Antidiuretic hormone antagonists

Antidiuretic hormone antagonists inhibit the effects of ADH in the collecting tubule. Conivaptan is a pharmacologic antagonist at Via and V2 receptors. Both lithium and demeclocycline appear to reduce the formation of cyclic adenosine monophosphate (cAMP) in response to ADH. 

Antidiuretic hormone antagonists are used to manage SIADH when water restriction has failed to correct the abnormality. This generally occurs in the outpatient setting, where water restriction cannot be enforced, or in the hospital when large quantities of intravenous fluid are needed for other purposes. Lithium carbonate has been used to treat this syndrome, but the response is unpredictable. Demeclocycline, in dosages of 600-1200 mg/d, yields a more predictable result and is less toxic. Appropriate plasma levels (2 mcg/mL) should be maintained by monitoring. Unlike demeclocycline, conivaptan is administered by IV injection, so it is not suitable for chronic use in outpatients. Lixivaptan and tolvaptan should soon be available for oral use. 

Enhancement of diuretic hormone actions could be fatal for those insects that have critical problems of maintaining body water, esp. soft-bodied larvae. Soft-bodied larvae rely on hemolymph volume to maintain turgor for movement, and dehydration would result in immobility followed by death, inhibition of antidiuretic hormones could have serious effects on insects that reside in extremely dry environments, e.g. stored grain. Antidiuretic hormone antagonists in combination with diuretic hormone agonists would be especially potent. 

A vasopressin V2 receptor antagonist, lixivaptan, is currently being developed (Phase 11) for the treatment of hyponatremia. This agent blocks the effect of the antidiuretic hormone arginine-vasopressin. 

Doses from/with smoking. Nicotine causes release of catecholamines in the CNS, also serotonin, and antidiuretic hormone, corticotrophin and growth hormone. The effects of nicotine on viscera are probably largely reflex, from stimulation of sensory receptors (chemoreceptors) in the carotid and aortic bodies, pulmonary circulation and left ventricle. Some of the results are mutually antagonistic. 

Guyader, D., Patat, A., Ellis-Grosse, E.J., Orczyk, G.P. Pharmacodynamic effects of a nonpeptide antidiuretic hormone V2 antagonist in cirrhotic patients with ascites. Hepatology 2002 36 1197-1203... 

Saito T, IshikawaS, Abe K, et al. Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Clin Endocrinol Metab 1997 82 1054-1057. 

Alkaloid a-adrenergic receptor antagonist. Vasodilator said to be an aphrodisiac. Local anaesthetic about as potent as cocaine. Releases antidiuretic hormone from posterior pituitary. Related to reserpine. 

Satavaptan [36], a vasopressin V2 receptor antagonist was developed as a potential treatment for hyponatremia in syndrome of inappropriate secretion of antidiuretic hormone (SIADH, Schwartz-Bartter syndrome) and cirrhotic ascites. However, by Febmary 2009, development was terminated for both indications. 

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. 

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