OXYTOCIN

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OXYTOCIN

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

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OXYTOCIN

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

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Physiological Roles of Oxytocin

• Uterus (estrogen and progestrone)
• Breast (milk ejection)
• Oxytocin receptors (PG production)

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Clinical Use of Oxytocin

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

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Vasopressin and Other Agents Affecting the Renal
Conservation of Water
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INTRODUCTION TO VASOPRESSIN

• ADH
• Vasopressor
• Neurotransmitter
• Secretion of ACTH
• Regulation of CVS
• Temperature
• Visceral functions
• Promotes the release of coagulation factors
• Platelet aggregability

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Physiology of Vasopressin

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

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Vasopressin Synthesis Outside the CNS

• Heart (elevated wall stress)
• Adrenal Gland (catecholamine secretion)

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Regulation of Vasopressin 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

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Modulation of Vasopressin Secretion

• Stimulators
• ACh (nAChR)
• Histamine (H1 receptors)
• Dopamine (D1 and D2 receptors)
• Glutamine
• Aspartate
• CCK, NPY, SP, VIP, PGs, Ag ??, Ag III

• Inhibitors
• ANP
• GABA
• Opioids

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Pharmacological Agents of Vasopressin Secretion

• Vincristine
• Cyclophosphamide
• TCAs
• Nicotine
• Epinephrine
• Morphine (HD)
• Lithium

• Ethanol
• Phenytoin
• Morphine (LD)
• Fluphenazine
• Haloperidol
• Promethazine
• Carbamazepine

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Basic Pharmacology of Vasopressin

• Vasopressin receptors (V1a, V1b, and V2)
• V1 receptors Gq-PLC pathway
• V2 receptors Gs-AC pathway

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Mechanisms by which vasopressin increases the
renal conservation of water
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Pharmacological Modifications of Antidiuretic
Response to Vasopressin

• NSAIDs (indomethacin)
• Carbamazepine
• Chlorpropamide

• Lithium (PTH)
• Demeclocycline

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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

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Vasopressin Receptor Agonists and Antagonists

• Arginine vasopressin (AVP)
• Desmopressin (DDAVP)
• Mozavaptan
• Telipressin (Glypressin)

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Vasopressin Receptor Agonists And Antagonists
V1R agonist Terlipressin
V1R antagonist Relcovaptan
V1R /V2R antagonist Conivaptan
V2R antagonist Mozavaptan
V2R antagonist Tolvaptan
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Diseases Affecting the Vasopressin system

• Diabetes Insipidus (DI)
• Central DI
• Nephrogenic DI
• SIADH ( lethargy, anorexia, nausea, vomiting,
  muscle cramp, coma, convulsions, and death)

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Clinical Summary Pharmacology of Vasopressin
Peptides V1 receptor-mediated therapeutic
applications

• 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

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?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

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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

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Future Directions in Vasopressin Analogues

• V1a selective antagonists
• Dysmenorrhea
• Preterm Labor
• Raynouds syndrome

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Future Directions in Vasopressin Analogues

• V1b selective antagonists
• Stress-related disorders
• Anxiety
• Depression
• ACTH-secreting tumors
• Cushings syndrome

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Future Directions in Vasopressin Analogues V2
selective antagonists

• Heart failure
• SIADH
• Cirrhosis
• Hyponatremia

• Brain edema
• Nephrotic syndrome
• Diabetic nephropathy
• Glucoma

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Future Directions in Vasopressin Analogues V2
selective agonists

• Central DI
• Nocturnal enuresis
• Nocturnal polyuria
• Urinary incontinence

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