desmopressin acetate

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
Identifiers
CAS number	16679-58-6
ATC code	H01BA02
PubChem	5311065
DrugBank	BTD00112
ChemSpider	10481973
Chemical data
Formula	C46H64N14O12S2
Mol. mass	1069.22 g/mol
Pharmacokinetic data
Bioavailability	Variable; 0.08–0.16% (oral)
Protein binding	50%
Metabolism	?
Half life	1.5–2.5 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	B2(AU) B(US)
Legal status	POM(UK) ℞-only(US)
Routes	IV, IM, SC, intranasal, oral

Desmopressin (trade names: DDAVP, Stimate, Minirin) is a synthetic replacement for vasopressin, the hormone that reduces urine production during sleep. It may be taken nasally, intravenously, or as a pill. Doctors prescribe Desmopressin most frequently for treatment of diabetes insipidus or bedwetting.

In December 2007, US drug regulators banned using desmopressin nasal sprays for treating bedwetting, but said that desmopressin pills are still a safe bedwetting treatment for otherwise healthy patients. The regulators reviewed the drug after two patients using desmopressin nasal sprays died from hyponatremia, an imbalance of sodium levels in the body. [1]

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 resorption. It also stimulates release of factor VIII 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

Bedwetting

Doctors prescribe desmopressin frequently for treatment of bedwetting. It is usually in the form of Desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to stay dry than those taking a placebo. [2] The drug replaces the antidiuretic hormone for a single night with no cumulative effect.

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 pills could still be considered safe for bedwetting 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.

This is because desmopressin works by limiting the amount of water that is eliminated in the urine. A healthy body needs to maintain a balance of water and salt (sodium). If sodium levels become too low (hyponatremia) - either as a result or 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) or severe hemophilia A.

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

Desmopressin nasal is in the FDA pregnancy category B. Drugs in this category are not expected to harm an unborn baby.

See also

• diabetes insipidus
• hemophilia A
• von Willebrand disease

References

• 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.