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Renal 03 Vasopressin

Maloney Pharmacology of Vasopressin

Vasopressin is the main hormone involved in what? The regulation of body fluid osmolality
What can stimulate vasopressin (ADH) release? High plasma osmolality, major hypovolemia, and major hypotension
Where are the vasopressin receptors located? V1 on vascular smooth muscle : V2 on principal cells of renal collecting duct and vascular epithelium
What are the results of binding to V1? Causes vasoconstriction in vascular smooth muscle
What happens when vasopressin binds to V2? V2 receptors on vascular endothelium will release clotting favtor VIII and vWF from storage sites
Without vasopressin, what kind of urine is produced? Dilute urine
The V2 receptor on the basolateral membrane in the collecting duct coupes to Gs. What signaling pathway is activated/inhibited? This activates adenylyl cyclase.
With vasopressin, what type of urine is produced? Concentrated urine
What cells in the collecting ducts do vasopressin bind to? It binds to the basolateral membrane of principal cells
What does activating Gs do? Activates adenylyl cyclase and increases cAMP
Increased cAMP will activate what? Protein kinase A, which will induce water channels to move to the apical membrane, increasing water permeability
Name the two vasopressin agents. Vasopressin and desmopressin
What is the half-life, receptor(s), and route(s) of administration for vasopressin? Short acting (half-life about 10 minutes) : Binds both V1 and V2 : IM, SC, IV
What is the half-life, receptor(s), and route(s) of administration for desmopressin? Long acting (half-life about 75 minutes) : Binds V2>>>V1 : IV, SC, intranasal, oral
Which agent will selectively affect urine output? Desmopressin
Name the clinical uses for vasopressin. Advance Cardiac Life Support : Vasodilatory shock
What is a clinical use for desmopressin? Primary nocturnal enuresis (bed wetting) - use for 4-8 weeks in children >6 with severe NE
How does this happen? Binds to V2 in the kidney -> increases water permeability in the collecting duct -> increase water reabsorption -> decrease urine output
Other clinical uses of desmopressin. Hemophillia A or type I von Willebrand's disease - increase circulating levels of factor VIII and vWF and shorten bleeding time : Central diabetes insipidus
Where is the issue in Central diabetes insipidus? The posterior pituitary does not release vasopressin
Why does desmopressin not work in nephrogenic D.I.? The V2 receptors have insufficient response to binding.
A two year old boy is diagnosed with nephrogenic diabetes insipidus. What drug will be most useful in treating him? Hydroclorothiazide
Why do you give desmopressin for central DI and not vasopressin? Desmopressin is selective for V2 causing less side effects
What are the adverse effects seen with vasopressin (V1) Facial pallor, transient headache, nausea, abdominal cramps, hypertension, coronary vasospasm
Adverse effects associated with vasopressin and desmopressin (V2) Water intoxication, hyponatremia (hypervolemia hyponatremia)
Why do you not use intranasal desmopressin to treat bed wetting? It can cause DEATH
Adverse effects with intranasal desmopressin. Congestion and rhinitis
Created by: bcriss