Diuretics in the therapy of hypertension.

Antihypertensive monopharmacotherapy with diuretics renders blood pressure (BP) values under control in a large percentage of patients suffering from essential hypertension, and it reduces cardiovascular morbidity and mortality. Diuretics are effective in adult and elderly hypertensive subjects, independently of their race. Treatments with classic (high) doses of antihypertensive diuretics, such as 25 mg hydrochlorothiazide once daily, raise the activity of the RAA system, decrease plasma potassium and magnesium concentrations, and cause untoward changes in carbohydrate metabolism and in the plasma lipid profile. These changes appear to limit the positive response of cardiovascular prognosis to antihypertensive therapy with classic doses of diuretics. Lower doses of diuretics reduce high BP to the sought extent in many patients, and they do not elicit or cause only mild unfavourable neuroendocrine and metabolic changes. When a low dose of an antihypertensive diuretic substance is used as monopharmacotherapy, it may take 12-14 weeks after the initiation of treatment for BP to attain final stable values. The following low-dose oral formulations of diuretics constitute effective once-daily monopharmacotherapies for mild-to-moderate uncomplicated essential hypertension: bendrofluazide 1.25 mg, chlorthalidone 12.5 and 15 mg, cicletanine 50 mg, cyclopenthiazide 0.125 mg, HCTZ 12.5 mg, and torasemide 2.5 and 5 mg. These formulations are safer than classically used high-dose formulations such as hydrochlorothiazide 25 and 50 mg.

Diuretics in the treatment of patients who present congestive heart failure and hypertension.

The main operational objective of diuretic therapy in patients who present congestive heart failure and hypertension is to reduce or to suppress excess bodily fluid. Effective diuretic therapy decreases cardiac size when the heart is dilated, and it reduces lung congestion and excess water. Consequently, external respiratory work diminishes and cardiac output would be redistributed in favour of systemic vascular beds other than that of the respiratory muscles; dyspnoea decreases markedly and there is a slight reduction in fatigue. This clinical improvement and the fall in body weight caused by diuretics entail an increase in effort capacity. Subsequent exercise training ameliorates the abnormal ventilatory response to physical effort and the skeletal muscle myopathy that occur in heart failure, and thereby it attenuates dyspnoea and decreases fatigue further. Loop and/or thiazide-type diuretics may be used to augment natriuresis in patients with congestive heart failure and hypertension. The state of renal function, the existence of certain co-morbid conditions, potential untoward drug actions, and possible interactions of diuretics with nutrients and with other drugs are some of the factors that must be considered at the time of deciding on the diuretic drug(s) and dose(s) to be prescribed. Spironolactone has been found to increase life expectancy and to reduce hospitalisation frequency when added to the conventional therapeutic regimen of patients with advanced congestive heart failure and systolic dysfunction. Therefore, spironolactone should be the drug of choice to oppose the kaliuretic effect of a loop or of a thiazide-type diuretic.

Estudio multicéntrico abierto no comparativo sobre la eficacia y la seguridad del acetónido de triamcinolona -inhalador nasal- una vez al día por tres meses en los síntomas de rinitis alérgica perenne / Non operative open label multicenter study on the efficacy and security of triamcinolone acetonide -nasal inhalator- once daily for three months in the treatment of the symptoms of permanent allergic rhinitis

