Desmopressin

Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels.[1] In hemophilia A and von Willebrand disease, it should only be used for mild to moderate cases.[1] It may be given in the nose, by injection into a vein, by mouth, or under the tongue.[1]

Desmopressin
Clinical data
Trade namesDDAVP (deamino D-arginine vasopressin), Minrin, others
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B2
Routes of
administration		IV, IM, SC, intranasal, by mouth, under the tongue
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityVariable; 0.08–0.16% (by mouth)
Protein binding50%
Elimination half-life1.5–2.5 hours
ExcretionKidney
Identifiers
IUPAC name
  • (2S)-N-[(2R)-1-[(2-amino-2-oxoethyl)amino]-5-
    (diaminomethylideneamino)-1-oxopentan-2-yl]-1-
    [(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-10-
    (3-amino-3-oxopropyl)-16-[(4-hydroxyphenyl)methyl]-
    6,9,12,15,18-pentaoxo-13-(phenylmethyl)1,2-dithia-
    5,8,11,14,17-pentazacycloicosane-4-carbonyl]
    pyrrolidine-2-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.037.009
Chemical and physical data
FormulaC46H64N14O12S2
Molar mass1069.22 g·mol−1
3D model (JSmol)
SMILES
  • c1ccc(cc1)C[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSCCC(=O)N[C@H](C(=O)N2)Cc3ccc(cc3)O)C(=O)N4CCC[C@H]4C(=O)N[C@H](CCCNC(=N)N)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N
InChI
  • InChI=1S/C46H64N14O12S2/c47-35(62)15-14-29-40(67)58-32(22-36(48)63)43(70)59-33(45(72)60-18-5-9-34(60)44(71)56-28(8-4-17-52-46(50)51)39(66)53-23-37(49)64)24-74-73-19-16-38(65)54-30(21-26-10-12-27(61)13-11-26)41(68)57-31(42(69)55-29)20-25-6-2-1-3-7-25/h1-3,6-7,10-13,28-34,61H,4-5,8-9,14-24H2,(H2,47,62)(H2,48,63)(H2,49,64)(H,53,66)(H,54,65)(H,55,69)(H,56,71)(H,57,68)(H,58,67)(H,59,70)(H4,50,51,52)/t28-,29+,30+,31+,32+,33+,34+/m1/s1 N
  • Key:NFLWUMRGJYTJIN-PNIOQBSNSA-N N
 NY (what is this?)  (verify)

Common side effects include headaches, diarrhea, and low blood sodium.[1] The low blood sodium that results may cause seizures.[1] It should not be used in people with significant kidney problems or low blood sodium.[1] It appears to be safe to use during pregnancy.[1] It is a synthetic analogue of vasopressin, the hormone that plays roles in the control of the body’s osmotic balance, blood pressure regulation, kidney function,[2] and reduction of urine production.[1]

Desmopressin was approved for medical use in the United States in 1978.[1] It is on the World Health Organization's List of Essential Medicines.[3] It is available as a generic medication.[1]

Medical uses

Bed wetting

Desmopressin is used to treat nocturnal enuresis (bedwetting). It is usually prescribed in the form of desmopressin acetate, by mouth. Children taking DDAVP have 2.2 fewer wet nights per week and are 4.5 times more likely to sleep without disruption compared with placebo.[4][5]

Nighttime urination

In 2017, the FDA approved Desmopressin has some benefit for adults who have problems with night time urination (known as nocturia).[6][7]

Bleeding disorders

Desmopressin (DDAVP) is usually the first line treatment for mild to moderate type 1 von Willebrand disease.[1] It is not recommended in severe disease or in those with abnormal factor VIII.[1] Usefulness in type 2A, 2M, or 2N von Willebrand disease is variable.[1] Generally not recommended in 2B and type 3 von Willebrand disease.[1]

