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OXYTOCIN

OXYTOCIN. Is synthesized in the PVN (SON) (luteal cells, endometrium, and the placental) Oxytocin-neurophysin complex Neurohypophysis, hypothalamus, brain stem, and spinal cord. OXYTOCIN. Stimuli for secretion: dilation of the cervix, vagina and from suckling at the breast

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OXYTOCIN

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  1. OXYTOCIN • Is synthesized in the PVN (SON) (luteal cells, endometrium, and the placental) • Oxytocin-neurophysin complex • Neurohypophysis, hypothalamus, brain stem, and spinal cord

  2. OXYTOCIN • Stimuli for secretion: dilation of the cervix, vagina and from suckling at the breast • Estradiol and Relaxin • Ethanol, pain, dehydration, hemorrhage and hypovolemia

  3. Physiological Roles of Oxytocin • Uterus (estrogen and progestrone) • Breast (milk ejection) • Oxytocin receptors (PG production)

  4. Clinical Use of Oxytocin • Induction of labor • Augmentation of labor • Third stage of labor and puerperium • Oxytocin challenge test • Oxytocin-receptor antagonists (Atosiban)

  5. Vasopressin and Other Agents Affecting the Renal Conservation of Water

  6. INTRODUCTION TO VASOPRESSIN • ADH • Vasopressor • Neurotransmitter • Secretion of ACTH • Regulation of CVS • Temperature • Visceral functions • Promotes the release of coagulation factors • Platelet aggregability

  7. Physiology of Vasopressin • Anatomy (hypothalamiconeurohypophyseal system, and renal collecting-duct system) • Synthesis (SON, PVN) • Parvicellular neurons • Synthesis • Transport and storage • Release

  8. Vasopressin Synthesis Outside the CNS • Heart (elevated wall stress) • Adrenal Gland (catecholamine secretion)

  9. Regulation ofVasopressin Secretion • Hyperosmolality (osmoreceptive complex) • SFO, OVLT, MnPO (Aquaporin 4) • Hepatic Portal Osmoreceptors • Hypovolemia and hypotension (baroreceptors in the left atrium, left ventricle, pulmonary veins, carotid sinus and aorta) • Pain, nausea, and hypoxia

  10. Stimulators ACh (nAChR) Histamine (H1 receptors) Dopamine (D1 and D2 receptors) Glutamine Aspartate CCK, NPY, SP, VIP, PGs, Ag ΙΙ, Ag III Inhibitors ANP GABA Opioids Modulation of Vasopressin Secretion

  11. Vincristine Cyclophosphamide TCAs Nicotine Epinephrine Morphine(HD) Lithium Ethanol Phenytoin Morphine (LD) Fluphenazine Haloperidol Promethazine Carbamazepine Pharmacological Agents of Vasopressin Secretion

  12. Basic Pharmacology of Vasopressin • Vasopressin receptors (V1a, V1b, and V2) • V1 receptors: Gq-PLC pathway • V2 receptors:Gs-AC pathway

  13. Mechanisms by which vasopressin increases the renal conservation of water

  14. NSAIDs (indomethacin) Carbamazepine Chlorpropamide Lithium (PTH) Demeclocycline Pharmacological Modifications of Antidiuretic Response to Vasopressin

  15. Nonrenal Actions of Vasopressin • Cardiovascular System • Central Nervous System (learned behaviors, depression, antipyretic factors, modulation CNS autonomic systems, and secretion of ACTH) • Blood coagulation (V2 receptors) • Contraction of uterus, GIT, platelet aggregation and glycogenolysis

  16. Vasopressin Receptor Agonists and Antagonists • Arginine vasopressin (AVP) • Desmopressin (DDAVP) • Mozavaptan • Telipressin (Glypressin)

  17. Vasopressin Receptor Agonists And Antagonists

  18. Diseases Affecting the Vasopressin system • Diabetes Insipidus (DI) Central DI Nephrogenic DI • SIADH ( lethargy, anorexia, nausea, vomiting, muscle cramp, coma, convulsions, and death)

  19. Post operative ileus Dispel intestinal gas Esophageal varices Portal hypertension Reduce bleeding during acute hemorrhagic gastritis Burn wound excision cyclophosphade-induced hemorrhagic cystitis Liver transplantation Cesarean section Uterine myoma resection Vasodilatory shock Asystole Clinical Summary: Pharmacology of Vasopressin PeptidesV1 receptor-mediated therapeutic applications

  20. ‍Clinical Summary: Pharmacology of Vasopressin Peptides • V2 receptor-mediated therapeutic applications • Water conservation • Release of blood coagulation factors (type I vWB, type IIn vWB, factor VIII, uremia and cirrhosis) • Primary nocturnal enuresis • Relieve post-lumbar puncture headache

  21. Toxicity, Adverse Effects, Contraindications, and Drug Interactions • Marked facial pallor • Increased intestinal activity • Coronary circulation (CAD) • Water intoxication • Acute renal failure • Angina, hypertension, and heart failure • Primary or psychogenic polydipsia • Allergic reactions • Local adverse effects

  22. Future Directions in Vasopressin Analogues V1a selective antagonists • Dysmenorrhea • Preterm Labor • Raynoud’s syndrome

  23. Future Directions in Vasopressin Analogues V1b selective antagonists • Stress-related disorders • Anxiety • Depression • ACTH-secreting tumors • Cushing’s syndrome

  24. Heart failure SIADH Cirrhosis Hyponatremia Brain edema Nephrotic syndrome Diabetic nephropathy Glucoma Future Directions in Vasopressin AnaloguesV2 selective antagonists

  25. Future Directions in Vasopressin AnaloguesV2 selective agonists • Central DI • Nocturnal enuresis • Nocturnal polyuria • Urinary incontinence

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