1 / 24

autocoids

autocoids

guest51485
Télécharger la présentation

autocoids

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. AUTOCOIDS By Shiva B.Pharmacy Shiva.pharmacist@gmail.com

  2. INTRODUCTION • Naturally occuring substances – termed as local harmones which originate from diffuse tissues & produce intense pharmacological action near their site of formation & release. • Auto’s=Self ; akos= remedy/ medicinal agent.

  3. CLASSIFICATION • Based 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: PG’S, PC’S, LT’S, TX’S. • (B).PAF.

  4. HISTAMINE • Tissue 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.

  5. MECHANISM OF ACTION • Acts through 4 receptors viz : H1, H2, H3, H4 – all belonging to family GPCR. • Activation of H1 receptors : • Activation of H2 receptors:

  6. PHARMACOLOGICAL ACTIONS • CVS: (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.

  7. 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.

  8. PHARMACOLOGICAL ACTIONS • TRIPLE 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.

  9. 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 (+vechronotropic action) • Increases the amplitude of ventricular contraction (+inotropic effect) • Decreases AV conduction time & increases coronary blood flow, high conc. induce ven.fibrillation.

  10. 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.

  11. PHARMACOLOGICAL ACTIONS • ENDOCRINE GLANDS: Important physiological mediator of gastric acid secretion. • CNS: Doesn’t cross BBB, ‘H’ constituted in 2types of cells – Histaminergicneurones & 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.

  12. 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-Imidazolyletylamine. • End products of metabolism include N-Methyl imidazoleaectic acid, N-acetyl histamine.

  13. ADR • Due 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.

  14. ANTI-HISTAMINICS • Certain 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.

  15. CHEMICAL CLASSIFICATION • General 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.

  16. CHEMICAL CLASSIFICATION • 5.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.

  17. ‘H’- ANTAGONISTIC ACTIONS • 1.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. • Don’t antgonize CVS actions of ‘H’.

  18. ANTAGONISTIC ACTIONS • OTHER 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.

  19. ANTAGONISTIC ACTIONS • 3. ON ANS: First gen. anti-histaminics show muscarinic blocking activity, second gen. anti-histaminics doesn’t 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.

  20. ANTAGONISTIC ACTIONS • 6.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.

  21. ANTAGONISTIC ACTIONS • A,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.

  22. ADR: • GIT: Nausea, vomiting, epi-gastric distress. • MISC: May produce allergic manifestations despite of their anti-allergic & anti-inflammatory properties.

  23. THERAPEUTIC USES Used 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.

  24. THANK YOU

More Related