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PubMed1982

Stimulation of renal sodium excretion in mature rats.

In adult rats a saline load is followed by an increase in renal excretion of sodium and by a low rate of ion exchange (hydrogen ions and potassium for sodium), caused by inhibited aldosterone secretion. Under analogous conditions a saline load provoked sodium retention and a distinct increase in renal excretion of hydrogen ions and potassium in young rats, which can be explained by a non-regulated, very intensive ion exchange. The repeated administration of NaCl solution alone and in combination with cyclopenthiazide produced an accelerated maturation of kidney function in 10- and 33-day-old rats measurable by an increase in sodium excretion and reduced ion exchange. In adult rats as well as immediately after birth (5-day-old rats) this effect cannot be provoked by the various pretreatments acting in mature rats.

Aging↗
PubMed1979

Stimulation of kidney function in rats of different ages injured by nephrotoxic agents.

Intensity and duration of nephrotoxic effects can be characterized by measurement of renal p-aminohippurate (PAH) excretion. Single administration of potassium dichromate or glycerol is followed by a marked decrease of renal PAH excretion in dependence on the time after the administration as well as on the dosage used. Both agents are without effect in young rats with an immature tubular transport system for organic anions. As observed previously in rats with intact kidney function, renal PAH excretion can also be stimulated in rats with potassium dichromate or glycerol induced kidney damage. Stimulation of renal PAH excretion is possible in injured rats by repeated administrations of PAH and cyclopenthiazide, respectively. Exactly, the duration of injury is shortened whereas the intensity of the nephrotoxic effect is not changed. However, this effect depends on the age of rats as well as on the nephrotoxic agent administered.

Aging↗
PubMed1978

Drug-associated primary acute pancreatitis.

Drug histories were taken from 100 patients in their first attack of acute pancreatitis, and each was matched with a control subject of the same sex who was admitted to hospital as an emergency with acute abdominal pain, whose serum-amylase was within the normal range, and whose age was within three years of the pancreatitis patient's. The major differences between the patient groups was in the use of cardiovascular agents, and this was primarily due to a statistically significant excess of diuretic takers among the pancreatitis patients. There was an associated excess of intake of digoxin and antihypertensive and anti-anginal agents, but neither difference was statistically significant. Other categories of drugs showed no substantial differences. The difference between the pancreatitic patients and controls is almost entirely accounted for by takers of cyclopenthiazide with potassium chloride and of frusemide, especially the former. Further clinical and experimental evidence is required before the role of diuretics and/or potassium chloride in causing acute pancreatitis can be determined.

Acute Disease↗
PubMed1981

Comparison of the beta-adrenoceptor blocking activity of oxprenolol, slow release oxprenolol and a combined oxprenolol diuretic preparation.

1 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg slow release oxprenolol with 0.25 mg cyclopenthiazide and placebo. Blood samples were obtained before and at 1, 2, 3, 6, 8, 12 and 24 h after drug administration and assayed for oxprenolol concentration. 2 The three formulations produced maximum reductions of 29% in the exercise tachycardia 3 to 6 h after drug administration. At 24 h the effects of the three preparations were not significantly different from placebo. 3 There were no significant differences in the plasma concentrations produced by the three formulations during the 24 h period. 4 These observations suggest that the slow release formulations of oxprenolol should be given twice daily to maintain cardiac beta-adrenoceptor blockade throughout a period of 24 h.

Adrenergic beta-Antagonists↗
PubMed1975

The effect of a low calorie diet or a thiazide diuretic on the incidence of pre-eclampsia and on birth weight.

A 1200 calorie diet or cyclopenthiazide with potassium was given to two groups of 51 high weight gain primigravidae and baby weight and the incidence of pre-eclampsia were compared with those in a matched control group. There was no difference in the development of pre-eclampsia, but the weight of babies in the control group was higher than in the treated groups. The body fat was reduced in the diet group and the total body water in the diuretic group.

Birth Weight↗
PubMed1979

A multicentre study examining the substitution of Trasidrex for the free combination of Slow-Trasicor and Navidrex-K.

A multicentre, open study of general practice patients with essential hypertension who were currently being treated with oxprenolol and cyclopenthiazide was undertaken in which the patients were transferred to Trasidrex for 12 weeks. Weight, blood pressure, heart rate and side-effects were assessed pre-trial and at 4-week intervals. A global assessment was also made at the same time intervals. The mean serum potassium remained virtually unchanged after 12 weeks treatment with Trasidrex. Blood pressure control was marginally improved during the study and it is thought possible that better patient compliance might explain this. Trasidrex was tolerated equally as well as the free combination.

