Xipamid, a potent new diuretic

Piyasena, K. H. G.; Havard, C. W. H.; Weber, J. C. P.

doi:10.1185/03007997509113658

Cited by 20 publications

(6 citation statements)

References 4 publications

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“…Xipamide is a potent non-thiazide diuretic with an action on the distal tubule (Gold & Viljoen, 1979;Leuschner, 1975) and possibly also the ascending loop of Henle (Leuschner, 1975). It is claimed to be equipotent with frusemide in its diuretic effect (Fischer & Lenhartz, 1970;Piyasena et al, 1975) and the drug has been used successfully in the treatment of drug-resistant oedema (Fischer & Lenhartz, 1970;Piyasena et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

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Xipamide and cyclopenthiazide in essential hypertension–comparative effects on blood pressure and plasma potassium.

Macgregor¹,

Banks²,

Markandu³

et al. 1982

Brit J Clinical Pharma

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1 The blood pressure lowering effect of xipamide, a non‐thiazide diuretic given for 6 weeks was compared in a randomised cross‐over trial with that of cyclopenthiazide in 14 patients with essential hypertension. 2 Xipamide 10 or 20 mg given once daily was as effective in lowering supine blood pressure as daily cyclopenthiazide 0.5 mg. There was no difference in the blood pressure lowering effect of 10 mg xipamide daily for 2 weeks compared to 20 mg daily given for a further 4 weeks. 3 Plasma potassium was reduced by both drugs, but markedly more after both 10 mg and 20 mg xipamide than after cyclopenthiazide 0.5 mg. By the sixth week of treatment 13 of 14 patients on xipamide but only 6 of 14 on cyclopenthiazide has plasma potassium concentrations of, or less than, 3.5 mmol/l. The fall in plasma potassium was significantly greater and the final plasma potassium concentration was significantly lower after either dose of xipamide than after cyclopenthiazide. 4 These results suggest that 10 mg or 20 mg of xipamide daily is effective in lowering blood pressure in hypertensive patients but is associated with hypokalaemia. In view of recent evidence linking diuretic‐induced hypokalaemia with cardiac dysrhythmias in patients with essential hypertension we would suggest that thiazide diuretics be used in preference to xipamide for the routine management of essential hypertension. Our results also suggest that the currently recommended dose of xipamide (20 mg) for the treatment of hypertension is excessive, and lower amounts than 10 mg per day might possibly be as effective in lowering blood pressure with less adverse metabolic consequences.

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Section: Introductionmentioning

confidence: 99%

“…The long duration of action of the drug (Fischer & Lenhartz, 1970;Piyasena et al, 1975), however, resembles that of the thiazides rather than the loop diuretics. Xipamide might, therefore, be useful in the management of hypertension.…”

Section: Introductionmentioning

confidence: 99%

Xipamide and cyclopenthiazide in essential hypertension–comparative effects on blood pressure and plasma potassium.

Macgregor¹,

Banks²,

Markandu³

et al. 1982

Brit J Clinical Pharma

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“…Xipamid (4-chloro-5-sulphamylsalicylic acid 2',6'-dimethylanilide) a non-thiazide diuretic is new to the United Kingdom, though several controlled clinical trials have been carried out in this country (Harding, Kalos, Weber & Dixon, 1974;Davies & Prichard, 1975;Piyasena, Havard & Weber, 1975). Its structure and pharmacology have been described by Harding et al (1974) and by Davies & Prichard (1975) and its diuretic activity appears to be roughly equivalent to that of frusemide (Piyasena et al, 1975). Its onset is, however slower and its effect more gradual, lasting for 12 h or more.…”

Section: Introductionmentioning

confidence: 99%

Once daily treatment of mild to moderate hypertension with xipamid: a controlled study.

Weber¹,

Bird²,

Cosh³

et al. 1977

Brit J Clinical Pharma

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A double-blind, placebo controlled, crossover trial of 20 and 40 mg of xipamid once daily in the treatment of mild to moderate hypertension is reported and some of the difficulties and pitfalls of multicentre trials of this type are described. 2 Both doses were significantly more effective in reducing the blood pressure than the placebo and neither was superior to the other. Both produced some potassium loss. Xipamid acted for at least 22 h and was effective in up to 83% of the patients. 3 Further trials are suggested to investigate the activity of a lower dose than 20 mg.

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“…This difference in blocker affinity is accentuated when CFTR is studied in polarized epithelia (Reddy and Quinton, 1999;present study), arguing that CFTR inhibition is an unlikely consequence of diuretic therapy. Loop diuretics inhibit NKCCs in the rank order: bumetanide > piretanide > furosemide = xipamide with block by bumetanide substantially stronger than that of furosemide (Piyasena et al, 1975;Schlatter et al, 1983;Hannaert et al, 2002). By contrast, loop diuretics inhibit CFTR with little difference in potency (rank order: xipamide ≥ bumetanide = piretanide ≥ furosemide) (present study).…”

Section: Differences Between Nkccs and Cftrmentioning

confidence: 99%

Loop diuretics are open‐channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics

Scott-Ward

Liu

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSELoop diuretics are widely used to inhibit the Na− co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl − channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade. EXPERIMENTAL APPROACHUsing the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR. KEY RESULTS When added to the intracellular solution, loop diuretics inhibited CFTR Cl− currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl − channels with 'very fast' speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with 'intermediate' speed and drug-induced blocking events were distinct from channel closures. CONCLUSIONS AND IMPLICATIONSStructure-activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.

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Xipamid, a potent new diuretic

Cited by 20 publications

References 4 publications

Xipamide and cyclopenthiazide in essential hypertension–comparative effects on blood pressure and plasma potassium.

Xipamide and cyclopenthiazide in essential hypertension–comparative effects on blood pressure and plasma potassium.

Once daily treatment of mild to moderate hypertension with xipamid: a controlled study.

Loop diuretics are open‐channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics

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