oxytocin is synthesized in the pvn (son) is synthesized in the pvn (son) (luteal cells, endometrium,...
TRANSCRIPT
OXYTOCINOXYTOCIN
Is synthesized in the PVN (SON)Is synthesized in the PVN (SON)(luteal cells, endometrium, and the (luteal cells, endometrium, and the
placental)placental)
Oxytocin-neurophysin complexOxytocin-neurophysin complex
Neurohypophysis, hypothalamus, Neurohypophysis, hypothalamus, brain stem, and spinal cordbrain stem, and spinal cord
OXYTOCINOXYTOCIN
Stimuli for secretion: dilation of Stimuli for secretion: dilation of the cervix, vagina and from the cervix, vagina and from suckling at the breastsuckling at the breast
Estradiol and RelaxinEstradiol and Relaxin
Ethanol, pain, dehydration, Ethanol, pain, dehydration, hemorrhage and hypovolemiahemorrhage and hypovolemia
Physiological Roles of Physiological Roles of OxytocinOxytocin
Uterus (estrogen and Uterus (estrogen and progestrone)progestrone)
Breast (milk ejection)Breast (milk ejection)
Oxytocin receptors (PG Oxytocin receptors (PG production)production)
Clinical Use of OxytocinClinical Use of Oxytocin Induction of laborInduction of labor
Augmentation of laborAugmentation of labor
Third stage of labor and puerperiumThird stage of labor and puerperium
Oxytocin challenge testOxytocin challenge test
Oxytocin-receptor antagonists Oxytocin-receptor antagonists (Atosiban)(Atosiban)
Vasopressin and Vasopressin and Other Agents Other Agents Affecting the Affecting the
Renal Renal Conservation of Conservation of
WaterWater
INTRODUCTION TO INTRODUCTION TO VASOPRESSINVASOPRESSIN
ADH ADH VasopressorVasopressor NeurotransmitterNeurotransmitter Secretion of ACTHSecretion of ACTH Regulation of CVSRegulation of CVS TemperatureTemperature Visceral functionsVisceral functions Promotes the release of Promotes the release of
coagulation factorscoagulation factors Platelet aggregabilityPlatelet aggregability
Physiology of Physiology of VasopressinVasopressin
Anatomy Anatomy (hypothalamiconeurohypophyseal (hypothalamiconeurohypophyseal system, and renal collecting-duct system, and renal collecting-duct system)system)
Synthesis (SON, PVN)Synthesis (SON, PVN) Parvicellular neuronsParvicellular neurons SynthesisSynthesis Transport and storageTransport and storage ReleaseRelease
Vasopressin Synthesis Vasopressin Synthesis Outside the CNSOutside the CNS
Heart (elevated wall stress)Heart (elevated wall stress)
Adrenal Gland Adrenal Gland (catecholamine secretion)(catecholamine secretion)
Regulation ofRegulation of Vasopressin Vasopressin SecretionSecretion
Hyperosmolality (osmoreceptive complex)Hyperosmolality (osmoreceptive complex) SFO, OVLT, MnPO (Aquaporin 4)SFO, OVLT, MnPO (Aquaporin 4) Hepatic Portal OsmoreceptorsHepatic Portal Osmoreceptors
Hypovolemia and hypotension Hypovolemia and hypotension (baroreceptors in the left atrium, left (baroreceptors in the left atrium, left ventricle, pulmonary veins, carotid sinus ventricle, pulmonary veins, carotid sinus and aorta)and aorta)
Pain, nausea, and hypoxiaPain, nausea, and hypoxia
Modulation of Vasopressin Modulation of Vasopressin SecretionSecretion
StimulatorsStimulators ACh (nAChR)ACh (nAChR) Histamine (H1 Histamine (H1
receptors)receptors) Dopamine (D1 and Dopamine (D1 and
D2 receptors)D2 receptors) GlutamineGlutamine AspartateAspartate CCK, NPY, SP, CCK, NPY, SP,
VIP, PGs, Ag VIP, PGs, Ag ΙΙΙΙ, Ag , Ag IIIIII
InhibitorsInhibitors ANPANP GABAGABA OpioidsOpioids
Pharmacological Agents of Pharmacological Agents of Vasopressin SecretionVasopressin Secretion
VincristineVincristine CyclophosphamiCyclophosphami
dede TCAsTCAs NicotineNicotine EpinephrineEpinephrine MorphineMorphine (HD) (HD) LithiumLithium
EthanolEthanol PhenytoinPhenytoin Morphine (LD) Morphine (LD) FluphenazineFluphenazine HaloperidolHaloperidol PromethazinePromethazine CarbamazepineCarbamazepine
Basic Pharmacology of Basic Pharmacology of VasopressinVasopressin
Vasopressin receptors (V1a, V1b, Vasopressin receptors (V1a, V1b, and V2)and V2)
V1 receptors: Gq-PLC pathwayV1 receptors: Gq-PLC pathway
V2 receptors:V2 receptors: Gs-AC pathwayGs-AC pathway
Mechanisms by which vasopressin Mechanisms by which vasopressin increases the renal conservation of increases the renal conservation of
waterwater
Pharmacological Pharmacological Modifications of Modifications of
Antidiuretic Response to Antidiuretic Response to VasopressinVasopressin
NSAIDs NSAIDs (indomethacin)(indomethacin)
CarbamazepineCarbamazepine
ChlorpropamideChlorpropamide
