Disease relevance of Arelix

• The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium-sparing properties [1].
• Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia [1].
• BUN increased in nine piretanide-treated patients; two were discontinued from the study because of progressive azotemia [1].
• Thus, piretanide appears to offer an effective alternative to other 'loop' diuretics for the treatment of oedematous diseases and to hydrochlorothiazide for the management of mild to moderate hypertension [2].
• When used to treat oedema caused by liver disease, piretanide 12 to 24 mg/day was successful in only about 50% of patients, but spironolactone added to the treatment regimen greatly increased the response rate [2].

High impact information on Arelix

• However, the addition of spironolactone, 150 mg/day, to piretanide was followed in these patients by a marked increase in diuresis and natriuresis [3].
• 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) [3].
• The addition of digoxin for 2 wk after piretanide alone for 2 wk did not decrease serum potassium and TBK, but RCP fell under the influence of piretanide with digoxin [4].
• Bumetanide, furosemide, and piretanide have similar pharmacokinetics, whereas the clearance of torasemide is less and the half-life concomitantly longer than the other 3 agents [5].
• 5. Comparison of data from the vas and taenia showed that 36Cl efflux into Cl(-)-free, HCO3(-)-free solution was about twice as fast in the taenia, and that bumetanide or piretanide reduced this efflux to about the same rate as that observed in the vas with or without the loop diuretic [6].

Chemical compound and disease context of Arelix

• In medium term trials in patients with congestive heart failure piretanide 6 mg/day produced equivalent symptomatic improvement as frusemide 40 mg/day [2].
• To test the dose responses of piretanide, ramipril, and their combination in patients with essential hypertension, a prospective, randomized, double-blind, placebo-controlled trial was conducted in 480 patients [7].
• 4 Piretanide (48 mg) appeared to be effective in advanced renal insufficiency, producing a significant increase in urine flow rate, in sodium, chloride, potassium and calcium excretion and in Cosm [8].
• New diuretics introduced into clinical medicine during the past decade include potent new loop diuretics such as bumetanide and piretanide, the uricosuric indanyloxyacetic acid derivative indacrinone, and a new generation of sulfamoyl diuretics such as indapamide and xipamide, which are recommended primarily for the treatment of hypertension [9].
• Efficacy of penbutolol + piretanide combinations in the treatment of arterial hypertension [10].

Biological context of Arelix

• The effect of the loop diuretic, piretanide (12 mg/day on blood pressure and intracellular electrolyte composition in red blood cells during a six-week treatment period was studied in 14 previously untreated essential hypertensive patients [11].
• Acute and chronic effects of the loop diuretic, piretanide, on baroreflex set point and sensitivity in hypertensive man [12].
• In in vitro experiments piretanide leads to effective inhibition of ADP-induced platelet aggregation with complete inhibition at 5 mM concentration [13].
• Pretreatment with probenecid produced significant increases in absolute peak and plasma diuretic concentrations, t1/2 and mean residence time while decreasing steady-state volume of distribution, total clearance, renal clearance and fraction of unchanged drug excreted without affecting the bioavailability of piretanide [14].
• The present results indicate that tubular secretion of piretanide is important for the diuretic response and that piretanide inhibits the fluid absorption in the loop of Henle and the tubuloglomerular feedback control which would otherwise blunt the diuretic response with a reduction in glomerular filtration rate [15].

Anatomical context of Arelix

• Piretanide is a potent 'loop' diuretic whose principal site of action is in the thick ascending limb of the loop of Henle [2].
• The demonstrated anionic selectivity, dependence on extracellular Na+ and susceptibility to blockade by the diuretic piretanide would strongly suggest that a coupled Na+-K+-Cl- co-transport system operates in submandibular glands as it does in other transporting epithelia to achieve K+ uptake [16].
• In cells which have normally directed gradients of Na+ and K+, chronic incubation in piretanide (10(-4) M) for up to 24 hr has no significant effect on the internal ion contents of HeLa (human carcinoma), MDCK (dog kidney epithelium) or BC3H1 (mouse smooth muscle) cell lines [17].
• Piretanide abolished the dorsal root potential elicited by ventral root stimulation [18].
• Characterization of a high affinity piretanide receptor on kidney membranes [19].

Associations of Arelix with other chemical compounds

• During a continuous infusion of inulin and cefazolin (10 mg/kg per h), six healthy male volunteers received a single intravenous injection of furosemide (0.3 mg/kg) or piretanide (0.1 mg/kg) or again an oral water load of 15 ml/kg over a 20-min period [20].
• Renal responses and pharmacokinetics of piretanide in humans: effect of route of administration, state of hydration and probenecid pretreatment [14].
• A surface analysis suggested that piretanide primarily reduced systolic blood pressure, whereas ramipril was more effective in reducing diastolic blood pressure [7].
• The effects of piretanide, a drug which blocks active chloride transport in other systems, was examined on amino acid responses and synaptic potentials in the frog spinal cord [18].
• Furosemide, piretanide and ozolinone induced a concentration-dependent decrease in renal tone (EC50 = 0.47 x 10(-4) mol/l, 1.03 x 10(-4) mol/l and 2.07 x 10(-4) mol/l respectively) in Wistar rats [21].

Gene context of Arelix

• The inhibitory action of SRIF on basal SCC was suppressed by piretanide and diphenylamine-2-carboxylate, compatible with the assumption that the Na+K+2Cl- co-transporter and Cl- channels, respectively, may be involved in this antisecretory action of SRIF [22].
• RESULTS: Independent of the basal TPMT activity, lowest IC50 values were calculated for furosemide (15-19 microM), followed by testosterone (30-72 microM), piretanide (300-313 microM) and AZA (430-532 microM) [23].
• TBK and RCP were measured before treatment to establish baseline values, after which all subjects received 6 mg piretanide a day for 14 days [4].
• 4. Responses to both peptides were inhibited by the presence of transport inhibitors, particularly diphenylamine-2-carboxylate (DPC, a chloride channel blocker) and piretanide (Na+-K+-2Cl- co-transport inhibitor) [24].
• 4. In both cell lines r alpha-CGRP-elevated short-circuit current was inhibited by the loop diuretic piretanide (200 microM) and by somatostatin (100 nM) [25].

Analytical, diagnostic and therapeutic context of Arelix

• Generally, piretanide has been well-tolerated in clinical trials, although the conventional tablet formulation has caused a relatively high incidence of acute adverse effects--these were greatly reduced with the introduction of the sustained release formulation [2].
• Thus, this property of these diuretics might be one of the factors contributing to the observation of increased Na reabsorption along the distal tubule after in vivo administration of furosemide and piretanide as reported in some micropuncture studies [26].
• Serum concentrations of piretanide were estimated by radioimmunoassay [27].
• 1 This study has compared the diuresis produced by a single oral administration of 6 mg piretanide, 9 mg piretanide and 1 mg bumetanide in a group of nine patients with cardiac failure using a balanced randomized design [28].
• Quantitative evaluation of ototoxic side effects of furosemide, piretanide, bumetanide, azosemide and ozolinone in the cat--a new approach to the problem of ototoxicity [29].

References