Drugs online research references
Gut. 1980 Oct;21(10):855-9.
Use of piretanide, a new loop diuretic, in cirrhosis with ascites: relationship between the diuretic response and the plasma aldosterone level.
Arroyo V, Bosch J, Casamitjana R, Cabrera J, Rivera F, Rodes J.
Twenty patients with cirrhosis and ascites but no renal failure were given piretanide, a new loop diuretic, in order to investigate its efficacy and to relate the diuretic response with the pretreatment plasma aldosterone concentration. Eleven patients responded to piretanide 12 mg/day (equivalent in potency to 80 mg furosemide); there was no response in nine patients. Both groups were similar with regard to liver function, plasma urea, serum creatinine, plasma electrolytes, urine volume, and urine potassium concentration. The basal urinary sodium excretion was significantly higher in those patients who responded (23.6 +/- 5.7 mmol/day vs. 4.3 +/- 1.42 mmol/day; P < 0.01) (M +/- SE). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were normal or only slightly increased in patients who responded to piretanide (PRA = 1.22 +/- 0.20 ng/ml/h; PAC = 12.25 +/- 2.20 ng/100 ml) and very high in patients who did not respond (PRA = 8.71 +/- 1.18 ng/ml/h; PAC = 84.6 +/- 16.2 ng/100 ml) (P < 0.001). Patients unresponsive to piretanide 12 mg/day also failed to respond when the dose was increased to 24 mg/day. However, the addition of spironolactone, 150 mg/day, to piretanide was followed in these patients by a marked increase in diuresis and natriuresis. These results strongly suggest that the pre-treatment level of aldosterone is an important factor influencing the response to loop diuretics in patients with non-azotaemic cirrhosis and ascites.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7439805&dopt=Abstract
J Cardiovasc Pharmacol. 1989 Aug;14(2):221-6.
CGP 38 560: orally active, low-molecular-weight renin inhibitor with high potency and specificity.
Wood JM, Criscione L, de Gasparo M, Buhlmayer P, Rueger H, Stanton JL, Jupp RA, Kay J.
Research Department, Ciba-Geigy, Basel, Switzerland.
CGP 38 560 is a low-molecular-weight (730) inhibitor of human renin that contains only one natural amino acid. In vitro, it is a potent inhibitor of human renin (Ki with tetradecapeptide, 0.4 X 10(-9) M). It has a high enzyme specificity (Ki values against human pepsin, gastricsin, and cathepsin D are 5 X 10(-6), 3 X 10(-6), and 0.6 X 10(-6) M) and is also species specific (IC50 values against human, marmoset, dog, and rat plasma renins are 7 X 10(-10), 7 X 10(-10), 7 X 10(-9), and 1 X 10(-6) M). In vivo, CGP 38 560 inhibits plasma renin activity (PRA) and lowers blood pressure (BP) after oral administration to conscious, normotensive, furosemide-pretreated marmosets. A dose of 10 mg/kg induces complete inhibition of PRA and a decrease in BP of 23 +/- 3 mm Hg (n = 4) after 30 min. These effects persist for up to 2 h. Blockade of the renin-angiotensin system appears to cause the hypotensive response since it is completely prevented by pretreatment with a converting-enzyme inhibitor. These findings demonstrate that the molecular size of renin inhibitors may be reduced to improve their oral activity without loss of potency or specificity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2476594&dopt=Abstract
Acta Otolaryngol. 1982 Sep-Oct;94(3-4):307-16.
A survey of the effects of loop diuretics on the zonulae occludentes of the perilymph-endolymph barrier by freeze fracture.
Rarey KE, Ross MD.
The acute (30 min) effects of the loop diuretics piretanide, ethacrynic acid, bumetanide, furosemide, and azosemide, and the chronic (8 days) effects of furosemide and bumetanide on the zonulae occludentes (tight junctions) of the perilymph-endolymph barrier in the stria vascularis and in Reissner's membrane of the basal cochlear turns were studied by freeze-fracture. Quantitative analysis of their effects indicated that the structural integrity of the barrier was modified by either as increase or a decrease in the number, depth, and density of the strands of the tight junctions of the strial marginal cells. Only azosemide appeared to modify the tight junctions between the epithelial cells of Reissner's membrane, but it had little effect on the strial junctions. The tight junctions between the basal cells of the stria appeared to be the least affected by the various loop diuretics, although piretanide appeared to increase randomly the intercellular spaces lying between the strands.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7148443&dopt=Abstract
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