Desmopressin

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Desmopressin
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 namesDdavp, Stimate
AHFS/Drugs.commonograph
Pregnancy cat.B2 (AU) B (US)
Legal statusPOM (UK) -only (US)
RoutesIV, IM, SC, intranasal, oral
Pharmacokinetic data
BioavailabilityVariable; 0.08–0.16% (oral)
Protein binding50%
Half-life1.5–2.5 hours
ExcretionRenal
Identifiers
CAS number16679-58-6 YesY
ATC codeH01BA02
PubChemCID 5311065
DrugBankDB00035
ChemSpider10481973 YesY
UNIIENR1LLB0FP YesY
KEGGD00291 YesY
ChEMBLCHEMBL376685 YesY
Chemical data
FormulaC46H64N14O12S2 
Mol. mass1069.22 g/mol
 YesY (what is this?)  (verify)
 
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Desmopressin
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 namesDdavp, Stimate
AHFS/Drugs.commonograph
Pregnancy cat.B2 (AU) B (US)
Legal statusPOM (UK) -only (US)
RoutesIV, IM, SC, intranasal, oral
Pharmacokinetic data
BioavailabilityVariable; 0.08–0.16% (oral)
Protein binding50%
Half-life1.5–2.5 hours
ExcretionRenal
Identifiers
CAS number16679-58-6 YesY
ATC codeH01BA02
PubChemCID 5311065
DrugBankDB00035
ChemSpider10481973 YesY
UNIIENR1LLB0FP YesY
KEGGD00291 YesY
ChEMBLCHEMBL376685 YesY
Chemical data
FormulaC46H64N14O12S2 
Mol. mass1069.22 g/mol
 YesY (what is this?)  (verify)

Desmopressin (trade names: DDAVP, DesmoMelt, Stimate, Minirin) 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 modified form of the normal human hormone arginine vasopressin, 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.

Clinical uses[edit]

Nocturnal Enuresis[edit]

Doctors prescribe desmopressin frequently for treatment. It is usually in the form of desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to sleep without disruption than with placebo. [1] [2] Examples of these situations are overnight camp and sleepovers.

US drug regulators banned treating bedwetting with desmopressin nasal sprays after two patients died and 59 other patients suffered seizures. The patients were using desmopressin when they developed hyponatremia, an imbalance of the body's sodium levels. [3]

FDA regulators said that desmopressin tablets could still be considered safe for nocturnal enuresis treatment, as long as the patient was otherwise healthy. Patients must stop taking desmopressin if they become sick and have severe vomiting and diarrhea, fever, the flu, or severe cold. They should also be very cautious during hot weather or following strenuous exercise that may make them thirsty.

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. 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]