Lithium (PTH)Lithium (PTH)
DemeclocyclineDemeclocycline
Nonrenal Actions of Nonrenal Actions of VasopressinVasopressin
Cardiovascular SystemCardiovascular System Central Nervous SystemCentral Nervous System(learned behaviors, depression, antipyretic (learned behaviors, depression, antipyretic
factors, modulation CNS autonomic factors, modulation CNS autonomic systems, and secretion of ACTH)systems, and secretion of ACTH)
Blood coagulation (V2 receptors)Blood coagulation (V2 receptors) Contraction of uterus, GIT, platelet Contraction of uterus, GIT, platelet
aggregation and glycogenolysisaggregation and glycogenolysis
Vasopressin Receptor Vasopressin Receptor Agonists and AntagonistsAgonists and Antagonists
Arginine vasopressin (AVP)Arginine vasopressin (AVP)
Desmopressin (DDAVP)Desmopressin (DDAVP)
MozavaptanMozavaptan
Telipressin (Glypressin)Telipressin (Glypressin)
Vasopressin Receptor Agonists And Antagonists
TerlipressinV1R agonist
RelcovaptanV1R antagonist
ConivaptanV1R /V2R antagonist
MozavaptanV2R antagonist
TolvaptanV2R antagonist
Diseases Affecting the Diseases Affecting the Vasopressin systemVasopressin system
Diabetes Insipidus (DI)Diabetes Insipidus (DI)Central DICentral DI
Nephrogenic DINephrogenic DI
SIADH ( lethargy, anorexia, SIADH ( lethargy, anorexia, nausea, vomiting, muscle cramp, nausea, vomiting, muscle cramp, coma, convulsions, and death)coma, convulsions, and death)
Clinical Summary: Clinical Summary: Pharmacology of Pharmacology of
Vasopressin PeptidesVasopressin Peptides V1 receptor-mediated V1 receptor-mediated
therapeutic applicationstherapeutic applications Post operative ileusPost operative ileus Dispel intestinal Dispel intestinal
gasgas Esophageal varicesEsophageal varices Portal hypertensionPortal hypertension Reduce bleeding Reduce bleeding
during acute during acute hemorrhagic hemorrhagic gastritisgastritis
Burn wound Burn wound excisionexcision
cyclophosphade-cyclophosphade-induced induced hemorrhagic hemorrhagic cystitiscystitis
Liver Liver transplantationtransplantation
Cesarean sectionCesarean section Uterine myoma Uterine myoma
resectionresection Vasodilatory shockVasodilatory shock AsystoleAsystole
Clinical Summary: Clinical Summary: Pharmacology of Pharmacology of
Vasopressin PeptidesVasopressin Peptides V2 receptor-mediated V2 receptor-mediated
therapeutic applicationstherapeutic applications Water conservationWater conservation Release of blood coagulation Release of blood coagulation
factors (type I vWB, type IIn vWB, factors (type I vWB, type IIn vWB, factor VIII, uremia and cirrhosis)factor VIII, uremia and cirrhosis)
Primary nocturnal enuresisPrimary nocturnal enuresis Relieve post-lumbar puncture Relieve post-lumbar puncture
headacheheadache
Toxicity, Adverse Effects, Toxicity, Adverse Effects, Contraindications, and Contraindications, and
Drug InteractionsDrug Interactions Marked facial pallorMarked facial pallor Increased intestinal activityIncreased intestinal activity Coronary circulation (CAD)Coronary circulation (CAD) Water intoxicationWater intoxication Acute renal failureAcute renal failure Angina, hypertension, and heart Angina, hypertension, and heart
failurefailure Primary or psychogenic polydipsiaPrimary or psychogenic polydipsia Allergic reactionsAllergic reactions Local adverse effectsLocal adverse effects
Future Directions in Future Directions in Vasopressin AnaloguesVasopressin Analogues
V1a selective antagonistsV1a selective antagonists DysmenorrheaDysmenorrhea
Preterm LaborPreterm Labor
RaynoudRaynoud’’s syndromes syndrome
Future Directions in Future Directions in Vasopressin AnaloguesVasopressin Analogues
V1b selective antagonists V1b selective antagonists Stress-related disordersStress-related disorders
AnxietyAnxiety
DepressionDepression
ACTH-secreting tumorsACTH-secreting tumors
CushingCushing’’s syndrome s syndrome
Future Directions in Future Directions in Vasopressin AnaloguesVasopressin Analogues
V2 selective antagonistsV2 selective antagonists
Heart failureHeart failure
SIADHSIADH
CirrhosisCirrhosis
HyponatremiaHyponatremia
Brain edemaBrain edema
Nephrotic Nephrotic syndromesyndrome
Diabetic Diabetic nephropathynephropathy
GlucomaGlucoma
Future Directions in Future Directions in Vasopressin AnaloguesVasopressin Analogues V2 selective agonistsV2 selective agonists
Central DICentral DI
Nocturnal enuresisNocturnal enuresis
Nocturnal polyuriaNocturnal polyuria
Urinary incontinenceUrinary incontinence