You are on page 1of 2

Books ?

Desmopressin
McCarty TS, Shah AD.

Publication Details

Continuing Education Activity


Desmopressin is a drug that acts on the vasopressin
receptors of the body. It has many relevant clinical
uses, ranging from nocturnal enuresis to
hemophilia. While this drug is relatively safe to
use, there are certain side effects to be kept in mind
for patients receiving the drug, as well as specific
contraindications that limit the population that can
receive desmopressin. This activity reviews the
indications, mechanism of action,
contraindications, and adverse effects. It will also
explore the proper monitoring of patients on
desmopressin and the role of the inter-professional
team required to enhance the outcomes for the
patients taking the drug.

Objectives:

Identify the indications to use desmopressin in


a patient.
Describe the mechanism of action of
desmopressin.
Review the potential adverse effects of
desmopressin.
Summarize the role of an integrated inter-
professional team involved in the treatment of
the patients receiving desmopressin.

Access free multiple choice questions on this topic.

Indications
Desmopressin (1-deamino-8-D-arginine
vasopressin) is a synthetic analog of vasopressin,
aka antidiuretic hormone created in 1977 used in
the treatment of a wide variety of medical
conditions to include nocturnal polyuria,
hemophilia A, diabetes insipidus, Willebrand
disease, uremic bleeding, as well as many off label
uses such as an adjunct with hypertonic saline to
prevent rapid sodium correction, intracranial
hemorrhage associated with varying antiplatelet
agents, and trauma resuscitation with active
hemorrhage.[1][2][3]

Nocturnal polyuria is a commonly encountered


condition seen almost exclusively in the pediatric
population, which is responsive to both oral and
intranasal desmopressin. Desmopressin is also
available to adults who awaken more than two
times a night to void.[4]

Hemophilia A is an X-linked autosomal recessive


disorder characterized by the deficiency or absence
of the clotting factor VIII.[5] Factor VIII is an
integral component of the intrinsic coagulation
pathway, which, when combined with von
Willebrand factor, produces the active factor VIIIA,
the cofactor responsible for transforming factor X
to factor Xa. Factor Xa activates IIa (thrombin) to
enable fibrin formation, all of which are integral to
the coagulation cascade.[1] As such, a deficiency in
factor VIII results in recurrent bleeding,
particularly following surgical procedures or
extractions.[5] Patients with hemophilia A are also
at increased risk of major bleeding secondary to
minor injuries, such as hemarthrosis and immediate
and/or delayed bleeding following trauma.
[5] Desmopressin in the intranasal or intravenous
form has FDA approval for the use in mild to
moderate cases of Hemophilia A, substituted with
Factor VIII.

Diabetes insipidus (DI) classically presents with


polyuria and polydipsia and can be secondary to
multiple other conditions.[6] The two primary types
of diabetes inspidus include nephrogenic and
central. Nephrogenic diabetes insipidus indicates
the inability of the kidneys to respond to
antidiuretic hormone or can arise secondary
to long-term lithium use or overdose, as well as any
multitude of disorders that affect the inherent
ability of the kidneys to function optimally.[7]
[8] Central diabetes insipidus occurs secondary to
the inability of the hypothalamus to create ADH
and can occur as a result of central neurologic
system or head trauma, CNS tumors such as
craniopharyngioma, or germinoma, or destruction
of ADH by placental enzymes vasopressinase.[9]
[10][11] In both central and nephrogenic diabetes
insipidus, the urine cannot be concentrated
optimally with water deprivation, and there is a
persistent and continuous excretion of hypotonic
urine. Desmopressin administration can be utilized
to distinguish between central vs. nephrogenic
diabetes insipidus, with a positive response noted in
central diabetes insipidus, meaning the kidneys
respond appropriately to desmopressin with the
expected concentration of the urine and increased
reabsorption of fluids, resulting in eutonic urine.

