AUTOCOIDS. Mr. D.Raju, M.pharm, Lecturer
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1 AUTOCOIDS Mr. D.Raju, M.pharm, Lecturer
2 DEFINITION An organic substance, such as a hormone, produced in one part of organism and transported by the blood or lymph to another part of the organism where it exerts a physiologic effect on that part.
3 TYPES OF AUTACOIDS: Amines : Histamine,5-Hydroxytryptamine. Lipids : Prostaglandins, Leukotriens, Platelet activating factor. Peptide : Bradykinin, angiotensin.
4 HISTAMINE SYNTHESIS AND DEGRADATION OF HISTAMINE Histidine decarboxylase Histamine Imadazole acetic acid N-methyl histamine N-methyl transferase oxidase Methyl imidazole acetic acid
5 PHARMACOLOGY S.M - contraction H1 H2 H3 Gastric gland-acid secretions Brain- inhibition of histamine release- sedation B.V vaso dilation B.V-dilation B.V - vaso dilatation Afferent nerve ending - stimulation Heart-postive inotropy Skin, gastric, mucosadecrease histamine release Ganglionic cell- stimulation Uterus - relaxation Lungs, spleen decrease histamine release Adrenal medulla-release of CAs Brain - transmitte
6 CLASSIFICATION H1 H2 H3 SELECTIVE AGONISTS 2- methylhistamine,2- pyridylethylamine,2- thiazolyl ethylamine 4-methy histamine, Dimaprit, impromidine ἀ-methyl histamine SELECTIVE ANTAGONISTS Mepyramine, chlorpheniramine Cimetidine, ranitidine Thioperamide, impromidine RECEPTOR TYPE G-Protein coupled G-P G-P EFFECTOR PATHWAY IP3/DAG Ca+ release C-AMP inc Ca+ infulx,k+ channel activation, camp dec
7 THERAPEUTIC INDICATION Common cold Motion sickess Duodenal ulcer(zollinger - ellision syndrome) Parkinsonism Allergic disorders Sedative and hypnotic, Anxiolytic ADR: CNS depression, fatigue, gynecomastia in men, galactorrhea women.
8 SEROTONIN Sertonin (vasoconstrictor) appeared serum. SYNTHESIS TRYPTOPHAN hydroxylase 5-Hydroxytryptophan decarboxylase 5-HT (MAO) 5-Hydroxy indole acetic acid dehydrogenase 5-Hydroxy tryptohol
9 TYPES RECEPTOR LOCATION MAIN EFFECTS 1A CNS Neuronal inhibition, Behavioural effects 1B 1D 2A 2B CNS VASCULAR- S.M CNS B.V CNS PNS S.M PLATELETS GASTRIC FUNDUS Pulmonary vasoconstrion Cerebral vaso constriction, locomotion s.m contraction SECOND MESSENGER camp camp camp IP3/DAG AGONISTS 5-CT 8-OH-DPAT Buspirone 5-CT Ergotamine 5-CT Sumatriptan ἀ-me-5-ht LSD(CNS) LSD(Peripher y) contraction IP3/DAG ἀ-me-5-ht - ANTAGONIST S Spiperone, Methiothepin, Ergotamine Methiothepin Methiothepin Ergotamine KETANSERIN, cyproheptadi ne CNS Cerebrospinal IP3/DAG ἀ-me-5-ht Methysergide
10 RECEPTOR LOCATION MAIN EFFECTS SECOND MESSENGE R AGONISTS ANTAGONI STS 5-HT3 PNS CNS Neuronal excitation, emesis ligand-gated cation channel 2-Me-5-HT, Chlorophenyl biguanide Ondansetr on,tropiset ron 5-HT4 PNS CNS Gi motility camp 5-methoxytryptamine, metochlopromide Various exp.comp 5-HT5 CNS Not known Not known Not known Not known 5-HT6 CNS Not known Not known Not known Not known 5-HT7 CNS, GI TRACT, B.V Not known camp 5-CT,LSD Various 5- HT2
11 PHARMACOLOGY CVS : Arteries are constricted as well as dilated by direct action of 5-HT. S.M : Stimualtor of GIT. GLANDS : It inhibits gastric secretion. It ulcer protective property. RESPIRATION: Hyperventilation PLATELETS : 5-HT cause change in shape of platelets and is a weak aggregator.
12 THERAPEUTIC USES 5-HT AGONISTS : Anxiolytics ( Buspirone), Depression( Fluoxetine) Migraine(Ergot alkaloids) 5-HT ANTAGONISTS: Nausea, emesis, antineoplastic therapy (Ondansetron, Granisetron, Dolasetron) ADR: Abdominal pain, Muscle cramps, Chest pain.
13 PROSTAGANDINS AND LEUKOTRIENES (EICOSANOIDS)
14 PHARMACOLOGICAL ACTIONS ORGAN PGE2 PGF2ἀ PGI2 TXA2 B.V Vaso dilatation Vaso dilatation Vaso dilatation Vaso constriction HEART Weak inotropic, cardiac stimulation Weak inotropic PLATELETS Variable effect _ Anti aggregatory aggregation UTERUS contraction contraction BRONCHI Dilatation, inhibits histamine constriction Dilatation, inhibits histamine constriction STOMACH Acid secretion(dec), Mucous production(inc) _ Acid secretion(dec), Mucous production(inc) _
15 THERAPEUTIC USES PGE1 : CHF (Alprostadil) NSAID-induced GI ulcer (misoprostol) PGF2ἀ : Topically to lower intraocular pressure in glaucoma. PGI : pulmonary hypertension.(flolan) ADR : Diarrhea, Hypotension, Flushing, Cardiac Arrest, Anemia, Menstrual irregularities, Abortion Decreased renal function.
16 LEUKOTRIENES PHARMACOLOGY : CNS : fall in B.P S.M : Bronchoconstrictors and spastic contraction of GIT at low concentration AFFERENT : Carrying pain impulses and tenderness to inflammation.
17 THERPEUTIC USES TREATMENT OF ASTHMA (Zileuton) Reduced bronchospasm ADR : GI upset, liver dysfunction
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