- treatment of hyponatremia
- alternative or addition to fluid restriction and sodium chloride administration
- vasopressin receptors:
- V2: antidiuretic response
- V1a: vasoconstriction
- V1b: adrenocorticotropic hormone release
- selective free water diuresis (aquaresis) -- do not affect excretion of sodium or potassium
- increased urine output
- decreased urine osmolality
- restoration of serum sodium levels
- increases thirst significantly - limits sodium rise
- oral -- selective V2: tolvaptan (29:1 ratio, V2:V1a)
- IV -- blocks V2 and V1a: conivaptan
- tolvaptan: warnings -- should not be used longer than 30 days -- risk of hepatotoxicity, should not be used in liver disease
- conivaptan: concerns with V1a block leading to hypotension and increased risk of variceal bleeding in cirrhosis patients (vasopressin is used to treat active bleeds), also may worsen renal function in cirrhosis patients -- terlipressin (V1a agonist to treat hepatorenal syndrome)
- have been studied in hyponatremia due to SIADH, heart failure, and cirrhosis
- should NOT be used in patients who are hyponatremic and volume depleted (repletion with saline is primary therapy)
- do not correct sodium too quickly --> osmotic demyelination of nerves
- no more than 8 mEq/L in 8 hours or 12 mEq/L in 24 hours
- slower rates in malnutrition, alcoholism, advanced liver disease
- only initiate in hospital setting to monitor serum levels
- adverse effects: increased thirst, dry mouth, polyuria
- substrate of cyp3A4 = many DDI's
- monitoring: serum sodium, rate of sodium increase, serum potassium, volume status, signs of hepatotoxicity/ hepatic function test
- half-life ~ 12 hours
- onset of action 2-4 hours, peak at 4-8 hours
- cost:
- 15 mg tablets (wty: 10) = $4293.70
Wednesday, November 23, 2016
vasopressin receptor antagonists
Vasopressin (ADH) Receptor Antagonists
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