Objetivo: evaluar la respuesta clínica (evolución de los síntomas de rinitis y manifestaciones alérgicas) en un grupo de pacientes con diagnóstico de rinitis alérgica perenne, luego de la administración de acetónido de triamcinolona -inhalador nasal- 110 a 220 mcg/1 vez al día (según la edad y severidad de los síntomas) y describir la tolerabilidad de la medicación administrada durante 3 meses. Diseño: estudio clínico observacional, descriptivo (serie de casos)., fase IV, no comparativo, abierto. Pacientes centros: fueron incluidos en el estudio 61 pacientes evaluados en 14 centros, con diagnóstico de rinitis alérgica perenne, mayores de 4 años, sin contraindicaciones para administración de acetónido de triamcinolona. Variables de seguridad y eficacia: frecuencia de eventos adversos. Evolución de una escala de severidad de la sintomatología de rinitis en 4 dominios: congestión nasal, estornudos, prurito y secreción nasal. Evaluación global subjetiva de mejoría por parte del médico tratante y del paciente. Resultados: se reclutaron 61 pacientes, 26 hombres (42,6 por ciento) y 35 mujeres (57,4 por ciento), con edades entre 4 y 48 años (promedio: 23 años). El seguimiento planeado a 3 meses fue logrado en 52 sujetos. Se administró una dosis diaria de acetónido de triamcinolona -inhalador nasal- por un período de 12 semanas. Los pacientes fueron evaluados antes de iniciar el tratamiento y a las semanas 6 y 12. Se produjo una reducción significativa en el puntaje de severidad de la rinitis de un valor mediano de 10 antes de tratamiento a 0 a las 12 semanas (p<0,001). No se presentaron efectos adversos severos y solo un efecto leve (costras nasales) fue relacionado con la administración de acetónido de triamcinolona -inhalador nasal- , no obstante no se requirió descontinuar el medicamento. Conclusiones: el tratamiento de los síntomas de la rinitis alérgica perenne con acetónido de triamcinolona -inhalador nasal- mostró una reducción clínica y estadísticamente significativa de la sintomatología en la mayoría de los pacientes tratados y fue excelentemente tolerado

Eficacia de la claritromicina [Klacina] en infecciones de la orofaringe / Efficacy of clariotromicine [Klacina] in oralpharynx infections

El presente estudio, prospectivo no controlado, evalúa la eficacia clínica de un preparado de claritromicina oral, Klacina© fabricado por Tecnoquímicas S.A. de Cali - Colombia, en el tratamiento de faringoamigdalitis aguda por estreptococo beta hemolítico del grupo A (EBHGA). Los pacientes se seleccionaron dentro de aquellos que consultaron por un cuadro clínico compatible con faringoamigdalitis estreptocóccica y que además tuvieran una prueba rápida de detección de EBHGA positiva. Se incluyeron inicialmente en el estudio 60 pacientes, en cada uno de los cuales se evaluó la sintomatología clínica al ingreso y el final del tratamiento, se tomó cultivo para EBHGA al inicio y final del mismo y se prescribió el nuevo preparado de claritromicina, Klacina© tabletas de 500 mg, 1 cada 12 horas por espacio de 10 días. Se descartaron 5 pacientes por diferentes causas y finalmente quedaron 55 pacientes para el análisis de los datos. El 100 por ciento (55 pacientes) tuvieron cultivo positivo al comienzo del tratamiento. En el 96,4 por ciento de los casos (53 pacientes) el cultivo y antibiograma revelaron EBHGA y el 3,6 por ciento (2 pacientes) estreptococo beta hemolítico del grupo B. Al concluir el estudio, 100 por ciento de los pacientes estaban curados clínicamente y en 98,2 por ciento (54 pacientes) los cultivos fueron negativos, solamente en el 1,8 por ciento (1 paciente) se encontró cultivo positivo para EBHGA. El 90,9 por ciento (50 pacientes) expresaron no tener molestias o efectos secundarios al finalizar el tratamiento, sólo el 9,1 por ciento (5 pacientes) manifestó algún efecto colateral, 3 pacientes alteraciones gustativas y 2 pacientes ardor epigástrico. En conclusión, Klacina©, claritromicina fabricada por Tecnoquímicas S.A. usada dos veces al día durante un periodo de 10 días ha mostrado una erradicación bacteriológica alta del EBHGA, similar o superior a la reportada en estudios previos con la sustancia y se recomienda como una alternativa de tratamiento en pacientes con faringoamigdalitis por EBHGA. Los excelentes resultados encontrados con esta marca en especial, corroboran que se trata de una preparación farmacéutica de óptima calidad, que es altamente efectiva cuando se utiliza clínicamente, y que por lo tanto es confiable y segura si el médico la selecciona como la marca a prescribir en un determinado paciente

Diuretics in cardiovascular therapy: the new clinicopharmacological bases that matter.

