Desmopressin (DDAVP)

aka. 1-desamino-8-D-arginine vasopressin or 1-deamino-8-D-arginine vasopressin (DDAVP)

CLASS

  • synthetic vasopressin analogue

INDICATIONS

  1. Central diabetes insipidus (DI)
  2. Mild-moderate Type A haemophilia
  3. von Willebrand disease (Type 1)

ADMINISTRATION / DOSING (Adult)

  • intravenous (IV) / subcutaneous (SC) / intramuscular (IM) / oral (PO) / intranasal (IN) / sublingual (SL)
  • Diabetes Insipidus
    • SC/IM/IV: 1-4 microgs daily in 1-2 doses (dose at Institution 1 is 0.5 microgs IV)
    • IN: 10-40 microgs, or 40 mircogs divided into 2-3 doses
    • SL: 60-120 microgs TDS (range 120-720 microgs daily)
    • PO: Initially 0.05mg BD (maintenance usually 0.1-0.8 mg/day in divided doses)
    • Of note: ADH activity of 4 microgs IV desmopressin is equivalent to 16 IU of vasopressin
  • Haemophilia A (mild) and von Willeband disease Type 1 (mild-moderate)
    • IV infusion: 0.3 microgs/kg diluted in 50mL 0.9% saline administered over 15-30 min
      • Administer 30 min prior to procedure
    • IN: <50kg 150microgs one nostril / >50kg 150 microgs each nostril
      • Initial response seen after 30 min

MECHANISM OF ACTION

  • Predominantly acts via V2 receptors (Gs-protein-coupled receptors adenylyl cyclase / cAMP):
    • Basolateral membrane of the collecting duct in the kidneys –> insertion of aquaporin (AQP-2) water channels into the apical membrane –> increases water reabsorption
    • Vascular endothelium –> releases von Willebrand factor and factor VIII –> Reduces bleeding time
    • Vascular smooth muscle –> vasodilation (minor, at standard doses)
  • Compared with vasopressin which has an ADH:vasopressor action ratio of 1, desmopressin has a ratio of 2000-4000:1
  • Lesser actions:
    • V1 receptors: Vascular smooth muscle of systemic, splanchnic, renal and coronary circulations –> potent vasoconstriction. Also on platelets –> enhances intracellular Ca2+ facilitating thrombosis
    • V3 receptors: Pituitary –> ACTH release –> increased cortisol secretion
    • OTR (Oxytocin receptor subtypes): Mammary glands, myometrium, endometrium –> uterine contraction and milk ejection

PHARMACEUTICS

  • Stored at 2-8oC IN / IV, room temperature for PO and SL
  • White, fluffy powder, soluble in water and glacial acetic acid
  • Excipients: sodium chloride, hydrochloric acid and water for injections
  • IV form comes in 4 microgs/mL or 15 microgs/mL
  • pH: IN form 5.5 / IV form 4

PHARMACOKINETICS

  • Absorption
    • Bioavailability: SC 85% / IN 3.3-4.1% / PO 0.16%
    • TMAX: IN 15-45 min / PO 50-55 min
  • Distribution
    • Vd 26.5 litres
    • Distribution half-life: ~8 min
  • Metabolism
    • Minimally hepatically metabolised
  • Elimination
    • Renal excretion 52% unchanged
    • Similar to ADH, yet slower
    • 7.6 L/h clearance
    • T1/2: IN 3-4 hours / IV 1.5-3 hours

PHARMACODYNAMICS

  • CNS:
    • Increase ACTH release from pituitary –> Cortisol release
    • Headache, seizures
  • CVS
    • Low doses causes vasodilation, high doses may cause vasoconstriction
    • Facial flushing
  • RESP
    • Rhinitis, nosebleed
  • GIT
    • Nausea, abdominal cramps
  • GUT
    • Slight oxytocic effect –> uterine contraction
    • Water retention via ADH action in renal tubules–> can lead to intoxication with polydipsia and use in heart failure
  • HAEM
    • Induces release of vWF and factor VIII from endothelial cells –> reduced bleeding time
    • Thought to also: increase density of glycoprotein receptors on the platelet, enhances ability to form procoagulant platelets and increases platelet-dependant thrombin generation by enhancing Na+ and Ca2+
    • May induce platelet aggregation in von Willebrand disease Type IIb
  • OTHER
    • Hyponatraemia

CONTRAINDICATIONS

  • Type IIb von Willebrand’s disease
    • Platelet activation may be induced
  • SIADH
  • Hyponatraemia
  • Heart failure
  • Polydipsia
  • Renal failure when CrCl <50mL/min

VASOPRESSIN AND ITS ANALOGUES

  • Argipressin (synthetic vasopressin)
    • Use: Septic shock / cardiac arrest / DI
    • ADH-to-pressor ratio of 1
    • Duration of action: ~20 min
  • Desmopressin
    • Use: DI / von Willebrand disease / Type A haemophilia
    • Reduceed vasopressor activity, enhanced ADH-pressor potency, and prolonged duration of action
    • ADH-to-pressor ratio of 2000-4000:1, duration of action 2-6 hours (Secondary to resistance against enzymatic cleavage and delayed absorption from the nasal mucosa
  • Terlipressin
    • Use: Hepatorenal syndrome / variceal haemorrhage / Septic shock
    • Quite selective for splanchnic circulation vasoconstriction
    • Duration of action 2-10 hours

LITFL

References

  • Australian Injectable Drugs Handbook, 8th Edition. (2022). Retrieved 27 August 2022, from https://aidh.hcn.com.au/
  • Australian Medicines Handbook. (2022). Retrieved 27 August 2022, from https://amhonline.amh.net.au/       
  • Colucci G, Stutz M, Rochat S, Conte T, Pavicic M, Reusser M, Giabbani E, Huynh A, Thürlemann C, Keller P, Alberio L. The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects. Blood. 2014 Mar 20;123(12):1905-16. doi: 10.1182/blood-2013-04-497123. Epub 2014 Jan 17. PMID: 24443440. [Full free text]
  • Holmes CL, Landry DW, Granton JT. Science review: Vasopressin and the cardiovascular system part 1–receptor physiology. Crit Care. 2003 Dec;7(6):427-34. doi: 10.1186/cc2337. Epub 2003 Jun 26. PMID: 14624682; PMCID: PMC374366. [Full free text]
  • IBM Micromedex. (2022). Retrieved 27 August 2022, from https://www.micromedexsolutions.com
  • Rang, H., Dale, M., Ritter, J., & Flower, R. (2007). Rang and Dale’s pharmacology (6th ed., pp. 425-426). Edinburgh: Churchill Livingstone Elsevier.

Cite this article as: James Pearlman, "Desmopressin (DDAVP)," In: LITFL - Life in the FastLane, Accessed on September 24, 2022, https://litfl.com/desmopressin/.

Critical Care

Compendium

ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.

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