Desmopressin intravenous

A 13 kg 3-year-old boy given 40 micrograms of desmopressin intravenously and 1.6 liters of hypotonic fluid over 12 hours had convulsions and a respiratory arrest his plasma sodium fell to 114 mmol/1 (58). 

Desmopressin (DDAVP) increases the release of factor VIII (von Willebrand factor) from endothelial tissue in the vessel wall. Bleeding time is promptly reduced, within 1 hour of administration, and is sustained for 4 to 8 hours.42 Doses used for uremic bleeding are 0.3 to 0.4 mcg/kg intravenously over 20 to 30 minutes, 0.3 mcg/kg subcutaneously, or 2 to 3 mcg/kg intranasally. Repeated doses can cause tachyphylaxis by... 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

Most patients with type 1 vWD (functionally normal vWF) and a minor bleeding episode can be treated successfully with desmopressin, which induces secretion of autologous factor VIII and vWF into plasma. The recommended dose is the same as that used to treat mild factor VIII deficiency (0.3 mcg/kg intravenously in 50 mL of normal saline infused over 15 to 30 minutes). This therapy generally is ineffective in type 2A patients who secrete qualitatively abnormal vWF and is controversial in type 2B patients because it may increase the risk of postinfusion thrombocytopenia. Type 3 vWD patients who lack releasable stores of vWF do not respond to DDAVP therapy.18... 

In vivo Release of Desmopressin and Somatostatin. The in vivo release of Desmopressin and Somatostatin after subcutaneous and intramuscular injections of the peptide in the cubic or the lamellar phase has been studied in the rabbit. Blood was sampled at regular intervals, and systemically absorbed Desmopressin and Somatostatin were determined as the specific immunoreactitvity in plasma of the actual peptide. For details of the analyses with dDAVP, consult ref. 9. For comparison, Desmopressin-like and Somatostatin-like immunoreactitvity (dDAVP-LI and SRIF-LI) in plasma after intravenous bolus injections of the two peptides were determined as well. 

Desmopressin. Desmopressin is an analogue to the endogenous antidiuretic peptide hormone Vasopressin in which the modifications of the N-terminous amino acid and the replacement of the L-Arg for a D-Arg in position 8, significantly increases its biological stability. In this investigation, the half-life of dDAVP in the rabbit after intravenous administration was determined to be approximately 45 minutes. 

Desmopressin can be administered intravenously, subcutaneously, intranasally, or orally. The half-life of circulating desmopressin is 1.5-2.5 hours. Nasal desmopressin is available as a unit dose spray that delivers 0.1 mL per spray it is also available with a calibrated nasal tube that can be used to deliver a more precise dose. Nasal bioavailability of desmopressin is 3-4%, whereas oral bioavailability is less than 1%. 

Intravenous injection is the most common route although subcutaneous injection may also be used. A concentrated nasal spray formulation has been proved to be efficient for home treatment of patients with bleeding episodes or even minor surgical procedures and has also been used prophylacticly (4). The nasal spray used to treat diabetes insipidus (Desmospray) is too dilute for use in disorders of hemostasis. Similarly, desmopressin in tablet form (Desmotabs) is intended for treatment of nocturnal enuresis in children and is of no use in the treatment of hemostatic disorders. 

A 59-year-old man with mild hemophilia A was given a test dose of desmopressin 30 micrograms (0.19 micrograms/kg) in 100 ml of saline by intravenous infusion over 30 minutes (29). Shortly afterwards, having had a cigarette, he developed chest pain. An electrocardiogram showed ST elevation, and a myocardial infarction was confirmed. 

A 3.5-year-old girl with mild hemophilia A received desmopressin 0.3 micrograms/kg intravenously 30 minutes before adenotonsillectomy. She drank 600 ml of fluid within the first 10 hours and then received 300 ml of intravenous 5% dextrose in 0.45% saline. She developed hyponatremia, headache, nausea, and seizures. 

A potential risk of desmopressin is of water intoxication with resultant hyponatremia (48), and rapid falls in serum sodium concentration can result in seizures. The risk is increased in infants and patients receiving hypotonic intravenous fluids, and such patients need to be carefully monitored. 

A 47-year-old woman with von Willebrand disease, who was given desmopressin and intravenous fluids perioperatively, developed hyponatremia and seizures, which resolved after water restriction (50). 

There have been several reports of seizures in association with hyponatremia after intravenous administration of desmopressin to cover surgery in young children with congenital bleeding disorders such as mild hemophilia A or von Willebrand s disease (58-60). Hyponatremia and convulsions have occurred in children without congenital bleeding disorders who received desmopressin for urine concentration tests or to treat nocturnal enuresis (54,61,62). 