Diuretics in current use include early distal tubular (i.e., thiazide-type), loop (i.e., furosemide-type), and potassium-and-hydrogen-retaining substances. Available oral formulations of diuretics differ in terms of their renal excretory potency in man, as formally assessed through the effect of a single dose on 24-hour natriuresis in healthy subjects. The 2.5 mg formulation of the loop diuretic torasemide does not increase mean 24-hour natriuresis, and it is therefore considered a very-low-dose formulation. Amiloride 5 mg and torasemide 5 mg and 10 mg, which increase mean 24-hour natriuresis by less than 40%, are considered low-dose or low-potency diuretic formulations of diuretic substances. Hydrochlorothiazide 25 and 50 mg, furosemide 40 and 80 mg, and torasemide 20 mg, which increase mean 24-hour natriuresis by more than 40%, are considered high-dose or high-potency formulations. A rebound in natriuresis follows the early-after-dosing increase in this variables caused by loop diuretics; hence many oral formulations of loop substances are less potent natriuretics than most oral formulations of thiazide-type diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar natriuretic potencies. During once-daily administration of diuretic formulations of diuretics to subjects without edema and normal renal function, the increases in 24-hour natriuresis and diuresis that follow the first dose disappear or attenuate markedly. This is due to neuroendocrine reactions to diuretic-induced sodium loss and its attendant hemodynamic shifts. Some of these reactions, e.g. the increase in plasma aldosterone that takes place, account for an elevation in kaliuresis that occurs during once-daily treatment with a high-dose formulation of a thiazide-type diuretic. Common fixed-dose combinations of a thiazide-type or a loop diuretic and a potassium-and-hydrogen-retaining substance generally do not change kaliuresis, but they increase natriuresis strikingly. Thiazide-type and loop diuretics decrease and increase calciuresis respectively; none of these actions wanes during prolonged administration. Plasma renin activity and aldosterone do not rise in response to very-low-dose formulations of loop diuretics taken once daily. Glomerular filtration rate tends to fall in the course of once-daily administration of high-dose formulations of diuretics, but not during prolonged once-daily treatment with very-low-dose formulations of loop diuretics.

Angiotensin-converting enzyme inhibitors in the clinical setting of chronic congestive heart failure.

The addition of an angiotensin-converting enzyme (ACE) inhibitor to digitalis and diuretics in chronic congestive heart failure (CHF) prolongs survival and improves the clinical condition of patients. These actions depend on the inhibition of ACE and are, therefore, common to all ACE inhibitors. Thus, the inclusion of an ACE inhibitor in the therapeutic regimen of chronic CHF is mandatory, whenever feasible. The use of ACE inhibitors in chronic CHF should avoid symptomatic hypotension and inordinate decreases in renal function. To this end, ACE inhibitor therapy should progress by gradually increasing doses, and sodium intake and dosages of diuretics and ACE inhibitors should be adjusted in the light of changing circumstances. ACE inhibitors with short elimination half-lives should be preferred in chronic CHF, since they allow quicker dose adjustment than their longer-acting congeners, and given that compliance with once and twice daily dosing would be similar.

Loop diuretics versus others in the treatment of congestive heart failure after myocardial infarction.