Antihypertensive Agents↗
PubMed1980

An open comparison between free and a fixed combination of diuretic and beta-blocker in the management of essential hypertension.

A total of 1,117 patients with inadequately controlled hypertension in spite of treatment with a combination of diuretic and beta-adrenergic blocker were studied. Treatment was changed to one or two tablets daily of Trasidrex (160 mg oxprenolol hydrochloride in a sustained release formulation and 0.25 mg cyclopenthiazide) with a subsequent improvement, 4 weeks later, in blood pressure control. Side-effects of treatment were uncommon and treatment was approved by the majority of patients. The majority of doctors participating thought a fixed combination would improve patient compliance with therapy.

Adrenergic beta-Antagonists↗
PubMed1980

A patient compliance comparative study of three diuretics in the treatment of oedema.

Diurexan (xipamide) 40 mg daily was substituted for Navidrex-K (cyclopenthiazide 0.25 mg plus potassium 600 mg) or Moduretic (amiloride hydrochloride 5 mg plus hydrochlorthiazide 50 mg) in nineteen patients with oedema of cardiac origin. Comparative efficacy and patient acceptability were examined over a 4-week treatment period. In six patients their oedema was resolved and in a further seven their oedema was markedly reduced (six patients had no overt oedema pre-trial). The body-weight of nine patients decreased by an average of 1.4 kg whilst in seven patients it remained static and in three patients it increased by an average of 1.8 kg. Thirteen of the patients preferred Diurexan at the end of the 4-week trial period, four patients had no preference and two patients preferred their previous treatment.

Adult↗
PubMed1981

The treatment of hypertension in older patients: a double-blind, between-patient study, in previously treated patients comparing a diuretic, a beta-receptor antagonist, and their fixed combination.

Six hundred and forty-eight previously treated hypertensive patients, with a mean age of 64 years, were studied. In spite of treatment over a mean period of 18 months, their blood pressure was inadequately controlled, with an initial mean level of 180/108 mm Hg. Previous treatment which had consisted of either a diuretic alone, a beta-receptor antagonist alone or these two drugs in combination was discontinued and patients were randomly allocated, in double-blind manner, to a 6-week treatment course of cyclopenthiazide (Navidrex) or sustained release oxprenolol (Slow-Trasicor) or a fixed combination of these two compounds (Trasidrex) with the aim of lowering the diastolic pressure to less than 100 mm Hg. Blood pressure was substantially reduced in each treatment group, with the lowest final pressures in the group treated with the fixed combination, where 87% of the patients completing the study reached the target level of a diastolic pressure of less than 100 mm Hg. Very few side-effects of treatment were reported with any of these compounds. The results from this study suggest that these compounds in their standard dosage range are useful and safe antihypertensive agents in older patients. In those patients where blood pressure control with a single agent was proving difficult, the transfer to one or two tablets daily of the fixed combination (Trasidrex) produced a very satisfactory outcome in the large majority of cases.

Aged↗
PubMed1977

Prazosin combined with thiazide diuretic and beta-blocker in the treatment of hypertension.

In a study of 10 patients suffering from hypertension the results showed that combination treatment with prazosin, cyclopenthiazide and a beta-blocker produced a significant fall in blood pressure. Side-effects such as palpitations, headache, syncope and drowsiness which may occur with prazosin alone were obviated by combining prazosin with a beta-blocker.

Blood Pressure↗
PubMed1983

Comparative clinical trial of bemetizide/triamterene and cyclopenthiazide/potassium chloride combinations in patients with mild to moderate hypertension.

A double-blind trial was carried out to compare the combination of 25 mg bemetizide plus 50 mg triamterene ('Hypertane') and 0.25 mg cyclopenthiazide plus 600 mg potassium chloride ('Navidrex' K) in the treatment of mild to moderate essential hypertension. Two well matched groups of patients were treated for periods of 6 weeks with one or other of the drugs under test. There were 2-week placebo run-in and run-out periods. Blood pressure and laboratory investigations were performed every 2 weeks during the trial period. Both treatments resulted in similar overall statistically significant reductions in blood pressure during the trial. With bemetizide/triamterene, mean lying blood pressure decreased by 11.1/11.2 mmHg and mean standing blood pressure by 15.9/10.3 mmHg; with cyclopenthiazide/potassium chloride the corresponding reductions were 14.9/12.1 mmHg and 9.1/11.7 mmHg. The fact that some of the observed overall reduction seen with both drugs was due to 'placebo effect' is discussed but the clinical importance of overall changes is stressed. There were no significant differences between changes in blood pressure with the two treatments. Biochemical changes were those expected with thiazide diuretics. However, the decrease in potassium and increases in urea and uric acid levels were less with bemetizide/triamterene than with cyclopenthiazide/potassium chloride. Clinical tolerance of both treatments was good.

