DESMOPRESSIN ACETATE

Chemistry - A synthetic polypeptide related to arginine vasopressin (antidiuretic hormone), desmopressin acetate occurs as a fluffy white powder having a bitter taste. The commerciallyavailable nasal solution has HCl added and the pH is approximately 4. This preparation alsocontains chlorobutonal 0.5% as a preservative.

Storage, Stability, Compatibility

The nasal solution should be stored in the refrigerator (2-8°C). It has an expiration date of one year after manufacture. While the nasal solution should be stored in the refrigerator, it is stable at room temperature for 3 weeks in the unopened bottle. The product for injection should be stored refrigerated (4°C); do not freeze.

Pharmacology - DESMOPRESSIN ACETATE

Desmopressin is related structurally to arginine vasopressin, but it has moreantidiuretic activity and less vasopressor properties on a per weight basis. Desmopressin increaseswater reabsorption by the collecting ducts in the kidneys, thereby increasing urine osmolality anddecreasing net urine production. Therapeutic doses do not directly affect either urinary sodium orpotassium excretion.
Desmopressin also causes a dose-dependent increase in plasma factor VIII and plasminogenfactor. It also causes smaller increases in factor VIII-related antigen and ristocetin cofactor activities.
Uses, Indications - Desmopressin has been found to be useful in the treatment of central diabetesinsipidus in small animals. It may be useful in treating Von Willebrand's disease, but its shortduration of activity (2-4 hours) in this condition, resistance development, and expense limit itsusefulness for this disorder.

Pharmacokinetics - DESMOPRESSIN ACETATE

Because desmopressin is destroyed in the GI tract, it must be given parenterally or topically. In humans, intranasal administration is commonly used, while in veterinary medicine topical administration to the conjunctiva is preferred. The onset of antidiuretic action in dogs usually occurs within one hour of administration, peaks in 2-8 hours and may persist for up to 24 hours. Distribution characteristics of desmopressin are not well described, but it does enter maternal milk. The metabolic fate is also not well understood. Terminal half lives in humans after IV administration are from 0.4 - 4 hours.

Contraindications, Precautions, Reproductive Safety

Desmopressin is contraindicated in patients hypersensitive to it. It should not be used for treatment of type IIB or platelet-type (pseudo)
Von Willebrand's disease as platelet-aggregation and thrombocytopenia may occur. German shorthair pointers apparently can have this type of vWD. Desmopressin should be used with caution in patient's susceptible to thrombotic events.
Safe use during pregnancy has not been established; however safe doses of up to 125 times the average human antidiuretic dose have been given to rats and rabbits without demonstration of fetal harm.

Adverse Effects, Warnings

Side effects in small animals apparently are uncommon.
Occasionally eye irritation may occur after conjunctival administration. Hypersensitivity reactions are possible. Humans using the drug have complained about increased headache frequency.

Overdosage, Acute Toxicity

Dosages that are too high may lead to fluid retention and hyponatremia. Dosage reduction and fluid restriction may be employed to treat. Adequate monitoring should be performed.

Drug Interactions

Chlorpropamide, carbamazepine, clofibrate, fludrocortisone, or ureamay enhance the antidiuretic effects of desmopressin. Lithium, large doses of epinephrine, demeclocycline, heparin or alcohol may decrease the antidiuretic effects of desmopressin.
Laboratory Considerations - See Monitoring Parameters