Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The European Medicines Agency approved tolvaptan to slow cyst growth and renal failure progression in adults with ADPKD, glomerular filtration 60 mL/min x 1.73 m2 and rapidly progressive disease. In a multicenter 3-year study, conducted on 1,445 patients with non-genotyped ADPKD, ages 18-50 years, predicted creatinine clearance 60 mL/min and kidney total volume 750 mL, tolvaptan slowed kidney failure progression (-23%-46% for different objectives) and reduced kidney volume increase and pain without effects on hypertension and albuminuria.Tolvaptan induced reversible idiosyncratic hepatopathy in 4% of patients (1% in placebo). Tolvaptan antagonizes ADH effects, reduces cyclic-AMP generation in distal nephron, and induces water diuresis. It has high protein-binding and 8-hour half-life. Dosage is 60-120 mg/day in two different doses (for instance 45/15 or 60/30 mg). Treatment starts using lower dose and continues with cautious up-titolation. Data are insufficient for severe hepatopathy or nephropathy. There is no antidote against overdose. Dialysis should not remove tolvaptan. Aquaretic effects require high fluid intake to prevent dehydration. Treatment should be reduced or suspended in case of inadequate fluid intake or dehydration. Weight, natremia and plasma osmolality can inform on dehydration risks. Efficacy is not yet investigated on end-stage renal disease, non-renal ADPKD-related disorders, and mortality.
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PMID:[Treatment of autosomal dominant polycystic kidney disease (ADPKD) - Tolvaptan]. 2779 22

ADH is a hormone secreted by neurohypophysis that plays different roles based on the target organ. At the renal level, this peptide is capable of causing electrolyte-free water absorption, thus playing a key role in the hydro-electrolytic balance. There are pathologies and disorders that jeopardize this balance and, in this field, ADH receptor inhibitors such as Vaptans could play a key role. By inhibiting the activation pathway of vasopressin, they are potentially useful in euvolemic and hypervolemic hypotonic hyponatremia. However, clinical trials in heart failure have not given favourable results on clinical outcomes. Even in SIADH, despite their wide use, there is no agreement by experts on their use. Since vaptans inhibit the cAMP pathway in tubular cells, their use has been proposed to inhibit cystogenesis. A clinical trial has shown favourable effects on ADPKD progression. Because vaptans have been shown to be effective in models of renal cysts disorders other than ADPKD, their use has been proposed in diseases such as nephronophthisis and recessive autosomal polycystic disease. Other possible uses of vaptans could be in kidney transplantation and cardiorenal syndrome. Due to the activity of ADH in coagulation and haemostasis, ADH's activation pathway by Desmopressin Acetate could be a useful strategy to reduce the risk of bleeding in biopsies in patients with haemorrhagic risk.
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PMID:[The pathway of vasopressin as a pharmacological target in nephrology: a narrative review]. 3055 35