Uremic platelet dysfunction encompasses multiple


pathways and impairments involving uremia,
ultimately resulting in platelet dysfunction. While
still largely undefined, the most commonly
accepted pathogenesis involves platelet dysfunction
secondary to impaired platelet adhesiveness and
decreased platelet aggregation, as well as abnormal
platelet endothelial interaction. Factors that actively
contribute to platelet dysfunction in uremic patients
include uremic toxins, anemia, and nitric oxide
production.

Uremic platelet dysfunction occurs for several


reasons, including circulating uremic toxins,
platelet aggregation inhibition by increased nitric
oxide production, and anemia resulting in turbulent
rather than a laminar flow of blood products.
[12] Desmopressin given intravenously has been
shown to improve platelet function within 1 hour of
administration.[13]

Von Willebrand disease results from a deficiency in


von Willebrand factor. This factor is essential in
forming the initial platelet plug as a response to
subendothelial tissue exposure.[1] In increasing
order of severity, the different types of the disease
are Type 1, Type 2B and 2M, and type 3.
Indications for desmopressin include the treatment
of types 1, 2B, and 2M. It is also most effective in
treating diseases caused by the variants of
Arg1597Gln, Met740Ile, and Tyr1584Cys.
[14] Desmopressin has also been found, in
observed cases, to decrease the risk of bleeding
complications in pregnant patients suffering from a
mild to moderate form of the disease with a von
Willebrand factor concentration of less than or
equal to 20 IU/dL.[15]

In a limited number of studies of patients with


subarachnoid hemorrhage, some have demonstrated
enough evidence to consider utilizing a single
intravenous dose of desmopressin in patients with
intracranial hemorrhage pending neurosurgical
intervention.[16]

In a select number of patients suffering from severe


hyponatremia with a serum sodium less than 120
mEq/L, studies have demonstrated benefit when
utilizing intravenous 3 percent saline while
simultaneously initiating desmopressin to prevent
rapid correction; decreasing the risk of developing
osmotic demyelination syndrome.[17]

Desmopressin has also been utilized in trauma


resuscitation and post-surgically to receive
hemostasis. Several animal studies have
demonstrated that desmopressin is useful in treating
severe coagulopathy in injured or post-surgical
patients.[16]

Mechanism of Action
Desmopressin is a selective vasopressin V2
receptor agonist present throughout the collecting
ducts and distal convoluted tubules of the kidneys.
[1][18] The V2 receptor is a Gs-protein coupled
receptor, which, when activated, results in a
signaling cascade of adenyl-cyclase, prompting an
increase in cyclic adenosine monophosphate
(cAMP) in the renal tubule cells, ultimately
resulting in increased water permeability. This
activity leads to a decrease in urine volume and an
increase in urine osmolality.

The signaling cascade resulting in the production of


cyclic adenosine monophosphate also induces
exocytosis of von Willebrand factor and factor VIII
from its storage sites, as well as the Weibel-Palade
bodies and the alpha granules of platelets.[1] Von
Willebrand factor functions as the first step in
thrombogenesis, acting as the bridging factor of the
Gp1b factor on platelets to the subendothelial
collagen following tissue injury.[1] By utilizing
synthetic ADH analogs, such as desmopressin, the
clotting cascade is facilitated and can result in
hemostasis.[19]

Administration
Desmopressin can be administered intravenously,
as a subcutaneous injection, as an intranasal spray,
and, most recently, as a dissolvable sublingual
strip. The tablet form has been discontinued in
many countries in favor of the intranasal and
sublingual forms due to the latter's superior
bioavailability.[7] The administration of
intravenous and subcutaneous dose forms of the
drug are predominantly in the hospital setting.
Dosing for both is 0.3 micrograms/kg. Peak blood
concentration after intravenous administration
occurs within 30 to 60 minutes and after
subcutaneous administration within 60 to
90 minutes.[1]

The intranasal form of vasopressin is frequently a


choice when administration occurs at home.
[20] Each spray typically dispenses 150
micrograms.[1] The intranasal dosage is directly
proportional to the patient's weight, with patients
weighing less than 50 kg prescribed one spray, or
150 micrograms, and patients over 50 kg prescribed
2 sprays, or 300 micrograms, every 12 to 24 hours.
This form of the drug reaches peak levels in 60 to
90 minutes.[1]

Sublingual desmopressin, also known as


desmopressin lyophilisate, is administered a
sublingual melt tablet at a dosage of 120
micrograms.[21] It is generally used in the pediatric
population due to the ease of administration and the
increased bioavailability.

