Desmopressin (DDAVP)
aka. 1-desamino-8-D-arginine vasopressin or 1-deamino-8-D-arginine vasopressin (DDAVP)
CLASS
- synthetic vasopressin analogue
INDICATIONS
- Central diabetes insipidus (DI)
- Mild-moderate Type A haemophilia
- 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) / von Willebrand disease Type 1 (mild-moderate) / Uraemia-related bleeding disorder / Acquired or inherited platelet disorder
- 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
- IV infusion: 0.3 microgs/kg diluted in 50mL 0.9% saline administered over 15-30 min
- Reversal of antiplatelet agent in intracerebral haemorrhage (ICH)
- IV infusion: 0.4 microgs/kg diluted in 50mL 0.9% saline administered over 15-30 min (bolus administration may precipitate hypotension)
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
References and links
LITFL
- CCC – Central diabetes insipidus
- CCC – Vasopressin
- CCC – Terlipressin
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 June 4, 2023, 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.