Vasopressin and desmopressin are treatments of choice for pituitary diabetes insipidus. The dosage of desmopressin is 10–40 mcg (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 mcg (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. High-dose vasopressin as a 40-unit intravenous bolus injection may be given to replace epinephrine in the Advanced Cardiovascular Life Support (ACLS) resuscitation protocol for pulseless arrest.
Desmopressin is also used for the treatment of coagulopathy in hemophilia A and von Willebrand disease (see Chapter 34).
Headache, nausea, abdominal cramps, agitation, and allergic reactions occur rarely. Overdosage can result in hyponatremia and seizures.
Vasopressin (but not desmopressin) can cause vasoconstriction and should be used cautiously in patients with coronary artery disease. Nasal insufflation of desmopressin may be less effective when nasal congestion is present.
A group of nonpeptide antagonists of vasopressin receptors has been investigated for use in patients with hyponatremia or acute heart failure, which is often associated with elevated concentrations of vasopressin. Conivaptan has high affinity for both V1a and V2 receptors. Tolvaptan has a 30-fold higher affinity for V2 than for V1 receptors. In several clinical trials, both agents promoted the excretion of free water, relieved symptoms, and reduced objective signs of hyponatremia and heart failure. Conivaptan, administered intravenously, and tolvaptan, given orally, are approved by the FDA for treatment of hyponatremia. Tolvaptan treatment duration is limited to 30 days due to risk of hepatotoxicity, including life-threatening liver failure. Several other nonselective nonpeptide vasopressin receptor antagonists are being investigated for these conditions (see Chapter 15).
Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions
Inhibits production of GH receptors and, to a lesser extent, of TSH, glucagon, insulin, and gastrin Acromegaly and several other hormone-secreting tumors • acute control of bleeding from esophageal varices SC or IV injection • long-acting formulation injected IM monthly • Toxicity: Gastrointestinal disturbances, gallstones, bradycardia, cardiac conduction problems • Lanreotide: Similar to octreotide; available as a long-acting formulation for acromegaly
GONADOTROPINS: FOLLICLE-STIMULATING HORMONE (FSH) ANALOGS •FollitropinalfaActivatesFSHreceptorsMimicseffectsofendogenousFSHControlledovarianstimulation•infertilityduetohypogonadotropichypogonadisminmenSCinjection•Toxicity: Ovarianhyperstimulationsyndromeandmultiplepregnanciesinwomen•gynecomastiainmen•headache,depression,edemainbothsexes
Follitropin beta: A recombinant product with the same peptide sequence as follitropin alfa but differs in its carbohydrate side chains
Urofollitropin: Human FSH purified from the urine of postmenopausal women