Adverse E!ects
The major adverse effect of desmopressin for which
to monitor is hyponatremia. As desmopressin
increases the urine concentration, it can also lead to
systemic hyponatremia with physiology similar to
the syndrome of inappropriate antidiuretic
hormone.[22] In certain instances, the
hyponatremia caused by this drug can precipitate
seizures. The minor adverse effects that may affect
individual patients are headaches, tachycardia, and
facial flushing. There have been certain instances
where patients receiving desmopressin have
suffered from strokes or myocardial infarctions.
However, these cases were rare and did not
establish with certainty that desmopressin exerted a
direct influence in these cases.[1]

Contraindications
Hyponatremia is an absolute contraindication to the
administration of desmopressin, except for
symptomatic hyponatremia warranting aggressive
management with the potential for osmotic
demyelinating syndrome. Desmopressin acts
primarily in the nephron; this drug is
contraindicated in patients with renal impairment.
[22] Also, renal function decreases with age;
therefore, care is necessary when prescribing this
drug in the older population. This drug should also
be avoided in younger patients, especially those
under the age of 2, as it is difficult to restrict water
and fluids in such patients.[1] Additionally, this
drug is ineffective in patients suffering from type 3
von Willebrand disease; therefore, these patients
should not receive the drug.[1] Finally, patients
suffering from thrombocytopenic purpura should
not receive desmopressin, as it can precipitate a
thrombotic event.[1] Lastly, desmopressin is
contraindicated in patients with known
hypersensitivity to desmopressin acetate.

Monitoring
Desmopressin is generally well-tolerated in most
patients. There are a few instances where patients
require monitoring for adverse effects of the drug.
Patients receiving desmopressin need monitoring
for the occurrence of hyponatremia.[23] Symptoms
of hyponatremia include nausea, confusion, or
altered mental status.[24] As patients age, they
should also be continually monitored for declining
renal function, as the therapeutic index and
clearance of the drug will change according to the
renal function.

Toxicity
There is no known antidote to an overdose of
desmopressin. The most worrisome complication to
result from an overdose is water intoxication. This
condition would result in a delayed loss of
consciousness and seizures in some
instances. Patients require immediate admission to
the intensive care unit to be monitored and have
electrolyte correction.[25]

Enhancing Healthcare Team


Outcomes
Desmopressin is a relatively safe drug for use, but it
still requires the efforts of an interprofessional
healthcare team for optimal therapeutic success.
This team will include clinicians, specialists, mid-
level practitioners, nurses, and pharmacists,
coordinating their activities and sharing
information to achieve the best patient outcomes.
[Level 5]

Patients receiving desmopressin to treat hemophilia


A or von Willebrand disease can remain at risk of
bleeding. As such, these patients require an
integrated and cohesive team of specialists
consisting of the primary care physician,
hematologist, and in some instances, a gynecologist
and geneticist. The primary care physician must
ensure that the patients are regularly following up
with a hematologist or a hemophilia treatment
center. In cases of pregnancy, a woman can receive
genetic counseling either before becoming pregnant
or later on during the pregnancy.[5] Parents with
children suffering from these disorders must
understand the complications of the disease and the
proper administration of the medication in the case
of an emergency.

Review Questions
Access free multiple choice questions on this
topic.
Comment on this article.

