Desmopressin administration

Convulsions have been reported after desmopressin administration, some associated with excessive fluid intake. 

Insignificant quantities of desmopressin pass into breast milk (74), and so breastfeeding is not contraindicated in association with desmopressin administration to a nursing mother. 

D Alauro FS, Johns RA. Hypotension related to desmopressin administration following cardiopulmonary bypass. Anesthesiology 1988 69(6) 962-3. 

Grunwald Z, Sather SD. Intraoperative cerebral infarction after desmopressin administration in infant with end-stage renal disease. Lancet 1995 345(8961) 1364-5. 

Francis JD, Leary T, Niblett DJ. Convulsions and respiratory arrest in association with desmopressin administration for the treatment of a bleeding tonsil in a child with borderline haemophilia. Acta Anaesthesiol Scand 1999 43(8) 870-3. 

Sun HL, Chien CC. Thrombocytopenia and subdural hemorrhage after desmopressin administration. Anesthesiology 1998 88(4) 1115-7. 

Overman M, Brass E. Worsening of thrombotic thrombocytopenic purpura symptoms associated with desmopressin administration. Thromb Haemost 2004 92 886-7. 

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. 

In central diabetes insipidus a hypophysial malfunction, caused by different diseases as well as head injuries, neurosurgery, or genetic disorders, leads to AVP hyposecretion. This type of diabetes insipidus can successfully be treated by the exogenous administration of AVP or AVP analogues (e.g. desmopressin). 

Syndrome of inappropriate antidiuretic hormone is defined by water retention, dilutional hyponatraemia and decreased volume of highly concentrated urine. There are several causes which can result in SIADH, neoplasms ectopic secreting AVP, ectopic release of AVP by various diseases or drugs, exogenous administration of AVP, desmopressin, lysipressin or large doses of OT (iatrogenic SLADH). 

Desmopressin may be given orally, intranasally, SC, or IV. The oral dose must be determined for each individual patient and adjusted according to the patient s response to therapy. When the drug is administered nasally, a nasal tube is used for administration. The nasal tube delivery system comes with a flexible calibrated plastic tube called a rhinyle. The solution is drawn into the rhinyle. One end is inserted into the nostril and the patient (if condition allows) blows the other end to deposit solution deep into the nasal cavity. A nasal spray pump may also be used. Most adults require 0.2 mL daily in two divided doses to control diabetes insipidus. The drug may also be administered via the SC route or direct IV injection. 

Educating the Patient and Family If lypressin or desmopressin is to be used in the form of a nasal spray or is to be instilled intranasally usingthe nasal tube delivery system, the nurse demonstrates the technique of instillation (see Fhtient and Family Teaching Checklist Self-Adnrinistering Nasal Vasopressin). The nurse includes illustrated patient instructions with the drug and reviews them with the patient. If possible, the nurse lias the patient demonstrate the technique of administration. The nurse should discuss the need to take the drug only as directed by the primary health care provider. The patient should not increase the dosage (ie, the number or frequency of sprays) unless advised to do so by the primary health care provider. 

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... 

The individual responsiveness to desmopressin is consistent, and a test dose administered at the time of diagnosis or prior to therapy is the best predictor of response. Generally, DDAVP is more effective in vWD than in hemophilia patients, with an average 30% to 50% increase in vWF and factor VIII levels. In patients with an adequate response, desmopressin is first-line therapy because it allows for once-daily administration (elevates plasma levels for 8-10 hours), does not pose a threat in terms of viral transmission, and the cost is substantially less than that of the plasma-derived products. Fibrinolysis inhibitors (50-60 mg/kg of aminocapriotic acid every 4—6 hours or trenex-amic acid 10-15 mg/kg every 8-12 hours) and OCs are used successfully in the management of epistaxis and menorrhagia or as adjuvant treatments. 

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. 

Peptide/protein uptake rates across the nasal epithelia are dependent upon molecular mass. Relatively small peptides, such as oxytocin, desmopressin and LHRH analogues, cross relatively easily and several such products used medically are routinely delivered nasally. Larger molecules (of molecular mass greater than 10 kDa) generally do not cross the epithelial barrier without the concurrent administration of detergent-like uptake enhancers. Long-term use of enhancers is prohibited due to their damaging cellular effects. 

Administration of an AVP analog, such as desmopressin acetate (DDAVP), can produce a 30% to 60% reduction in wet nights in general, and about a 50% resolution of enuresis while on the medication (Norgaard et ah, 1985 Klauber, 1989 Norgaard et al.. 

Oral administration of 0.1-0.2 mg desmopressin provides an antidiuretic effect lasting for 8-12 hours. Desmopressin does not cross blood brain barrier and maximal plasma concentrations are reached within 2 hours. After oral administration, varies between 2.0 hours and 3.2 hours. 65% of oral desmopressin absorbed is excreted unchanged in the urine. It is also used as a nasal spray. 

Vasopressin and desmopressin are treatments of choice for pituitary diabetes insipidus. The dosage of desmopressin is 10-40 meg (0.1-0.4 mL) in two to three divided doses as a nasal spray or, as an oral tablet, 0.1-0.2 mg two to three times daily. The dosage by injection is 1-4 meg (0.25-1 mL) every 12-24 hours as needed for polyuria, polydipsia, or hypernatremia. Bedtime desmopressin therapy, by intranasal or oral administration, ameliorates nocturnal enuresis by decreasing nocturnal urine production. Vasopressin infusion is effective in some cases of esophageal variceal bleeding and colonic diverticular bleeding. 

The pharmacokinetics of one dose of desmopressin 400 micrograms have been investigated in 15 men and nine women with nocturia aged over 65 years (40). They then entered a placebo-controlled crossover evaluation period. Peak concentrations occurred at 1-2 hours after administration and gradually fell over 6-7 hours. The women had significantly higher concentrations than the men, even after adjustment for body weight. Four women were withdrawn from the crossover period because of hyponatremia. 

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). 

Pulmonary edema associated with fluid retention occurred in a 27-year-old man after the administration of desmopressin to reduce blood loss during surgery (63). 

In four patients with von Willebrand disease, desmopressin caused a significant but transient reduction in platelet count without an increase in plasma glycocalicin concentrations nor enhanced expression of P selectin, suggesting that acute thrombocytopenia after the administration of desmopressin in type 2B von Willebrand disease is not related to platelet activation and consumption (68). 

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. 

---