Most frequently, diuretic therapy in congestive heart failure has as its main objective ridding the lungs of water. The work of the muscles of external respiration is thus decreased, the fraction of cardiac output that is distributed to vascular beds other than that of the respiratory muscles is consequently increased, and the functional and clinical condition of the patient improves. Diuretic therapy does not change cardiac output significantly in most cases; in some circumstances diuretic therapy may increase cardiac output in a clinically relevant fashion, and in some other cases diuretic therapy may lower cardiac output to the extent of impairing the overall functional situation. The dose of diuretics should be the minimal compatible with the prosecution of the main clinical objective (class betterment), to minimize possible increases in the afterload to the left ventricle (intravenous administration), to minimize hemodynamically detrimental decreases in the preload, and to minimize the likelihood of development or the severity of undesired changes in plasma biochemistry (hyponatremia, hypokalemia, hypomagnesemia, hyperuricemia, etc.). Loop diuretics are preferred shortly after myocardial infarction, given the ample dose-effect range of these substances and their relatively benign effect on renal blood flow. During chronic therapy, loop diuretics at low doses may be tried first, and the dose may be increased if necessary, provided higher doses do not cause symptomatic falls in cardiac output through the striking renal excretory response that these drugs elicit shortly after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal excretory responses to single and repeated administration of diuretics in healthy subjects: clinical connotations.

Administration of an initial oral dose of hydrochlorothiazide 25 mg to healthy subjects is followed by increased 24-hour urinary outputs of sodium, chloride, and potassium. On the fourth day of once-daily dosing with hydrochlorothiazide 25 mg, 24-hour natriuresis and chloriuresis are no longer augmented, but the elevation in 24-hour kaliuresis that follows the first dose remains unchanged. Twenty-four-hour urinary calcium output is consistently reduced during repeated once-daily administration of hydrochlorothiazide 25 mg. The first oral dose of the loop diuretic torasemide augments the average natriuresis and kaliuresis in the 6 hours immediately after dosing in healthy subjects, in a dose-dependent fashion, within the 2.5 to 10-mg range. These increased urinary outputs are followed by rebounds below postplacebo values between 6 and 24 hours after dosing. As a result of this biphasic response, torasemide 2.5 mg qualifies as a nondiuretic formulation (it does not elevate 24-hour natriuresis), whereas torasemide 5 and 10 mg qualify as diuretic formulations. After the seventh dose of torasemide 5 or 10 mg during a regimen of once-daily therapy, 24-hour urinary sodium and chloride outputs no longer differ from their postplacebo counterparts. Twenty-four-hour kaliuresis tends to increase in a dose-dependent fashion after the first dose of torasemide (torasemide 2.5 and 5 mg do not augment it significantly), but this tendency is no longer present after the seventh once-daily dose, when torasemide (2.5, 5, or 10 mg) does not elevate the mean 24-hour kaliuresis. Twenty-four-hour calciuresis tends to increase in a dose-dependent manner (torasemide 2.5 mg does not elevate it significantly) after the first dose of torasemide; this calciuretic effect does not change in intensity after 7 days of once-daily treatment. The time course of natriuresis over the 24 hours following the administration of any given formulation of a loop or of an early distal tubular diuretic to healthy subjects is alike after the first and after the nth once-daily dose; therefore, it constitutes a definite characteristic of any given oral formulation. In the case of torasemide, lower doses have more protracted effects on natriuresis, to the extent that the time course of natriuresis over the 24 hours after administration of torasemide 2.5 mg to healthy subjects resembles the time course after administration of hydrochlorothiazide 25 mg, rather than the time course after administration of the overtly diuretic formulation torasemide 10 mg.

Clinicopharmacological reappraisal of the potency of diuretics.

From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively on the basis of the changes in 24-hour natriuresis, with respect to 24-hour natriuresis after placebo, caused by single oral doses administered to healthy adult subjects who are in habitual and steady-state external sodium balance. The potency of various formulations of loop (e.g., furosemide), of early distal tubular (e.g., the thiazides), and of potassium-retaining diuretics, as well as of several combinations of diuretics, has been evaluated in a series of studies. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are definitely nondiuretic. The majority of the other formulations of loop diuretics studied are, in general, comparatively less potent than most of the common formulations of early distal tubular diuretics studied. As a general rule, most common formulations of early distal tubular diuretics are at least not less potent than the majority of common formulations of loop diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. Loop diuretics increase mean renal sodium output strikingly within the first few (0-6) hours after dosing, but this forced excretion is followed by a rebound with respect to postplacebo mean urinary sodium flow; the rebound usually takes place between 6 and 24 hours after dosing. However, no rebound in mean urinary sodium flow occurs during the 24 hours following a single dose of a distal tubular diuretic; these substances increase urinary sodium excretion with lower maximal intensity but more protractedly than loop diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal excretory profiles of loop diuretics: consequences for therapeutic application.

