AUTOCOIDS
BY Mohammed Q. Mal-Allah Department of Pharmacology College of Medicine*
Definition: Auto = self Coids = Remedy or some times called Local Hormones Why are they very important?
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Classifications: A. Amine Autociods: 1. Histamine 2. Serotonin B. Eicosanoids (PGs; Thromboxane ; Leukotriens) C. Peptides Autociods: 1)Kinins 2) Renin; Angiotensins etc) 4. Endogenous peptides (Kinins; Renin; Angiotensins etc)
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Serotonin
Definition and Location: it is a neurotransmitter found in enterochromaffin cells in GIT (90%) , and in plateletes and in raphe nuclei of brain stem. Is serotonin as important as N.E or Histamine?*
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Mechanism of action : Interacts with 12 receptor subtypes Why is 5-HT3 receptor differs from other 5- HT receptors?
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Pharmacological actions of Serotonin
CVS: 1) Blood vessels: Potent and direct contractions on smooth muscle (via 5- HT2 ) EXCEPT : Skeletal Muscles and Heart blood vessels. Note : 5- HT can give rise to triple action: Decrease BP due to chemoreceptor response then increase BP due to Vasoconstriction (5-HT2), then decrease B.P due to skeletal muscle V.D 2) Platelet: Increase platelet aggregation via 5-HT2*
GIT: 1) increase contraction of smooth muscle (via 5- HT4 stimulated the release of ACH). What is the clinical significant? 2) Nausea and vomiting (via 5-HT3) therefore 5-HT3 antagonists are used for RX of ? Respiration : 5-HT may produce weak bronchoconstriction. CNS: very important.(Appetite; depression and mania; Pain; Anxiety; Schizophrenia).
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Clinical Uses of Serotonergic Drugs: Note1: Unlike NE or DA, serotonin its self has no clinical uses, however, its agonists and antagonists have very important therapeutic applications. Note 2: Unlike histamine where only its antagonists are used, serotonin agonists and antagonists can be used.
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Clin. Uses of Serotonergic Agonists:
1) Buspirone: 5-HT1A agonist used as anxiolytic agent. 2) Sumatriptan: 5-HT1D agonist for migraine (Treatment and prophylactic). 3) Metoclopromide (Plasil): 5-HT4 agonist as prokinetic agent (for Rx of gastroesophagial reflex). And also used for N/V via 5-HT3 antagonistic action. 4) Dexfenfuramine: Acts by stim. Release and inhib. Reuptake of serotonin. Used as anorexic agent. What is the effect of serotonin antagonists on appetite?
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Clinical Uses of Serotonergic Antagonists:
1) Ondansetron & Granisetron: 5-HT3 antagonists Common used for Rx of N/V induced by cytotoxic (chemotherapy) drugs. 2) Cyproheptadine: Both H1, 5-HT1,2 and cholinergic antagonist used for Rx carcinoid tumor (significant increases in serotonin) and to increase appetite.. 3) Ketanserin: 5-HT2/1c antagonist and a1-adrenergic blocker. (used as antihypertensive agent) 4) Methysergide: This is an ergot alkaloid acts as 5-HT1,2 antagonist used for Rx of migraine.*
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C. Vasoactive Peptides
A. Vasoconstrictors (angiotensin II; vasopressin; endothelins and neuropeptide Y. B. Vasodilators (Bradykinin and related Kinins; Natriuretic Pepties; Vasoactive Intestinal Peptide; substance P; Neurotensin)*
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Vasodialtion may be due to:
I. A direct inhibitory effect of kinins on the arteriolar smooth m. II. May be mediated by the release of vasodilator PGS(E2 & I2).*
b. The predominant effect of kinins on veins is contraction & may be due to: 1-direct stimulation of venous smooth m .. or 2- due to the release of vasoconstrictor PGs(F2 α). *
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