References
1. Ozgönenel B, Rajpurkar M, Lusher JM. How
do you treat bleeding disorders with
desmopressin? Postgrad Med J. 2007
Mar;83(977):159-63. [PMC free article]
[PubMed]
2. Fein S, Herschkowitz S. Low-Dose
Desmopressin Nasal Spray and FDA Approval.
JAMA. 2017 Sep 19;318(11):1070-1071.
[PubMed]
3. Wiśniewski K, Qi S, Kraus J, Ly B, Srinivasan
K, Tariga H, Croston G, La E, Wiśniewska H,
Ortiz C, Laporte R, Rivière PJ, Neyer G,
Hargrove DM, Schteingart CD. Discovery of
Potent, Selective, and Short-Acting Peptidic V2
Receptor Agonists. J Med Chem. 2019 May
23;62(10):4991-5005. [PubMed]
4. Desmopressin (Nocdurna and Noctiva) for
nocturnal polyuria. Med Lett Drugs Ther. 2019
Mar 25;61(1568):46-48. [PubMed]
5. Konkle BA, Nakaya Fletcher S. Hemophilia A.
In: Adam MP, Mirzaa GM, Pagon RA, Wallace
SE, Bean LJH, Gripp KW, Amemiya A, editors.
GeneReviews® [Internet]. University of
Washington, Seattle; Seattle (WA): Sep 21,
2000. [PubMed]
6. Di Iorgi N, Morana G, Napoli F, Allegri AE,
Rossi A, Maghnie M. Management of diabetes
insipidus and adipsia in the child. Best Pract
Res Clin Endocrinol Metab. 2015
Jun;29(3):415-36. [PubMed]
7. Chanson P, Salenave S. Treatment of
neurogenic diabetes insipidus. Ann Endocrinol
(Paris). 2011 Dec;72(6):496-9. [PubMed]
8. Ott M, Forssén B, Werneke U. Lithium
treatment, nephrogenic diabetes insipidus and
the risk of hypernatraemia: a retrospective
cohort study. Ther Adv Psychopharmacol.
2019;9:2045125319836563. [PMC free article]
[PubMed]
9. Alharfi IM, Stewart TC, Foster J, Morrison GC,
Fraser DD. Central diabetes insipidus in
pediatric severe traumatic brain injury. Pediatr
Crit Care Med. 2013 Feb;14(2):203-9.
[PubMed]
10. Leroy C, Karrouz W, Douillard C, Do Cao C,
Cortet C, Wémeau JL, Vantyghem MC.
Diabetes insipidus. Ann Endocrinol (Paris).
2013 Dec;74(5-6):496-507. [PubMed]
11. Chanson P, Salenave S. Diabetes insipidus and
pregnancy. Ann Endocrinol (Paris). 2016
Jun;77(2):135-8. [PubMed]
12. Boccardo P, Remuzzi G, Galbusera M. Platelet
dysfunction in renal failure. Semin Thromb
Hemost. 2004 Oct;30(5):579-89. [PubMed]
13. Mannucci PM, Remuzzi G, Pusineri F,
Lombardi R, Valsecchi C, Mecca G,
Zimmerman TS. Deamino-8-D-arginine
vasopressin shortens the bleeding time in
uremia. N Engl J Med. 1983 Jan 06;308(1):8-
12. [PubMed]
14. Freitas SDS, Rezende SM, de Oliveira LC,
Prezotti ANL, Renni MS, Corsini CA,
Amorim MVA, Matosinho CGR, Carvalho
MRS, Chaves DG. Genetic variants of VWF
gene in type 2 von Willebrand disease.
Haemophilia. 2019 Mar;25(2):e78-e85.
[PubMed]
15. Goodeve A, James P. von Willebrand Disease.
In: Adam MP, Mirzaa GM, Pagon RA,
Wallace SE, Bean LJH, Gripp KW, Amemiya
A, editors. GeneReviews® [Internet].
University of Washington, Seattle; Seattle
(WA): Jun 4, 2009. [PubMed]
16. Frontera JA, Lewin JJ, Rabinstein AA, Aisiku
IP, Alexandrov AW, Cook AM, Del Zoppo GJ,
Kumar M, Peerschke EI, Stiefel MF,
Teitelbaum JS, Wartenberg KE, Zerfoss CL.
Guideline for Reversal of Antithrombotics in
Intracranial Hemorrhage: Executive Summary.