In healthy subjects, 24-h natriuresis, kaliuresis, calciuresis, and magnesiuresis increase in response to the first oral dose of a standard (diuretic) formulation of a loop diuretic, such as furosemide 40 mg. However, low-dose formulations of loop diuretics, such as torasemide 2.5 mg, do not elevate 24-h natriuresis after the first dose is administered to normal individuals who are in steady-state habitual sodium balance; these formulations of loop diuretics are consequently labeled as nondiuretic formulations (of diuretic substances). Nondiuretic formulations of loop diuretics do not increase the 24-h urinary outputs of sodium, potassium, calcium, or magnesium after the first dose or in the course of repeated once-daily administration to healthy subjects. The 24-h natriuretic response to the first dose of standard (diuretic) formulations of loop diuretics wanes during repeated once-daily administration to healthy individuals, whereas the kaliuretic response becomes slightly attenuated, and calciuresis and magnesiuresis bear little change. Once-daily treatment with any formulation of a loop diuretic may result in an increase in plasma urate concentration. Nondiuretic formulations of loop diuretics, which are efficacious as once-daily monopharmacotherapy for high blood pressure, should be tried before standard (diuretic) formulations of diuretics are used in the treatment of uncomplicated essential hypertension. When loop diuretics are employed in the treatment of congestive heart failure, the minimal dose compatible with the attainment of clinical objectives should be used.

Effects of diuretics on renal excretory function.

From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively, on the basis of placebo-controlled changes in 24 h natriuresis, following single oral doses administered to healthy adult subjects who are in steady-state habitual external sodium balance. The potency of 30 diuretic formulations has been evaluated. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are non-diuretic. The majority of the other formulations of loop diuretics studied (e.g. furosemide 40 mg and torasemide 5 and 10 mg) are comparatively less potent than most of the common formulations of early distal tubular diuretics studied (e.g. hydrochlorothiazide 25 and 50 mg, xipamide 10, 20 and 40 mg). Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. The presence of a rebound in natriuresis between 6 and 24 h after administration of loop diuretics make the majority of the common formulations of these drugs less potent than most common formulations of thiazide-type diuretics.

Effects of angiotensin-converting enzyme inhibitors on urinary excretions: interactions with diuretics.

The excretions of urinary sodium, potassium, magnesium, urate, and water after dosing with diuretics or the angiotensin-converting enzyme inhibitor perindopril are reported, as well as the results of other recent studies. Perindopril in low dose had no significant effect on any of these 24-hour urinary excretions and in high dose, in contrast to captopril and enalapril, does not increase magnesium loss. These effects were studied in healthy volunteers, which may not reflect urinary excretions in hypertensive patients.

Time course of the blood pressure response to oral isradipine in uncomplicated mild-to-moderate essential hypertension.

Forty-five patients with supine diastolic blood pressures (DBPs) above 95 mm Hg at the end of a four-week placebo run-in period were randomized to receive either 1.25 mg, 2.5 mg, or 5 mg isradipine twice daily as monotherapy for 12 weeks. Blood pressures (BP) were measured every 14 days, always by the same observer and using standard techniques. The Montevideo Mathematical Model was used to determine the time course of the response to treatment in each dosage group. Of the 33 patients who completed the study, four of the 12 patients receiving 1.25 mg isradipine twice daily had their BP controlled by weeks 10 or 12 (supine DBP less than or equal to 90 mm Hg), seven of 11 by 2.5 mg twice daily, and five of 10 by 5 mg twice daily. Mean DBPs for each dosage group were significantly reduced by week 12 (P less than .015 in all groups). The Montevideo Model allows estimation of the time after onset of treatment by which BP is reduced by a given amount. This model indicated that, with 2.5 mg isradipine twice daily, a fall in mean arterial pressure of 10 mm Hg is to be expected within three weeks of initiating drug administration.

