Desmopressin

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 names	Ddavp, 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 Y
ATC code	H01BA02
PubChem	CID 5311065
DrugBank	BTD00112
ChemSpider	10481973 Y
UNII	ENR1LLB0FP Y
KEGG	D00291 Y
ChEMBL	CHEMBL376685 Y
Chemical data
Formula	C46H64N14O12S2
Mol. mass	1069.22 g/mol
SMILES	eMolecules & PubChem
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-/m0/s1 Y Key:NFLWUMRGJYTJIN-NXBWRCJVSA-N Y
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Desmopressin (trade names: DDAVP, Stimate, Minirin) is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet. Doctors prescribe Desmopressin most frequently for treatment of diabetes insipidus or sleep apnea.

Chemistry

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

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 due to stimulation of the V1a 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.

Clinical uses

Sleep Apnea

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] That said, the first-line treatment is usually mouthpiece. Drug therapy tends to have its place only when the mouthpiece system is impractical or not effective. ^[2] Examples of these situations are overnight camp and sleepovers.

US drug regulators banned treating sleep apnea 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 Sleep Apnea 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

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

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 hypothalamus). It is also used in the diagnostic workup for diabetes insipidus, in order to distinguish central from nephrogenic DI.

Side effects

• headaches
• facial flushing
• nausea
• hyponatremia
• seizures

References

1. ^ Evans, JH (2001). "Evidence based management of nocturnal enuresis". BMJ (Clinical research ed.) 323 (7322): 1167–9. PMC 1121645. PMID 11711411. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1121645. 
2. ^ "La prise en charge de l’énurésie nocturne primaire". Paediatr Child Health 10 (10): 616–620. 2005. PMC 2722621. PMID 19668677. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2722621. 
3. ^ 2 Deaths Spur sleep apnea Drug Warning. Webmd.com (2007-12-04). Retrieved on 2011-04-18.
4. ^ [1]^{[dead link]}

Further reading

• 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.