Agents that correct hyponatremia by producing a selective water diuresis without affecting sodium and potassium excretion., and urinary free water loss raises serum sodium level.
Include agents tolvaptan and conivaptan.
Indication for these drugs is severe hyponatremia, a serum sodium of 125 mEq/L or less, that s symptomatic, resistant to correction with fluid restriction in patients with SIADH, acute or compensated CHF, or cirrhosis.
Conivaptan is twice as potent as tolvaptan as an inhibitor of V1 receptor, but tolvaptan is 2 1/2 times as potent an inhibitor of the V2 receptor.
Conivaptan is a nonselective vasopressin inhibitor, whereas tolvaptan is a more selective V2 inhibitor.
Conivaptan and tolvaptan are highly protein-bound and metabolized by hepatic cytochrome P-450 isoenzyme CYP3 A4 system,with minimal urinary excretion of less than 5%.
Conivaptan and tolvaptan have a half-life it ranges from 6-10 hours.
Conivaptan is a I potent inhibitor of isoenzyme CYP3A4 limiting its use to a four day intervenous course of administration.
Both drugs increase urine flow and electrolytefree water excretion, without significant changes in sodium or potassium excretion.
The use of vasopressin antagonists associated with the mean increase in plasma sodium level of 4.3 mmol per liter above a control group of placebo treated patients at 3-7 days.
The increase in sodium persists at seven months and efficacy is reported for up to four years.
The efficacy in increasing plasma sodium level is too slow to benefit patients with hyponatremia who have severe cerebral symptoms.
Patients with severe cerebral symptoms and hyponatremia require a prompt decrease in the volume of brain water, best achieved with hypertonic saline.
These agents are ref2242ed to as aquaretic agents.
Vasopressin antagonists are not effective in advanced chronic kidney disease.
Use of these agents consistently increases plasma sodium levels.
At eight hours Tolvaptan has a small increase in sodium level and a 12 hours only half the patients have an increase of more than 4 mmol per liter.
Vasopressin antagonists have no role in the treatment of patients with hyponatremia who have severe CNS symptoms, in whom cerebral edema increases the risk of tentorial herniation.
In patients with hypovolemic hyponatremia volume repletion is required to stop non osmotic release a vasopressin.
Adverse events include: polyuria, urinary frequency, thirst, mouth dryness, nausea and constipation.
The excessive correction of hyponatremia can increase the risk of the osmotic demyelination syndrome.
The use of hypertonic saline and a vasopressin antagonist should be avoided.
15% of patients with hyponatremia do not respond to a vasopressin antagonist and is seen patients in whom urine is not diluted and electrolyte free water is not excreted.