Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardial infarction is associated with complex neuroendocrine changes, including release of arginine vasopressin, norepinephrine, and epinephrine, and activation of the renin-angiotensin system. Arginine vasopressin levels are maximal on admission, and subsequently fall even in patients in whom left ventricular failure develops. Plasma levels of norepinephrine and epinephrine are at their highest on admission and return to the normal range in patients with uncomplicated infarction, but they remain significantly elevated in patients in whom left ventricular failure or late ventricular arrhythmias develop. In contrast to catecholamines and arginine vasopressin, plasma renin and angiotensin levels are within normal limits on admission in patients without complications but increase by the third day. Patients with left ventricular failure already have increased plasma levels of renin and angiotensin on admission, but further marked and persistent increases occur over the following days. All of the aforementioned hormones may interact to cause systemic or coronary vasoconstriction, which may have short-term adverse hemodynamic consequences. Furthermore, increased afterload may result in infarct expansion and left ventricular dilatation, which will impair left ventricular function still further. Interruption of the cycle of vasoconstriction and worsening left ventricular failure by angiotensin converting enzyme inhibitors may reduce the incidence of heart failure after myocardial infarction.
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PMID:Neuroendocrine changes in acute myocardial infarction. 306

Tolvaptan is a selective arginine vasopressin (AVP) V(2) receptor blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic hyponatremia. Currently the orally active medication is in the final stages prior to approval by the FDA for outpatient therapy. It appears to be safe and effective at promoting aquaresis and raising serum sodium levels in both short- and long-term studies. Tolvaptan is also effective for treatment of congestive heart failure (CHF) exacerbation, but whether there are long standing beneficial effects on CHF is still controversial. Prolonged use of tolvaptan leads to increased endogenous levels of AVP and perhaps over-stimulation of V(1A) receptors. Theoretically this activation could lead to increased afterload and cardiac myocyte fibrosis, causing progression of CHF. However, after 52 weeks of tolvaptan therapy there was no worsening of left ventricular dilatation. In addition, tolvaptan is metabolized by the CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications. Tolvaptan is a breakthrough in the therapy of hyponatremia as it directly combats elevated AVP levels associated with the syndrome of inappropriate secretion of antidiuretic hormone, congestive heart failure, and cirrhosis of the liver.
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PMID:Tolvaptan and its potential in the treatment of hyponatremia. 1933 22