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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. OXYTOCIN. Stimuli for secretion: dilation of the cervix, vagina and from suckling at the breast

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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
oxytocin1
OXYTOCIN
  • Stimuli for secretion: dilation of the cervix, vagina and from suckling at the breast
  • Estradiol and Relaxin
  • Ethanol, pain, dehydration, hemorrhage and hypovolemia
physiological roles of oxytocin
Physiological Roles of Oxytocin
  • Uterus (estrogen and progestrone)
  • Breast (milk ejection)
  • Oxytocin receptors (PG production)
clinical use of oxytocin
Clinical Use of Oxytocin
  • Induction of labor
  • Augmentation of labor
  • Third stage of labor and puerperium
  • Oxytocin challenge test
  • Oxytocin-receptor antagonists (Atosiban)
introduction to vasopressin
INTRODUCTION TO VASOPRESSIN
  • ADH
  • Vasopressor
  • Neurotransmitter
  • Secretion of ACTH
  • Regulation of CVS
  • Temperature
  • Visceral functions
  • Promotes the release of coagulation factors
  • Platelet aggregability
physiology of vasopressin
Physiology of Vasopressin
  • Anatomy (hypothalamiconeurohypophyseal system, and renal collecting-duct system)
  • Synthesis (SON, PVN)
  • Parvicellular neurons
  • Synthesis
  • Transport and storage
  • Release
vasopressin synthesis outside the cns
Vasopressin Synthesis Outside the CNS
  • Heart (elevated wall stress)
  • Adrenal Gland (catecholamine secretion)
regulation of vasopressin secretion
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
modulation of vasopressin secretion
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
pharmacological agents of vasopressin secretion
Vincristine

Cyclophosphamide

TCAs

Nicotine

Epinephrine

Morphine(HD)

Lithium

Ethanol

Phenytoin

Morphine (LD)

Fluphenazine

Haloperidol

Promethazine

Carbamazepine

Pharmacological Agents of Vasopressin Secretion
basic pharmacology of vasopressin
Basic Pharmacology of Vasopressin
  • Vasopressin receptors (V1a, V1b, and V2)
  • V1 receptors: Gq-PLC pathway
  • V2 receptors:Gs-AC pathway
pharmacological modifications of antidiuretic response to vasopressin
NSAIDs (indomethacin)

Carbamazepine

Chlorpropamide

Lithium (PTH)

Demeclocycline

Pharmacological Modifications of Antidiuretic Response to Vasopressin
nonrenal actions of vasopressin
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
vasopressin receptor agonists and antagonists
Vasopressin Receptor Agonists and Antagonists
  • Arginine vasopressin (AVP)
  • Desmopressin (DDAVP)
  • Mozavaptan
  • Telipressin (Glypressin)
diseases affecting the vasopressin system
Diseases Affecting the Vasopressin system
  • Diabetes Insipidus (DI)

Central DI

Nephrogenic DI

  • SIADH ( lethargy, anorexia, nausea, vomiting, muscle cramp, coma, convulsions, and death)
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

Clinical Summary: Pharmacology of Vasopressin PeptidesV1 receptor-mediated therapeutic applications
clinical summary pharmacology of vasopressin peptides
‍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
toxicity adverse effects contraindications and drug interactions
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
future directions in vasopressin analogues
Future Directions in Vasopressin Analogues

V1a selective antagonists

  • Dysmenorrhea
  • Preterm Labor
  • Raynoud’s syndrome
future directions in vasopressin analogues1
Future Directions in Vasopressin Analogues

V1b selective antagonists

  • Stress-related disorders
  • Anxiety
  • Depression
  • ACTH-secreting tumors
  • Cushing’s syndrome
future directions in vasopressin analogues v2 selective antagonists
Heart failure

SIADH

Cirrhosis

Hyponatremia

Brain edema

Nephrotic syndrome

Diabetic nephropathy

Glucoma

Future Directions in Vasopressin AnaloguesV2 selective antagonists
future directions in vasopressin analogues v2 selective agonists
Future Directions in Vasopressin AnaloguesV2 selective agonists
  • Central DI
  • Nocturnal enuresis
  • Nocturnal polyuria
  • Urinary incontinence