Desmopressin is only recommended in mild hemophilia A.[1] It may be used both for bleeding due to trauma or to try to prevent bleeding due to surgery.[1] It is not effective in the treatment of hemophilia B (factor IX deficiency) or severe hemophilia A.[1] May also be used in uremia induced bleeding.[1]

Diabetes insipidus

Desmopressin is used in the treatment of central diabetes insipidus (DI) as a replacement for endogenous antidiuretic hormone (ADH) that is in insufficient quantity due to decreased or non-existent secretion or production of ADH by the posterior pituitary or hypothalamus, respectively. It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from DI due to the kidneys. Desmopressin is not effective at treating nephrogenic DI, thus a positive response is generally indicative of central DI.

Side effects

US drug regulators added warning to the nasal sprays after two people died and fifty-nine other people had seizures. This occurred due to hyponatremia, a deficit of the body's sodium levels, and the nasal spray is no longer approved for use in children in the United States.[8] However, US drug regulators have said that desmopressin tablets can still be considered safe for treatment of nocturnal enuresis in children as long as the person is otherwise healthy.

Patients must stop taking desmopressin if they develop severe vomiting and diarrhea, fever, the flu, or severe cold. Patients should also be very cautious about taking desmopressin during hot weather conditions or following strenuous exercise, as these conditions can place stress on the body's electrolyte and water balance.

A body needs to maintain a balance of water and (sodium). If sodium levels become too low (hyponatremia) – either as a result of increased water take-up or reduced salt levels – a person may have seizures and, in extreme cases, may die.[9]

Mechanism of action

Desmopressin works by limiting the amount of water that is eliminated in the urine; that is, it is an antidiuretic. It works at the level of the renal collecting duct by binding to V2 receptors, which signal for the translocation of aquaporin channels via cytosolic vesicles to the apical membrane of the collecting duct. The presence of these aquaporin channels in the distal nephron causes increasing water reabsorption from the urine, which becomes passively re-distributed from the nephron to systemic circulation by way of basolateral membrane channels.[10] Desmopressin also stimulates release of von Willebrand factor from endothelial cells by acting on the V2 receptor. It also increases endogenous levels of factor VIII, making it useful in the treatment of hemophilia A.[11]

Desmopressin is degraded more slowly than recombinant vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure, while vasopressin may cause arterial hypertension.[12] Vasopressin stimulates the release of ACTH, which indirectly increases responsiveness of alpha-1 receptor in blood vessel smooth muscle, increasing vessel tone and blood pressure.[2] Several studies have shown that Desmopressin does not stimulate ACTH release (except in Cushing's Disease),[13][14][15] and therefore does not directly raise blood pressure, however, one study showed that it stimulates ACTH release in over 50% of healthy subjects.[16] Additionally, desmopressin is able to enhance ACTH and cortisol release in normal subjects following oCRH administration, but not in patients with anorexia nervosa.[15]

Chemistry

Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic form of the normal human hormone arginine vasopressin (the antidiuretic hormone, or ADH), a peptide containing nine amino acids.

Compared to vasopressin, desmopressin's first amino acid has been deaminated, and the arginine at the eighth position is in the dextro rather than the levo form (see stereochemistry).