Adolescent↗
PubMed1975

Diuretics, beta blockers and vasodilators. Dosage in mild and moderate hypertension.

This paper presents experience with the treatment of mild to moderate hypertension by means of a thiazide diuretic (cyclopenthiazide), a small dose of a beta adrenergic blocking agent (oxprenolol) and progressively increasing doses of a vasodilator (hydrallazine). Satisfactory control of blood pressure was achieved in 38 of 41 cases without the production of distressing effects. This treatment regime was acceptable to patients and appears more promising than other currently available methods for blood pressure control.

Cyclopenthiazide↗
PubMed1975

[Stimulation of renal excretion of p-aminohippuric acid by repeated administration of drugs in young and adult rats].

The velocity of renal excretion of p-aminohippuric acid (PAH) could be raised by repeated administration of phenol red, probenecid and penicillin, which are actively transported by the acid carrier into the urine like PAH. These drugs produced an effect in fairly lower doses than PAH. The renal excretion of PAH can be accelerated by repeated pretreatment with the lipid-soluble drugs sulfaclomide, sulfamethoxypyridazine and cyclopenthiazide. It could be demonstrated that the stimulation of renal excretion of PAH by repeated administration of the investigated compounds is less pronounced in young rats than in adult animals.

Aminohippuric Acids↗
PubMed1979

Hydrallazine with beta-blocker and diuretic in the treatment of hypertension. A double-blind crossover study.

Thirty-seven hypertensive patients were treated with cyclopenthiazide, oxprenolol and hydrallazine. Blood pressure was controlled in 31 patients and a subsequent double-blind crossover study in 27 patients comparing hydrallazine with placebo confirmed the efficacy of hydrallazine in combination with diuretic and beta-adrenergic-blocking agent. The combination was effective in patients with renal hypertension and renal impairment. No adverse effects on renal function were observed. Patients who were slow acetylators had significantly better blood pressure control and more side effects. In view of the frequency of hydrallazine related side effects, prior institution of beta-adrenergic blocking drugs is desirable.

Adult↗
PubMed1987

Influence of diuretics on renal lithium excretion and tissue distribution of some cations in saline loaded young and adult rats.

In 5- and 105-day-old rats the effect of acetazolamide, cyclopenthiazide, and/or a saline load on renal lithium excretion as well as on lithium, sodium and potassium concentrations in serum and in various tissues (kidney, muscle, intestine, liver, brain) was investigated during the first 3 h after ip. administration of lithium. The administration of acetazolamide or saline led to a significant increase in renal lithium elimination in animals of both age groups, which could be stimulated additionally, when both substances were given simultaneously. In principle, increased renal lithium excretion is paralleled by enhanced sodium elimination. There was evidence for an inhibition of renal tubular lithium reabsorption and besides, extrarenal changes were observed in the lithium, sodium, and potassium distribution, which have consequences for lithium elimination as well. Lithium is accumulated to a different extent in each of the tissues investigated. Furthermore, tissue accumulation and efflux rate of lithium strongly depend on age. The influences of the diuretics and/or saline administration on possible mechanisms of renal and extrarenal lithium movements are discussed.

Acetazolamide↗
PubMed1981

Renal blood flow after stimulation of p-aminohippurate transport.

Repeated administration of cyclopenthiazide enhances renal PAH excretion in rats. In the 1st hr after an acute PAH load the renal excretion of PAH is doubled compared with controls. Haemodynamic measurements show that this acute PAH load is related to an increase in renal blood flow, in particular to a distinct increase in blood flow in the renal cortex. This increase in renal blood flow and in intrarenal blood distribution is higher than in stimulated rats. The increase in renal excretion of PAH is stimulated rats is not connected with an increase in renal blood flow. After an acute PAH load an additional increase in renal blood flow in stimulated rats could not be observed as compared with non stimulated control rats.

Aminohippuric Acids↗
PubMed1977

[Concentration of p-aminohippuric acid in the serum and kidney tissue during stimulation of renal excretion of foreign materials].

The renal excretion of p-aminohippuric acid (PAH) can be stimulated in adult rats by repeated applications of probenecid, cyclopenthiazide, and phenobarbital. The present studies have shown that this pretreatment significantly shortens the half-life for PAH too. In pretreated animals the PAH concentration decreases in the renal tissue more rapidly than in the control animals. These results were obtained in adult animals only but not in 5-day-old rats, in which the pretreatment had no effect upon the rate of renal PAH excretion. The pretreatment did not change the renal weight of 5-and 55-day-old rats.

Aminohippuric Acids↗