A Statement for Healthcare Professionals
From the Neurocritical Care Society and the
Society of Critical Care Medicine. Crit Care
Med. 2016 Dec;44(12):2251-2257. [PubMed]
17. Rafat C, Schortgen F, Gaudry S, Bertrand F,
Miguel-Montanes R, Labbé V, Ricard JD,
Hajage D, Dreyfuss D. Use of desmopressin
acetate in severe hyponatremia in the intensive
care unit. Clin J Am Soc Nephrol. 2014
Feb;9(2):229-37. [PMC free article] [PubMed]
18. Narayen G, Mandal SN. Vasopressin receptor
antagonists and their role in clinical medicine.
Indian J Endocrinol Metab. 2012
Mar;16(2):183-91. [PMC free article]
[PubMed]
19. Mannucci PM, Levi M. Prevention and
treatment of major blood loss. N Engl J Med.
2007 May 31;356(22):2301-11. [PubMed]
20. Kaminetsky J, Fein S, Dmochowski R,
MacDiarmid S, Abrams S, Cheng M, Wein A.
Efficacy and Safety of SER120 Nasal Spray in
Patients with Nocturia: Pooled Analysis of 2
Randomized, Double-Blind, Placebo
Controlled, Phase 3 Trials. J Urol. 2018
Sep;200(3):604-611. [PubMed]
21. Gasthuys E, Vermeulen A, Croubels S,
Millecam J, Schauvliege S, van Bergen T, De
Bruyne P, Vande Walle J, Devreese M.
Population Pharmacokinetic Modeling of a
Desmopressin Oral Lyophilisate in Growing
Piglets as a Model for the Pediatric
Population. Front Pharmacol. 2018;9:41.
[PMC free article] [PubMed]
22. Lim CC, Siow B, Choo JCJ, Chawla M, Chin
YM, Kee T, Lee PH, Foo M, Tan CS.
Desmopressin for the prevention of bleeding
in percutaneous kidney biopsy: efficacy and
hyponatremia. Int Urol Nephrol. 2019
Jun;51(6):995-1004. [PubMed]
23. Agersø H, Seiding Larsen L, Riis A, Lövgren
U, Karlsson MO, Senderovitz T.
Pharmacokinetics and renal excretion of
desmopressin after intravenous administration
to healthy subjects and renally impaired
patients. Br J Clin Pharmacol. 2004
Oct;58(4):352-8. [PMC free article] [PubMed]
24. Shrimanker I, Bhattarai S. StatPearls
[Internet]. StatPearls Publishing; Treasure
Island (FL): Jul 25, 2022. Electrolytes.
[PubMed]
25. Segal-Kuperschmit D, Dali-Gotfrid O, Luder
A. [Water intoxication following desmopressin
overdose]. Harefuah. 1997 Apr 01;132(7):465-
7, 527, 526. [PubMed]

Publication Details

Author Information and A"liations

Authors

Troy S. McCarty1; Ankur D. Shah2.

A"liations

1
Naval Medical Center San Diego
2
Warren Alpert Medical School, Brown University

Publication History

Last Update: May 8, 2022.

Copyright
Copyright © 2023, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative


Commons Attribution-NonCommercial-NoDerivatives 4.0
International (CC BY-NC-ND 4.0) (
http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which
permits others to distribute the work, provided that the
article is not altered or used commercially. You are not
required to obtain permission to distribute this article,
provided that you credit the author and journal.

Publisher

StatPearls Publishing, Treasure Island (FL)

NLM Citation

McCarty TS, Shah AD. Desmopressin. [Updated 2022 May


8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2023 Jan-.

You might also like