Desmopressin

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Desmopressin
Desmopressin.svg
Desmopressin ball-and-stick.png
Systematic (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
Clinical data
Trade names Ddavp, Minirin, Minirin Melt, Octim, Stimate
AHFS/Drugs.com monograph
Pregnancy cat. B2 (AU) B (US)
Legal status POM (UK) -only (US)
Routes IV, IM, SC, intranasal, oral
Pharmacokinetic data
Bioavailability Variable; 0.08–0.16% (oral)
Protein binding 50%
Half-life 1.5–2.5 hours
Excretion Renal
Identifiers
CAS number 16679-58-6 YesY
ATC code H01BA02
PubChem CID 5311065
DrugBank DB00035
ChemSpider 10481973 YesY
UNII ENR1LLB0FP YesY
KEGG D00291 YesY
ChEMBL CHEMBL376685 YesY
Chemical data
Formula C46H64N14O12S2 
Mol. mass 1069.22 g/mol
 YesY (what is this?)  (verify)

Desmopressin (trade names: DDAVP, DesmoMelt, Minirin, Minirin Melt, Octim, Stimate) is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as an oral or sublingual tablet. Physicians prescribe desmopressin most frequently for treatment of diabetes insipidus, bedwetting, or nocturia.

Chemistry[edit]

Desmopressin (1-desamino-8-D-arginine vasopressin) is a man-made 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).

Mode of action[edit]

Desmopressin works by limiting the amount of water that is eliminated in the urine.

Desmopressin binds to V2 receptors in renal collecting ducts, increasing water reabsorption. It also stimulates release of von Willebrand factor from endothelial cells by acting on the V2 receptor.

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. 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. Desmopressin does not stimulate ACTH release, and therefore does not directly raise blood pressure.[citation needed]

Clinical uses[edit]

Nocturnal Enuresis[edit]

Doctors prescribe desmopressin frequently for treatment of nocturnal enuresis (bedwetting). It is usually prescribed in the form of oral desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to sleep without disruption compared with placebo. [1] [2]

US drug regulators banned treating nocturnal enuresis with desmopressin nasal sprays after two patients died and fifty-nine other patients suffered seizures. The patients were using desmopressin when they developed hyponatremia, an imbalance of the body's sodium levels. [3]

FDA regulators have said that desmopressin tablets can still be considered safe for treatment of nocturnal enuresis as long as the patient 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 condtions or following strenuous exercise, as these conditions can place stress on the body's salt and water balance.

A healthy body needs to maintain a balance of water and salt (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. [4]

Coagulation disorders[edit]

Desmopressin can be used to promote the release of von Willebrand factor (with subsequent increase in factor VIII survival secondary to vWF complexing) in patients with coagulation disorders such as von Willebrand disease, mild hemophilia A (factor VIII deficiency), and thrombocytopenia. It can be used with uremic induced platelet dysfunction. It is not effective in the treatment of hemophilia B (factor IX deficiency), severe hemophilia A, or von Willebrand 2B.

Diabetes insipidus[edit]

Desmopressin is used in the treatment of central diabetes insipidus (DI), to replace endogenous ADH that is missing in the central nervous system type of this disorder (decreased production of ADH from the posterior pituitary). It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from nephrogenic DI.

Side effects[edit]

References[edit]

  1. ^ 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. 
  2. ^ "La prise en charge de l’énurésie nocturne primaire". Paediatr Child Health 10 (10): 616–620. 2005. PMC 2722621. PMID 19668677. 
  3. ^ 2 Deaths Spur sleep apnea Drug Warning. Webmd.com (2007-12-04). Retrieved on 2011-04-18.
  4. ^ [1][dead link]

Further reading[edit]

  • Leissinger C, Becton D, Cornell C Jr, Cox Gill J. 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 2001;7:258-66. PMID 11380629.