Syndrome of Inappropriate Antidiuretic Hormone Secretion Medication
- Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Vasopressin receptor antagonists inhibit the V2 receptor, reducing the number of aquaporin-2 water channels in the renal collecting duct and decreasing the water permeability of the collecting duct.
The use of a combination of a loop diuretic (eg, furosemide) and the replacement of urine output with a solution that contains a higher Na+ concentration (ie, 3% sodium chloride solution) can be dramatically successful in some patients. Concomitant use of furosemide increases free water excretion relative to Na+ excretion by the kidneys, thus correcting fluid expansion induced by hypertonic sodium chloride solution.
The potential benefits of these drugs include the predictability of their effect, rapid onset of action, and limited urinary electrolyte excretion. Conivaptan and tolvaptan are currently the only vasopressin receptor antagonists that are commercially available in the United States and FDA-approved for the treatment of euvolemic hyponatremia in hospitalized patients. These medications should be initiated in a closely monitored setting to prevent rapid correction of serum Na+, which can result in central pontine myelinolysis (CMP).
Conivaptan is a parenteral nonselective vasopressin receptor antagonist used for the treatment of euvolemic hyponatremia in hospitalized patients. Conivaptan increases urine output of mostly free water, with little electrolyte loss. It is indicated for hospitalized patients with more severe euvolemic or hypervolemic hyponatremia.
Tolvaptan is an oral selective vasopressin V2-receptor antagonist. It is indicated for hypervolemic and euvolemic hyponatremia (ie, serum Na level < 125 mEq/L) or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction. It is used for hyponatremia associated with CHF, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Initiate or reinitiate the drug in a hospital environment only since there may be overly rapid correction of the hyponatremia. However, it increases thirst (potentially limiting its effects) and is expensive.
These agents are often used in the treatment of hypervolemic hyponatremia. In patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) with euvolemic hyponatremia, diuretics are usually used in conjunction with normal saline to replenish the Na+ excreted with the diuresis.
Furosemide increases excretion of water by interfering with the Na+-K+-Cl- (Na-K-2Cl) transporter; that, in turn, results in inhibition of Na+ and Cl- reabsorption in the ascending loop of Henle. Na+ is reabsorbed more distally and the excreted urine is hypo-osmolar in relation to serum.
Diuretics, Osmotic Agents
These agents induce diuresis by elevating the osmolarity of the glomerular filtrate, thereby hindering the tubular reabsorption of water. The overall effect is an increase in free water excretion by the kidneys. Concomitantly, Na+ and Cl- excretion also increase, but to a lesser extent than water excretion.
Urea is used for the treatment of SIADH refractory to or in patients noncompliant with other therapies or when other therapies are not available. Urea is known to promote diuresis. It decreases brain edema, restores medullary tonicity, and induces Na+ retention. Isosmotic concentration of dextrose or invert sugar is coadministered with urea to prevent hemolysis produced by pure solutions of urea.
Mannitol promotes a rapid free-water diuresis by elevating the osmolarity of the glomerular filtrate, thereby hindering the tubular reabsorption of water. Concomitantly, Na+ and Cl- excretion also increase but to a lesser extent than water excretion. It is typically used intravenously, as a 15-20% solution.
Demeclocycline is an older tetracycline. One of its adverse effects is nephrogenic diabetes insipidus and polyuria, which can correct the excess of water seen in SIADH. It is no longer available in most countries and may be nephrotoxic in patients with liver failure.
Demeclocycline is a tetracycline derivative that induces diabetes insipidus by impairing the generation and action of cAMP, thus interfering with the action of AVP on the collecting duct. The drug's onset of action may be delayed by over a week; thus, it is not indicated for the emergency management of symptomatic hyponatremia.
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