Gill JC, Ottum M, Schwartz B. Evaluation of high concentration intranasal and intravenous desmopressin in pediatric patients with mild hemophilia A or mild-to-moderate type 1 von Willebrand disease. J Pediatr 2002 140(5) 595-9. 

Shepherd LL, Hutchinson RJ, Worden EK, Koopmann CF, Coran A. Hyponatremia and seizures after intravenous administration of desmopressin acetate for surgical hemostasis. J Pediatr 1989 114(3) 470-2. 

Desmopressin Acetate. Desmopressin acetate (DDAVP.Slimale)is.synthetic l-dcsnmino-8-ivargininc va-mpressin. Ils efficacy, ease of administration (intranasal). long duration of action, and lack of side effects make il the dnig of choice for ihe treat meni of central diabetes insipidus. It may al.so be administered intramuscularly or intravenously. Il is preferred lo va.sopressin injection and oral anti-... 

Desmopressin may be administered intranasaUy via a concentrated nasal spray. It effectively increases factor VIE levels, but its peak eEect occurs 60 to 90 minutes after administration, somewhat longer than with desmopressin administered intravenously. The dosage is one spray (150 meg) for children who weigh less than 50 kg and two sprays (300 meg) for those who weigh more than 50 kg. The nasal spray may serve as an altemative to the intravenous formulation, especially in patients with nuld bleeding episodes. 

The dose of desmopressin for von WiUebrand disease is identical to that used in the treatment of mild factor VIII deficiency, 0.3 mcg/kg diluted in 30 to 50 mL of normal saline and given intravenously over 15 to 30 minutes. In general, patients with von WiUebrand disease have a better response to desmopressin than those with hemophilia, with an average three- to fivefold rise in von WiUebrand factor and factor VIII levels. These levels remain elevated for about 6 to 8 hours. The response to desmopressin in a given patient is usuaUy consistent, and a trial of desmopressin should establish if the medication is likely to be effective for the individual. Desmopressin is preferable to the use of plasma-derived products for patients who have an adequate response because desmopressin does not carry a risk of viral transmission. An added benefit is that desmopressin is substantiaUy less costly than the plasma-derived products. (For a discussion of the side effects of desmopressin, see the section on the treatment of hemophUia A.)... 

Only two antidiuretic peptides are available for clinical use in the United States (1) Vasopressin (synthetic 8-l-arginine vasopressin Pitressin) is available as a sterile aqueous solution it may be administered subcutaneously, intramuscularly, or intranasally. (2) Desmopressin acetate (synthetic l-deamino-8-D-arginine vasopressin DDAVP, others) is available as a sterile aqueous solution packaged for intravenous or subcutaneous injection, in a nasal solution for intranasal administration with either a nasal spray pump or rhinal tube delivery system, and in tablets for oral administration. The therapeutic uses of vasopressin and its congeners can be divided into two main categories according to the type of vasopressin receptor involved. 

Vasopressin is administered parenterally, but its synthetic analog, desmopressin acetate, can be administered by rhinal tube or orally, by tablet, for the treatment of diabetes insipidus [10]. Oxytocin and Vasopressin are manufactured through solid-phase synthesis [22, 23]. Antidiuretics are in fairly widespread use, having been prescribed in about 15% of all physician visits in the United Sates in 2002-2003 up from about 10% only 7 years before [24]. Oxytocin is used to induce labor by parenteral administration, either through subcutaneous or intravenous injection, or can be administered nasally to increase milk production in nursing mothers. Oxytocin induction of labor occurred in approximately 20% of births in the United States in 2003 [24]. 

As another parameter to alter the pharmacodynamic prohle of desmopressin, a sex difference is most important. In 2004, Odeberg et al. demonstrated that there was a sex difference in a human pharmacokinetic (PK) and pharmacodynamic (PD) study [214], where desmopressin was administered intravenously as a single dose (for the PK study, a 2-pg dose for the PD study, a 0.2-pg dose), and parameters for urine flow and urine osmolality were estimated. The pharmacokinetics of desmopressin after a fixed bofus injection were influenced neither by piroxicam nor by sex of subjects. However, the pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically signihcant when the effects were submaximal (>4.5h after dose). The sex differences were diminished after pretreatment with an NSAID, piroxicam, indicating a prostaglandin PGE2-mediated mechanism. 

Rembratt A, Grangaard-Jensen C, Senderovitz T, et al. (2004). Pharmacokinetics and pharmacodynamics of desmopressin administred orally versus intravenously at daytime versus night-time in healthy men aged 55-70 years. Eur. J. Clin. Pharmacol. 60 397-402. 

Lethagen S, Harris A S, Sjorin E, et al. (1987). Intranasal and intravenous administration of desmopressin Effect on F VIII/vW, pharmacokinetics and reproducibility. Thromb. Haematost. 58 1033-1036. 

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