Drugs online research references
Arch Mal Coeur Vaiss. 1984 Oct;77(11):1220-5.
[Comparison of the cardiac, renal and endocrine effects of converting enzyme inhibition with those of a classical triple therapy in experimental renal hypertension]
[Article in French]
Dussaule JC, Michel JB, Auzan C, Alhenc-Gelas F, Corvol P, Menard J.
In the rat model of hypertension induced by a clip on the right renal artery, sparing the left kidney, we compared the efficacity and the endocrine, renal and cardiac effects of classical therapy (CT) of hypertension (Clonidine 0.2 mg/kg and Dihydralazine 15 mg/kg in 2 daily subcutaneous injections and Furosemide 30 mg/kg/day in the drinking water), with inhibition of the angiotensin converting enzyme with a new drug, the S-9490-3 (0.5 mg/kg in one daily administration). The untreated animals (HT: n = 12) had an average systolic blood pressure (SBP) of 215 +/- 32 mmHg. After 1 month' treatment, S-9490-3 (n = 13) lowers SBP to 144 +/- 32 mmHg compared to CT (n = 12) which lowered SBP to only 172 +/- 18 mmHg. The average plasma renin concentrations of the HT animals was four times the normal value (39 +/- 33 ng/ml/h) and both treatment regimes increased it further (S-9490-3: 129 +/- 65 ng/ml/h; CT: 97 +/- 73 ng/ml/h). Angiotensin levels fell in proportion to the increase in renin concentration. Plasma aldosterone was normalised by S-9490-3 (460 +/- 320 pg/ml) but remained as high after CT (850 +/- 650 pg/ml) as in the untreated HT animals (830 +/- 260 pg/ml). Despite the Furosemide, plasma volume increased significantly in the CT group.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6098234&dopt=Abstract
Fed Proc. 1983 Apr;42(6):1711-3.
Determinants of the overall response to furosemide: pharmacokinetics and pharmacodynamics.
Brater DC.
After an oral or i.v. dose of furosemide, there is considerable interindividual variability in the amount of unchanged drug delivered into the urine. On the average, approximately half as much reaches the intraluminal site of action with an oral compared with an i.v. dose. However, the natriuretic response to the same dose administered by either route is virtually the same. Similarly, after pretreatment with probenecid, the same total amount of furosemide in urine causes a greater overall response. It has been presumed that this paradox is accounted for by differences in rate of delivery of furosemide to the active site such that after an oral dose or after pretreatment with probenecid, amounts of drug are at the "steep" portion of the dose-response curve for longer periods of time. Our analysis shows that this is not the case. For furosemide, the amount of diuretic delivered into the urine that is maximally efficient (21.5 micrograms/min) is considerably less than the amount causing half-maximal response (69.8 micrograms/min). Oral administration or pretreatment with probenecid maintains drug close to this maximally efficient amount more persistently than does i.v. administration. By so doing, total response to an oral dose approaches that of i.v. dosing despite delivering half the amount of drug to the active site, and after probenecid an i.v. dose causes a greater response than i.v. dosing alone despite delivering the same amount of drug to the active site. These data emphasize the importance of the time course of delivery of drug to the active site as an independent determinant of overall response.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6832391&dopt=Abstract
Am J Physiol. 1983 Jun;244(6):F696-705.
Effect of osmotic shocks on rabbit kidney cortex slices.
Gilles R, Duchene C, Lambert I.
Rabbit kidney cortex slices behave an osmometers when withstanding hyperosmotic or hyposmotic shocks of amplitude up to pi 1/pi 2 = 1.25. For hyposmotic shocks of amplitude larger than or equal to pi 1/pi 2 = 1.50, the maximum swelling achieved is less than what can be expected on the basis of the van't Hoff relation, thereby indicating that a volume regulation process is taking place. Volume regulation in kidney slices can be dissociated into two distinct phases. The first one, of swelling limitation, is very rapid and keeps maximum cell volume at values lower than expected when the tissue is considered as an osmometer. This phase is followed by a slow volume readjustment process during which volume progressively decreases towards control values. The major intracellular osmotic effector loss during both swelling limitation and volume readjustment is Na+. The overall volume regulation process is insensitive to furosemide, vanadate, and bumetanide. Swelling limitation is blocked by addition of ouabain. Contrary to what has been believed previously, there is, however, no need to implicate control of the activity of a ouabain-sensitive, Na+/K+ pump in the Na-dependent volume regulation mechanism.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6859261&dopt=Abstract
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