References
  1. "Desmopressin Acetate". The American Society of Health-System Pharmacists. Archived from the original on 3 December 2016. Retrieved 2 December 2016.
  2. Cuzzo, Brian; Padala, Sandeep A.; Lappin, Sarah L. (2021), "Physiology, Vasopressin", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30252325, retrieved 2021-06-29
  3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. Evans, JH (2001). "Evidence based management of nocturnal enuresis". BMJ (Clinical Research Ed.). 323 (7322): 1167–9. doi:10.1136/bmj.323.7322.1167. PMC 1121645. PMID 11711411.
  5. "La prise en charge de l'énurésie nocturne primaire". Paediatr Child Health. 10 (10): 616–620. 2005. doi:10.1093/pch/10.10.616. PMC 2722621. PMID 19668677.
  6. Ebell, MH; Radke, T; Gardner, J (Sep 2014). "A systematic review of the efficacy and safety of desmopressin for nocturia in adults". The Journal of Urology. 192 (3): 829–35. doi:10.1016/j.juro.2014.03.095. PMID 24704009.
  7. "FDA approves first treatment for frequent urination at night due to overproduction of urine". www.fda.gov (Press release). 3 March 2017. Archived from the original on 2017-03-06.
  8. Miranda Hitti (4 December 2007). "2 Deaths Spur sleep apnea Drug Warning". WebMD. Archived from the original on 2007-12-07. Retrieved 2011-04-18.
  9. "Information for Healthcare Professionals — Desmopressin Acetate (marketed as DDAVP Nasal Spray, DDAVP Rhinal Tube, DDAVP, DDVP, Minirin, and Stimate Nasal Spray)". Center for Drug Evaluation and Research. FDA. December 4, 2007. Archived from the original on December 13, 2007.
  10. Friedman FM, Weiss JP (December 2013). "Desmopressin in the treatment of nocturia: clinical evidence and experience". Ther Adv Urol. 5 (6): 310–7. doi:10.1177/1756287213502116. PMC 3825109. PMID 24294289.
  11. Loomans, Janneke I.; Kruip, Marieke J.H.A.; Carcao, Manuel; Jackson, Shannon; van Velzen, Alice S.; Peters, Marjolein; Santagostino, Elena; Platokouki, Helen; Beckers, Erik; Voorberg, Jan; van der Bom, Johanna G.; Fijnvandraat, Karin (March 2018). "Desmopressin in moderate hemophilia A patients: a treatment worth considering". Haematologica. 103 (3): 550–557. doi:10.3324/haematol.2017.180059. ISSN 0390-6078. PMC 5830393. PMID 29305412.
  12. Sharman, Andrew; Low, James (2008-08-01). "Vasopressin and its role in critical care". Continuing Education in Anaesthesia, Critical Care & Pain. 8 (4): 134–137. doi:10.1093/bjaceaccp/mkn021. ISSN 1743-1816.
  13. Pecori Giraldi, F; Marini, E; Torchiana, E; Mortini, P; Dubini, A; Cavagnini, F (June 2003). "Corticotrophin-releasing activity of desmopressin in Cushing's disease: lack of correlation between in vivo and in vitro responsiveness". The Journal of Endocrinology. 177 (3): 373–9. doi:10.1677/joe.0.1770373. PMID 12773117.
  14. Colombo, P; Passini, E; Re, T; Faglia, G; Ambrosi, B (June 1997). "Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess". Clinical Endocrinology. 46 (6): 661–8. doi:10.1046/j.1365-2265.1997.1330954.x. PMID 9274696. S2CID 23167207.
  15. Foppiani, L; Sessarego, P; Valenti, S; Falivene, MR; Cuttica, CM; Giusti Disem, M (October 1996). "Lack of effect of desmopressin on ACTH and cortisol responses to ovine corticotropin-releasing hormone in anorexia nervosa". European Journal of Clinical Investigation. 26 (10): 879–83. doi:10.1111/j.1365-2362.1996.tb02133.x. PMID 8911861. S2CID 34560015.
  16. Scott, LV; Medbak, S; Dinan, TG (November 1999). "ACTH and cortisol release following intravenous desmopressin: a dose-response study". Clinical Endocrinology. 51 (5): 653–8. doi:10.1046/j.1365-2265.1999.00850.x. PMID 10594528. S2CID 27334220.

Further reading
  • Leissinger, C; Becton, D; Cornell, C Jr; Cox Gill, J (2001). "High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A.". Haemophilia. 7 (3): 258–66. doi:10.1046/j.1365-2516.2001.00500.x. PMID 11380629. S2CID 20472310.
  • "Desmopressin". Drug Information Portal. U.S. National Library of Medicine.
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