Desmopressin
**Desmopressin (DDAVP)** is a synthetic analogue of the natural pituitary antidiuretic hormone, arginine vasopressin. It has been structurally modified to significantly enhance its antidiuretic properties while virtually eliminating its vasopressor (blood pressure-raising) activity. In veterinary medicine, it is primarily utilized for two distinct clinical purposes: * **Central Diabetes Insipidus (CDI):** It is the gold standard for both the diagnosis (via response trials) and long-term management of CDI in dogs and cats, effectively resolving severe polyuria and polydipsia. * **Von Willebrand's Disease (vWD):** It is used perioperatively to transiently boost clotting factors in patients with specific subtypes of vWD, though its short duration of action and the rapid development of resistance (tachyphylaxis) limit its long-term utility. **Clinical Pearl:** Because oral bioavailability is exceptionally poor in animals, the human intranasal preparation is most commonly administered *topically into the conjunctival sac* of veterinary patients, providing a reliable and non-invasive route of absorption.
Mecanismo: Desmopressin exerts its effects through two primary mechanisms based on its high affinity for specific receptors: * **Antidiuretic Action (Kidneys):** Desmopressin selectively binds to **V2 receptors** on the basolateral membrane of cells in the renal distal tubules and collecting ducts. This binding activates adenylate cyclase → increases intracellular cAMP → triggers the translocation and insertion of **aquaporin-2 (AQP2)** water channels into the apical membrane. This dramatically increases water permeability, allowing water to be reabsorbed passively back into the bloodstream, thereby concentrating the urine and reducing urine volume. * **Hemostatic Action (Endothelium):** Desmopressin binds to **V2 receptors** on vascular endothelial cells → stimulates the rapid exocytosis of Weibel-Palade bodies → releases stored **von Willebrand factor (vWF)** and **Factor VIII** into the plasma. It also increases plasminogen factor levels.
Dosificación por especie
- Differentiate central diabetes insipidus from nephrogenic form · 1 drop into the conjunctival sac · topical · twice daily · 2-3 days · Dramatic reduction in water intake or >=50% increase in urine concentration gives strong evidence for ADH deficit.
- Central diabetes insipidus · 1-2 drops into the conjunctival sac · topical · once or twice a day · Duration of activity is 8-24 hours.
- Central diabetes insipidus · 1- 4 drops of the intranasal solution in the conjunctival sac · topical · once to twice daily
- Central diabetes insipidus · 2-5 micrograms · SC · once to twice daily · Using intranasal solution parenterally.
- Central diabetes insipidus (oral alternative) · 25-50 micrograms (total dose; 1/4th to 1/2 of a 100 microgram tablet) · PO · q12h · Dose and response may be variable.
- Diagnosis of diabetes insipidus · 20 micrograms · IV · Once
- Diagnosis of diabetes insipidus · 0.05 micrograms/kg · IV · Once · Dilute the nasal spray formulation (0.1 mg/ml) in sterile water. Measure USG every 2 hours. Increase to >=1.025 within 2-7 hours is consistent with central DI.
- Central diabetes insipidus · One drop placed in the conjunctival sac · topical · twice daily (or three times a day) · Using one drop three times a day usually returns urine production to normal.
Vías de administración
Contraindicaciones
- Hypersensitivity to desmopressin
- Type IIB or platelet-type (pseudo) Von Willebrand's disease (may cause platelet aggregation and thrombocytopenia; notably seen in German Shorthair Pointers)
- Hyponatraemia (specifically for modified water deprivation test)
- Renal disease (specifically for modified water deprivation test)
- Dehydration (specifically for modified water deprivation test)
- Hypercalcaemia (specifically for modified water deprivation test)
Efectos adversos
- Eye irritation (following conjunctival administration)
- Hypersensitivity reactions
- Fluid retention (with overdosage)
- Hyponatremia (with overdosage)
- Headache (reported in humans)
Interacciones farmacológicas
- Chlorpropamide · May enhance the antidiuretic effects of desmopressin
- Fludrocortisone · May enhance the antidiuretic effects of desmopressin
- Urea · May enhance the antidiuretic effects of desmopressin
Monitorización
- Serum electrolytes (especially sodium)
- Urine osmolality and/or urine volume
- Bleeding times (when used for Von Willebrand's disease)
- Adrenocortical function (prior to water deprivation test)
- Serum sodium (Clinical Pearl)
- Urine specific gravity (Clinical Pearl)
- Bleeding times/vWF levels if used for bleeding disorders (Clinical Pearl)
Sobredosis
Chronic oral doses of 0.2 mg/kg/day have been given to dogs for 6 months without significant toxicity. However, acute or severe overdosage may lead to **fluid retention** and **hyponatremia** (water intoxication). > **Treatment:** Employ dosage reduction and strict fluid restriction. Monitor serum electrolytes (especially sodium) closely to prevent neurological complications associated with hyponatremia.
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