Desmopressin acetate

Originator

DAV,Ritter,Switz.,1974

The Uses of Desmopressin acetate

Antidiuretic.

Manufacturing Process

β-Benzylmercaptopropionyl-L-tyrosyl-L-phenylalanyl-L-glutaminyl-Lasparaginyl-S-benzyl-L-cysteinyl-L-prolyl-NG-tosyl-D-arginyl-glycinamide (0.5 g) is reduced with sodium in liquid ammonia. The liquid ammonia is then evaporated and the residue dissolved in 5% aqueous acetic acid (800 ml). The solution is filtered to remove the undissolved portion and the filtrate is adjusted to a pH of 6.5 to 7 by addition of aqueous sodium hydroxide and it is then oxidized by known procedure, cf. Kimbrough, R.D., Jr.; Cash, W.D.; Branda, L.A.; Chan, W.Y.; and Du Vigneaud, V.; J. Biol. Chem. 238,1411 (1963). The reaction mixture is thereupon adjusted to a pH of 4 to 4.5 by addition of acetic acid. The peptide is applied to a column of a carboxylate ion exchange resin, is eluted with 50% aqueous acetic acid and isolated by lyophilization (freeze-drying). The crude product is purified by known procedure using a carrier-free high-voltage electrophoresis, cf. Zaoral, M.; Sorm, F.; Collection Czechoslov. Chem Communs, 31, 310 (1966). Yield, 100 to 200 mg of 1-deamino-8-D-argine-vasopressin.

brand name

Concentraid (Ferring Pharmaceuticals); Ddavp (Sanofi Aventis); Stimate (ZLB Behring).

Therapeutic Function

Antidiuretic

General Description

Desmopressin acetate(DDAVP, Stimate) is synthetic 1-desamino-8-D-argininevasopressin. Its efficacy, ease of administration (intranasal),long duration of action, and lack of side effects make itthe drug of choice for the treatment of central diabetesinsipidus. It may also be administered intramuscularly orintravenously. It is preferred to vasopressin injectionand oral antidiuretics for use in children. It is indicatedin the management of temporary polydipsia and polyuriaassociated with trauma to, or surgery in, the pituitary region.

Clinical Use

Desmopressin, as its acetate salt, is a synthetic analogue of vasopressin in which the Nterminal Cys is devoid of its α-amino function (1-Deamino) and where Arg8 is present as its D-isomer (D-Arg8), thus the commercial acronym DDAVP. The presence of D-Arg and the absence of the N-terminal amine in the desmopressin structure have increased its half-life such that it is available for oral, parenteral, or nasal use. It is used by all three of these routes of administration to prevent or control polydipsia (excessive thirst), polyuria, and dehydration of patients with diabetes insipidus caused by a deficiency of vasopressin. It also has been approved for the treatment of nocturnal enuresis (bed-wetting), which is believed to be caused by an absence of the normal night time rise in vasopressin levels.
Desmopressin is known to cause an increase in both plasma factor VIII (antihemophilic factor) and plasminogen activator. It therefore is approved by the U.S. FDA for use, parenterally and nasally, in reducing spontaneous or trauma-induced bleeding episodes in patients with hemophilia A and type I Von Willebrand's disease, provided that their plasma factor VIII activity is greater than 5%. Stimate, the nasal spray used in treating patients with hemophilia A and type I Von Willebrand's disease, is 15-fold the concentration of DDAVP nasal spray; the latter is used in treating diabetes insipidus.

Safety

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. Symptoms of hyponatremia include nausea, confusion, or altered mental status. 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. 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.

Veterinary Drugs and Treatments

Desmopressin has been found to be useful in the treatment of central diabetes insipidus in small animals. It may be useful in treating Von Willebrand’s disease, but its short duration of activity (2 – 4 hours) in this condition, resistance development, and expense limit its usefulness for this disorder. Desmopressin may be useful perioperatively to reduce lymph node involvement and metastatic disease in canine mammary gland cancer.