VWF disease

[chromuffin]

What is the MoA for desmopressin as a therapy for von Willebrand Disease? Pathoma says it increases vWF release from Weibel-Palade bodies but how? Is it the vasoconstrictive properties? I have read that it binds V2 receptors on endothelial cells, so I'm assuming this must be the case? But I also thought desmopressin has relatively little effect on BP.

I'm very much a person that needs fine details to remember. Memorizing just doesn't work out for me.

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[Anti-PD1]

Vasopressin is a secretagogue of VWF. This hormone functions through two receptors, termed V1 and V2, which activate different intracellular second messengers.7 Agonist activity at V2 receptors leads to a rise in intracellular concentrations of cyclic adenosine monophosphate, which in turn induces exocytosis of VWF from its storage sites (ie, Weibel–Palade bodies of endothelial cells) into the circulation. Interestingly, tissue plasminogen activator, a molecule involved in fibrinolysis and therefore in opposition to the effects of VWF, is also released into circulation along with VWF. Desmopressin (1‐desamino‐8‐d‐arginine vasopressin, also abbreviated DDAVP) is a synthetic analogue of vasopressin, which activates only V2 receptors and thus lacks its vasoconstrictor and uterotonic properties. Intravenous or intranasal administration of desmopressin to healthy individuals is followed by a rise in levels of both VWF and its precious cargo, FVIII.2 Individuals who lack V2 receptors—that is, patients with nephrogenic diabetes insipidus—expectedly do not show this increase in VWF and FVIII levels.1,3,7,8

Although originally designed for the treatment of diabetes insipidus, desmopressin emerged as a haemostatic agent, with the appreciation of its effects on coagulation and the lack of the severe side effects associated with vasopressin. The next section discusses the bleeding disorders amenable to treatment with this drug.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2599976/#__sec1title

 

[chromuffin]

Vasopressin is a secretagogue of VWF. This hormone functions through two receptors, termed V1 and V2, which activate different intracellular second messengers.7 Agonist activity at V2 receptors leads to a rise in intracellular concentrations of cyclic adenosine monophosphate, which in turn induces exocytosis of VWF from its storage sites (ie, Weibel–Palade bodies of endothelial cells) into the circulation. Interestingly, tissue plasminogen activator, a molecule involved in fibrinolysis and therefore in opposition to the effects of VWF, is also released into circulation along with VWF. Desmopressin (1‐desamino‐8‐d‐arginine vasopressin, also abbreviated DDAVP) is a synthetic analogue of vasopressin, which activates only V2 receptors and thus lacks its vasoconstrictor and uterotonic properties. Intravenous or intranasal administration of desmopressin to healthy individuals is followed by a rise in levels of both VWF and its precious cargo, FVIII.2 Individuals who lack V2 receptors—that is, patients with nephrogenic diabetes insipidus—expectedly do not show this increase in VWF and FVIII levels.1,3,7,8

Although originally designed for the treatment of diabetes insipidus, desmopressin emerged as a haemostatic agent, with the appreciation of its effects on coagulation and the lack of the severe side effects associated with vasopressin. The next section discusses the bleeding disorders amenable to treatment with this drug.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2599976/#__sec1title

Thanks! Couldn't find it for the life of me.