Effects of diuretics on outputs and flows of urine and urinary solutes in healthy subjects.

The effects of single oral doses of common formulations of diuretics (i.e. formulations on the market or designed to be marketed) on 24-hour diuresis and natriuresis in healthy subjects are considered as a measure of the renal excretory potency of diuretics. Common formulations of distal tubular diuretics (e.g. hydrochlorothiazide 25mg, xipamide 10mg and 20mg) are more potent diuretics and natriuretics than common formulations of loop diuretics [e.g. furosemide (frusemide) 40mg, torasemide 2.5, 5 and 10mg]. Indeed, some common formulations of loop diuretics, such as torasemide 2.5, do not increase 24-hour diuresis or natriuresis in healthy subjects. 24-hour kaliuresis and magnesiuresis are elevated by common formulations of distal tubular diuretics, but they are only slightly increased or (more usually) not affected by common formulations of loop diuretics, when single doses are administered to healthy individuals. Common formulations of loop diuretics have lower diuretic and natriuretic potency and lower kaliuretic and magnesiuretic effects than common formulations of distal tubular diuretics, because the pronounced elevations in urinary excretions caused by loop diuretics during the first 6 hours after dosing are followed by rebounds, with respect to post-placebo excretions, between 6 and 24 hours after dosing. These rebounds, which affect the urinary flows of fluid, chloride, sodium, potassium and magnesium, do not occur after administration of common formulations of distal tubular diuretics, at least during the first 24 hours after administration of single doses to healthy subjects. The time courses of urinary excretions after loop diuretics are dose dependent. Higher doses produce more rapid changes in the urinary flows of fluid, chloride, sodium, potassium and magnesium than lower doses, to the extent that single administration of torasemide 2.5 or 5mg to healthy subjects is followed by urinary fluid and solute flows whose time courses resemble those after administration of hydrochlorothiazide 25mg.

Renal excretory actions of furosemide, of hydrochlorothiazide and of the vasodilator flosequinan in healthy subjects.

The responses of urine and urinary solute outputs and flows to single doses of 80 mg furosemide, 25 mg hydrochlorothiazide, and 100 or 200 mg flosequinan were investigated in healthy subjects using a double-blind, randomized, crossover design. Treatment days were separated by 7 days. Volumes of urine passed between 0 and 3, 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after drug administration were determined and urinary concentrations of chloride, sodium, potassium, calcium, magnesium, phosphate, zinc, urate, urea and creatinine were measured. Venous blood was taken before and 6 and 24 h after dosing and the serum was analysed for the same solutes as urine. Excretions of urine and urinary solutes accumulated at the end of each collection period after each formulation were fitted by the UY function, whose derivative provided corresponding flows as functions of time. Instantaneous renal clearances of solutes 6 and 24 h after dosing were evaluated from the flows. This approach showed that 80 mg furosemide and 25 mg hydrochlorothiazide were equipotent 24-h natriuretics. Rapid urinary responses which then rebounded compared with the control responses were produced by 80 mg furosemide, whereas changes after 25 mg hydrochlorothiazide were smooth. Neither 100 or 200 mg flosequinan showed any important effect on urinary excretion.

Formal comparison of the antihypertensive effects of torasemide and other diuretics by the Montevideo mathematical model.

