Vasopressin antidiuretic effect

Vasopressin (antidiuretic hormone [ADH]) secretion increases in response to decreased blood volume and/or reductions in effective blood volume via a decrease in inhibitory tone from both low-pressure and high-pressure baroreceptors to the hypothalamus. The neuronal pathways that mediate hemodynamic regulation of... 

The antidiuretic effects of vasopressin may be decreased when die agent is taken witii die following drugs lithium, heparin, norepinephrine, or alcohol. Antidiuretic effect may be increased when die drug is used witii carbamazepine, clofibrate, or fludrocortisone... 

Nephrogenic diabetes insipidus (NDI) is characterized by renal tubular resistance to the antidiuretic effect of arginine vasopressin (AVP). NDI may be inherited as an autosomal dominant or X-linked recessive disorder. The autosomal dominant form of NDI results from mutations of the aquaporin 2 gene (AQP2). AQP2 encodes a water channel of the renal collecting duct. Its disruption causes autosomal dominant NDI (113,114) and occasionally recessive forms of the disease. 

Adverse reactions to carbamazepine include nystagmus, ataxia, diplopia, particularly if the dosage is raised too fast. Gastrointestinal problems and skin rashes are frequent It exerts an antidiuretic effect (sensitization of collecting ducts to vasopressin water intoxication). 

Because its vasoconstrictor effects limit the use of the native hormone, analogues with greater or lesser affinity for vasopressin V2 receptors and more selective antidiuretic effects have been developed ... 

Oxytocin is used in obstetrics to induce labor, e.g. to maintain the uterine contractions during birth, and to promote the evacuation of milk. The most important therapeutic use of vasopressin is based on its antidiuretic effect in diabetes insipidus (e.g. l-desamino-D-Arg8-vasopressin as a nasal spray92 ). 

Bode U, Seif SM, and Eevin AS. Studies on the antidiuretic effect of cyclophosphamide vasopressin release and sodium excretion. Med Pediatr Oncol 8 295-303,1980... 

B. Aniline Derivatives - A structure-activity study of a new series of alkoxyaniline derivatives has been reported along with a detailed workup of one of them . This compound (XII) appears to have good analgesic and anti-inflammatory activity, associated with some CNS depressant effects. An antidiuretic effect was described for acetaminophen 9 a d it was suggested that this drug might be a useful substitute for vasopressin in certain patients with diabetes insipidus. Evidence was also presented to show that acetophenetidin has antipyretic activity which is not dependent on metabolism to N-acetyl-p-aminophenol. 

Chlorpromazine may have weak diuretic effects because of a depressant action on the secretion of vasopressin (antidiuretic hormone, ADH), inhibition of reabsorption of water and electrolytes by a direct action on the renal tubule, or both. The syndrome of idiopathic polydipsia and hyponatremia sometimes associated with psychotic illness has respotuled to clozapine, presumably via... 

Alcohol inhibits the release of vasopressin (antidiuretic hormone see Chapter 29) from the posterior pituitary gland, resulting in enhanced diuresis. The volume loading that accompanies imbibing complements the diuresis that occurs as a result of reduced vasopressin secretion. Alcoholics have less urine output than do control subjects in response to a challenge dose with ethanol, suggesting that tolerance develops to the diuretic effects of ethanol. Alcoholics withdrawing from alcohol exhibit increased vasopressin release and a consequent retention of water, as well as dilutional hyponatremia. 

A number of drugs inhibit the antidiuretic actions of vasopressin. Lithium is of particular importance because of its use in the treatment of manic-depressive disorders. Lithium-induced polyuria is usually reversible. Acutely, lithium appears to reduce V -receptor-mediated stimulation of adeny-lyl cyclase. Also, hthium increases plasma levels of parathyroid hormone, a partial antagonist to vasopressin. In most patients, the antibiotic demeclocycline attenuates the antidiuretic effects of vasopressin, probably owing to decreased accumulation and action of cyclic AMP. 

PHARMACOKINETICS When vasopressin and desmopressin are given orally, they are rapidly inactivated by trypsin, which cleaves the peptide bond between amino acids 8 and 9. Inactivation by peptidases in various tissues (particularly the Uver and kidneys) results in a plasma tj of vasopressin of 17-35 minutes. Following intramuscular or subcutaneous injection, the antidiuretic effects of vasopressin last 2-8 hours. The plasma t of desmopressin has a fast component of 6.5-9 minutes and a slow component of 30-117 minutes. Only 3% and 0.15%, respectively, of intranasaUy and orally administered desmopressin is absorbed. 

The major receptor-mediated adverse effect is water intoxication, which can occur with desmopressin or vasopressin. Many drugs, including carbamazepine, chlorpropamide, morphine, tricyclic antidepressants and NSAIDs, can potentiate the antidiuretic effects of these peptides, while lithium, demeclocycline and ethanol can attenuate the antidiuretic response to desmopressin. Desmopressin and vasopressin should be used cautiously when a rapid increase in extracellular water may impose risks (e.g., in angina, hypertension, and heart failure) and should not be used in patients with acute renal failure. Patients receiving desmopressin to maintain hemostasis should be... 

B. Vasopressin (Antidiuretic Hormone, ADH) Vasopressin is synthesized in the supraoptic nuclei of the hypothalamus and released from the posterior pituitary. As discussed in Chapter 15, vasopressin acts on V2 receptors and increases the synthesis or insertion of water channels by a cAMP-dependent mechanism, resulting in an increase in water permeability in the collecting tubules of the kidney. The increased water permeability permits water reabsorption into the hypertonic renal papilla, thus causing the antidiuretic effect. Vasopressin also causes smooth muscle contraction (a V, effect). Desmopresan, a selective agonist of V2 receptors, is used in the treatment of pituitary diabetes insipidus. 

The posterior pituitary releases two hormones, oxytocin and vasopressin. Oxytocin induces contractions in the gravid uterus and is therefore used when labor acceleration is desired. Because it is chemically similar to vasopressin, oxytocin has antidiuretic effects and can cause fluid retention. Oxytocin and other uterine contractants and relaxants are listed in Table 10.3. 

Vasopressin stimulates reabsorption of water by the kidney, thus having an antidiuretic effect. More water is retained, and the blood pressure increases. 

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