Chapter 12: Clinical Use of the Vasopressin Analog Desmopressin for the Diagnosis and Treatment of Diabetes Insipidus

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Clinical Use of the Vasopressin Analog Desmopressin for the Diagnosis and Treatment of Diabetes Insipidus





Background


Primary disorders of water balance such as central diabetes insipidus, primary nephrogenic diabetes insipidus, and primary polydipsia, although uncommon, should always be considered in the differential diagnosis of polyuria and polydipsia. The water deprivation test is generally considered the best diagnostic tool for differentiating between these disorders. However, the test is labor intensive, difficult to perform correctly, and unpleasant for the animal; relies heavily on repeated emptying of the bladder; and can lead to untoward complications and misdiagnosis in some animals. As an alternative to water deprivation testing, a simpler and more practical method of diagnosis is evaluation of the clinical response to a closely monitored therapeutic trial with desmopressin (DDAVP, Stimate, Minirin). Desmopressin is a synthetic analog of the natural antidiuretic hormone arginine vasopressin (ADH), which has increased antidiuretic activity, prolonged duration of action, decreased pressor actions, and fewer side effects than the natural hormone. Historically, if a diagnosis of central diabetes insipidus was confirmed, ADH tannate in oil, an extract of natural antidiuretic hormone prepared from bovine and porcine pituitary glands, was administered every 2 to 3 days as needed to control polyuria and polydipsia. Because the product is no longer available, desmopressin has become the drug of choice for the treatment of central diabetes insipidus in dogs and cats.



Desmopressin Preparations


Desmopressin is available in proprietary, generic, and compounded preparations for intranasal, ophthalmic, parenteral (injectable), or oral administration.



Nasal and Ophthalmic Solutions of Desmopressin


The nasal formulations are supplied by two different delivery systems: via either a spray pump or a rhinal tube, with the desmopressin sprayed or “blown” into the nose, respectively. Obviously, most dogs and cats will not tolerate either of these intranasal delivery methods. Drops placed in the conjunctival sac provide a more suitable alternative for animals.


With the rhinal tube delivery formulation (DDAVP Rhinal Tube), the desmopressin is packaged with a small, calibrated plastic catheter so that exact amounts of the drug can be measured and administered. The calibrated rhinal tube has four graduation marks that measure amounts of 0.05 ml, 0.1 ml, 0.15 ml, and 0.2 ml and thereby can deliver doses of 5 to 20 µg of desmopressin. Although this system allows for accurate dosing, it is awkward to use. In addition, because this rhinal tube delivery system is not available as a generic product, this formulation is quite expensive.


The most common intranasal formulations of desmopressin are marketed as nasal sprays or solutions equipped with a compression pump that delivers 10 µg of drug with each spray. For dogs and cats, this spray bottle is opened (pliers may be necessary to break the seal) and the desmopressin solution is transferred to a sterile vial; this dispensing vial then allows one to place the desmopressin drops into the animal’s conjunctival sac.


These intranasal preparations of desmopressin are generally supplied as a concentration of 100 µg/ml; depending on drop size, one drop of nasal solution corresponds to 1.5 to 4 µg of desmopressin. One highly concentrated nasal solution (1.5 mg/ml) is marketed for use in type I von Willebrand’s disease and hemophilia, but it should not be used to treat animals with diabetes insipidus because of the strong likelihood of overdose.


In most cats and small dogs, 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia. Larger dogs may require up to 4 to 5 drops twice daily. Use of a tuberculin or insulin syringe allows for more accurate dosing.


As an alternative to the intranasal preparation, some compounding pharmacies offer a sterile ophthalmic solution (100 µg/ml) that costs considerably less than the intranasal product. In addition to its cost and convenience, the ophthalmic solution is buffered to a neutral pH, whereas the intranasal form is acidic and may cause local irritation. However, even without issues of local irritation, some animals may object to the daily eyedrops, making this route of administration ineffective.



Oral Desmopressin Tablets, Flavored Chews and Suspensions


The proprietary and generic oral preparations of desmopressin are available both as a sublingual dissolve melt tablet and as 0.1 mg and 0.2 mg tablets. In addition, flavored oral chews and suspensions are available from compounding pharmacies. Each 0.1 mg (100 µg) tablet or chew is roughly comparable to 5 to 10 µg (1 to 2 large drops) of the nasal or ophthalmic solutions; the concentration of the flavored suspensions may vary. When comparing the cost of the proprietary forms of desmopressin, the tablet form is a more cost-prohibitive alternative compared with the conjunctival or subcutaneous routes of administration. The cost of daily oral desmopressin in animals is roughly 2.5 times that of conjunctival drops and roughly 6 times that of subcutaneous injections of desmopressin. By comparison, the cost of generic tablets and compounded flavored chews and suspensions is roughly equal to the cost of compounded ophthalmic and injectable preparations. For some pet owners a tablet, chew, or suspension may prove to be a more convenient, or the only possible, route of administration.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 12: Clinical Use of the Vasopressin Analog Desmopressin for the Diagnosis and Treatment of Diabetes Insipidus

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