A formal comparison is carried out of the antihypertensive effect of torasemide (1-isopropyl-3- ([4-(3-methylphenylamino)pyridine]-3-sulfonyl)urea) and various other diuretics used as monotherapy. The analyzed data are the results of various independent studies. The time (t) courses of the mean values of supine or sitting systolic (S) and diastolic (D) arterial blood pressure (P) during treatment are analyzed by fitting the "Montevideo mathematical model", described here, to the clinical (experimental) data. Clinically-important values of P and t evaluated from the fitted functions permit the formal comparisons. Decays in P were evaluated by the reductions in SP and DP occurred at 1.17 and 7.54 weeks of treatment, by the times at which the fitted functions showed diminutions of 10, 15 and 20 mmHg and of 10%, 15% and 20% with respect to pretreatment SP and DP mean values, and by the time at which DP attained a value of 90 mmHg. In studies in which the pretreatment mean value of DP ranged between 105.6 and 110.5 mmHg, standard-dose indapamide (2.5 to 5 mg/d), and low-dose torasemide (2.5 to 5 mg/d) elicited similar decays in SP and DP; the antihypertensive effects of etozoline (200 to 400 mg/d) and of hydrochlorothiazide (25 to 50 mg/d) were slower than those of torasemide and indapamide. Cyclothiazide (5 mg/d) and a coprescribed sodium-restricted diet reduced DP, from a pretreatment mean value of 114 mmHg, slower than torasemide and indapamide but quicker than etozoline and hydrochlorothiazide. Torasemide and indapamide should be consequently preferred for the chronic treatment of uncomplicated essential hypertension in terms of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative antihypertensive effects of ketanserin and a ketanserin-hydrochlorothiazide combination administered once daily.

The effects of monotherapy with once-daily ketanserin (40 mg) were compared to those of ketanserin (40 mg) plus hydrochlorothiazide (25 mg) once daily in 21 patients with mild essential hypertension. After a placebo run-in period of 4 weeks, medication was randomly allocated. The study was double-blind and the double-dummy technique was used. The measurements of blood pressure during the 3-month treatment period showed a tendency for progressive decreases of the variable. Supine and erect blood pressure mean values were significantly reduced, between pretreatment and the end of week 12, by 17 and 12 mm Hg with ketanserin therapy and by 19 and 16 mm Hg with combination treatment, respectively. A mathematical model used for studying the evolution of erect diastolic blood pressure over time revealed that the combination lowered blood pressure at a higher rate than did ketanserin alone in the first week of treatment, but that thereafter the velocity of change was higher for ketanserin alone. Both treatments had equally effective antihypertensive effects after 12 weeks, although differences existed in the time courses of blood pressure changes. More prolonged studies are required in order to distinguish further between the medications used.

Angiotensin I converting enzyme inhibitors and the renal excretion of urate.

Hyperuricaemia carries with it a high risk of tophi development affecting connective tissue in kidney, skin and joints, its overt clinical expression being gout. Diuretics, which are invariably prescribed in congestive heart failure and widely used for the treatment of essential hypertension, may cause hyperuricaemia and predispose to gout by inducing renal retention of urate. The angiotensin I converting enzyme inhibitors captopril and enalapril have been found to augment renal urate excretion both in normal volunteers and in hypertensive patients. Current evidence appears to indicate that the uricosuric effect of captopril and enalapril could be due to the rises in renin and angiotensin I these drugs elicit by angiotensin I converting enzyme inhibition, and/or to pharmacological actions not related, at least directly, to the renin-angiotensin-aldosterone system. Serum urate levels have been significantly reduced by monotherapy with captopril in hypertensive patients suffering from hyperuricaemia. Diuretic-induced hyperuricaemia in hypertensive patients can be prevented or counteracted by the administration of captopril and enalapril. Available clinical data support the argument that captopril and enalapril should be used as first choice drugs for the treatment of hyperuricaemic hypertensive patients. When diuretic-induced hyperuricaemia develops in patients suffering from congestive heart failure, captopril or enalapril should be added to the therapeutic regime in doses capable of countering the shift in plasma urate concentration, provided the clinical condition of the patients permits such additional pharmacological treatment. Therapy with captopril and enalapril should preferably be instituted in a gradual manner, especially in patients with hyperuricaemia, in order to prevent the precipitation of urate in the kidney and in the urinary tract.