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Pathway Description
Desmopressin Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2021-11-03
Last Updated: 2023-10-25
Desmopressin is a synthetic analog of vasopressin (anti-diuretic hormone) used to reduce renal excretion of water in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. Anti-diuretic hormone (ADH) is an endogenous pituitary hormone that has a crucial role in the control of the water content in the body. Upon release from the stimulation of increased plasma osmolarity or decreased circulating blood volume, ADH mainly acts on the cells of the distal part of the nephron and the collecting tubules in the kidney. The hormone interacts with V1, V2 or V3 receptors with differing signal cascade systems. Desmopressin displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH.
Desmopressin binds to to V2 receptors in the basolateral membrane of the cells of the distal tubule and collecting ducts of the nephron. V2 receptors are coupled to the Gs protein, and activation of this receptor leads to stimulation of adenylyl cyclase. Stimulation of adenylyl cyclase produces cAMP, which activates protein kinase A (PKA). The resulting intracellular cascades lead to increased rate of insertion of water channels, specifically, aquaporin-2, into the luminal membrane and enhanced the permeability of the membrane to water, to increase water reabsorption from the filtrate. This activity leads to a decrease in urine volume and an increase in urine osmolality.
Desmopressin can be administered intravenously, as a subcutaneous injection, as an intranasal spray, and as a dissolvable sublingual strip. The tablet form has been discontinued in many countries due to the intranasal and sublingual forms having better bioavailability.
Common side effects from taking desmopressin include headaches, tachycardia, and facial flushing. The major adverse effect of desmopressin is hyponatremia (low sodium level in the blood). As desmopressin increases the urine concentration, it can also lead to systemic hyponatremia.
References
Desmopressin Pathway References
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