in treating parkinsonism.ANTAGONISTIC ACTIONS6.CVS: Rapid IV administration of Diphenhydramine, Antazoline may produce dose related prolongation of QT interval due to membrane stabilising effect.7.LOCAL ANAESTHESIA: Promethazine, Diphenhydramine exhibit local anaesthetic activity.A,D,M,E: Well absorbed orally & parenterally.Anti-histaminic effect starts with in 15-30 min, peaks by 1hr & lasts for 3-6hrs.Meclizine- action persists for 12-24hrs.ANTAGONISTIC ACTIONSA,DM,E: First gen compounds metabolised by CYP3A4 in liver.H1-antagonists induce hepatic microsomal enzymes, facilitating their own metabolism.ADR: Mild,1.CNS: Sedation & Hypnosis, Fatigue.In children less than 2yrs- Promethazine cause Apnoea.ANTI-MUSCARINIC EFFECTS: Dry mouth, blurred vision, bladder disturbances & rarely impotence.

ADR:GIT: Nausea, vomiting, epi-gastric distress.MISC: May produce allergic manifestations despite of their anti-allergic & anti-inflammatory properties.THERAPEUTIC USESUsed in treatment of : 1.Allergic disorders,2.Reagenic allergy,3. Allergic conjunctivitis ,4. Mastocytosis,5.Other uses (a).As hypnotics, (b).As anti-emetics, (c).In parkinsonism, (d).In motion sickness & vertigo, (e).Anti-tussives, (f).Local anaesthetics. THANK YOU