enalapril and Hypokalemia

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Adult; Blood Pressure; Calcium Channel Blockers; Captopril; Combined Modality Therapy; Coronary Disease; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypokalemia; Male; Methods; Middle Aged; Reserpine; Risk

To investigate whether enalapril (E) 10 mg and spironolactone (S) 100 mg attenuate the hypokalemic effect of inhaled terbutaline (T).. Randomized single-blind crossover. Subjects received the following treatment combinations: (a) placebo (P), (b) T alone, (c) T + E, or (d) T + S.. University Department of Clinical Pharmacology.. Twenty healthy volunteers (ten male, ten female) of mean age 22.8 +/- 3.1 years.. Serum potassium, magnesium, ECG changes (R-R interval, T wave, and QTc interval) for 4 h after terbutaline inhalation.. Baseline serum potassium levels were higher following prior treatment with E and S; P, 3.78 mmol/L (3.67 to 3.88); T + E, 3.93 mmol-1 (3.82 to 4.03); and T + S, 4.03 mmol/L (3.93 to 4.14) (p less than 0.05). Mean potassium concentrations over 4 h were also higher following prior treatment with E and S; T, 3.58 mmol/L (3.54 to 3.63); T + E, 3.68 mmol/L (3.64 to 3.72) (p less than 0.05); and T + S, 3.73 mmol/L (3.68 to 3.78) (p less than 0.01).. Enalapril and spironolactone protect against the fall in serum potassium over 4 h by elevating baseline potassium concentration. These potassium-sparing drugs, however, should not be used to prevent the hypokalemic and electrocardiographic sequelae of inhaled beta 2-agonists.

Topics: Adult; Electrocardiography; Enalapril; Female; Hemodynamics; Humans; Hypokalemia; Magnesium; Male; Potassium; Renin; Single-Blind Method; Spironolactone; Terbutaline

Two combinations of lisinopril and hydrochlorothiazide (L/HCTZ, 20 mg/12.5 mg and 20 mg/25 mg) are currently marketed. The licences are based primarily on a dose ratio study and a parallel titration study. In the former randomized study of 209 patients with sitting DBP of 90-115 mm Hg, the antihypertensive effects of L/HCTZ 20 mg/12.5 mg and 20 mg/25 mg were significantly greater than either lisinopril or hydrochlorothiazide monotherapy (P less than or equal to 0.01), while the effect of L/HCTZ 20 mg/6.25 mg, was greater than hydrochlorothiazide but not lisinopril monotherapy. In the latter study, 394 patients with sitting DBP of 90-120 mm Hg received lisinopril 20 mg, HCTZ 12.5 mg, or L/HCTZ 20 mg/12.5 mg once daily for 12 weeks of double-blind therapy. All of the dose regimens could be doubled at 4 and 8 weeks for adequate BP control. The L/HCTZ group had significantly greater effect than either monotherapy (P less than or equal to 0.01). Thus, concomitant therapy with lisinopril and hydrochlorothiazide provides BP reduction beyond that of either monocomponent. Studies on new combinations of lisinopril and hydrochlorothiazide are under way to increase prescribing options for practitioners.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Double-Blind Method; Drug Combinations; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Hypokalemia; Lisinopril

In a double blind study, 104 hypertensive patients were randomly allocated to two different stepped care programs for 6 months. Following a placebo run-in-phase, patients were given either Enalapril (EN) 20 mg once-a-day, or a Placebo (PL). Drugs were added as follow in a parallel stepwise sequence, until the goal blood pressure was obtained. First Hydrochlorothiazide (HCTZ) and then, if necessary, Oxprenolol (OXP) and Dihydralazine (DIH). The two goals of this study were to lower diastolic blood pressure below 90 mmHg and to maintain plasma potassium above 3.5 mmol/l. Amiloride was prescribed if plasma potassium was lower than 3.5 mmol/l. At the end of the study the EN group's blood pressure was 130 +/- 12/83 +/- 6 mmHg, the tablet's daily number was 2.6 +/- 1.8 and Amiloride was necessary in 15 patients. These parameters were significantly different from those observed in the Pl group (BP: 136 +/- 9/87 +/- 5 mmHg, tablets 4.2 +/- 2.4; amiloride necessary in 34 patients). The effects of HCTZ were evaluated in 32 patients previously treated by EN compared to 39 patients receiving PL. The converting enzyme inhibition minimized the fall in plasma potassium induced by HCTZ (3.6 t +/- 0.4 vs 3.3 +/- 0.5 mmol/l, p less than 0.05). Related to the HCTZ dose (mg/kg), the plasma potassium fall is lower in the EN group (0.46 +/- 1.1) than in the PL group (0.94 +/- 0.9, p less than 0.05). The plasma potassium reduction could not be predicted by age, plasma renin activity, plasma and urinary aldosterone or urinary kallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Clinical Trials as Topic; Enalapril; Humans; Hydrochlorothiazide; Hypertension; Hypokalemia; Random Allocation

The study reported here prospectively evaluated the prevention of diuretic-induced secondary hyperaldosteronism and hypokalemia by a converting enzyme inhibitor, enalapril (MK 421). Eighteen normal subjects were randomized into three groups: (1) a HCTZ group (hydrochlorothiazide (HCTZ) 50 mg/day); (2) a MK-421 group (MK-421 10 mg/day); and (3) a HCTZ + MK-421 group [HCTZ 50 mg/day plus MK-421 10 mg/day]. Following a five-day control and a 28-day treatment period, the HCTZ group demonstrated an attenuated but persistent secondary hyperaldosteronism and hypokalemia, the MK-421 group manifested a gradual decline in aldosterone secretion, and the HCTZ + MK-421 group had a delayed but effective correction of secondary hyperaldosteronism and hypokalemia at 28 days but not before. In conclusion, MK-421 reversed diuretic-induced secondary hyperaldosteronism and hypokalemia after 28 days of hydrochlorothiazide therapy. Therefore, converting enzyme inhibitors, such as enalapril, provide useful adjunctive therapy in diuretic-treated patients, but potassium supplementation may be required before the start of four weeks of combined therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Diuretics; Electrolytes; Enalapril; Humans; Hydrochlorothiazide; Hyperaldosteronism; Hypokalemia; Random Allocation; Renin

This presentation is a summary of our recent clinical studies on the therapeutic use of a new potassium-sparing diuretic, amiloride, and a converting enzyme inhibitor, MK-421, in preventing hypokalemia associated with primary and secondary hyperaldosteronism. These drugs are quite different in their physiologic action but they both may be effective in preventing the potassium depletion associated with increased aldosterone production. Amiloride, which blocks the sodium channels in distal renal tubular cells, was administered to 10 patients with primary hyperaldosteronism and five patients with Bartter's syndrome (secondary hyperaldosteronism). Amiloride, at doses of 10-40 mg/day, increased mean plasma potassium levels in both primary hyperaldosteronism (3.2-4.5 mEq/L) and, to a lesser extent, in Bartter's syndrome (2.5-3.6 mEq/L). The blood pressure fell slightly but significantly in primary hyperaldosteronism (171/112 vs 150/97 mm Hg) and remained unchanged in Bartter's syndrome (116/80 vs 117/71 mm Hg). The plasma renin activity and plasma aldosterone rose in primary aldosteronism (PRA 0.39-2.21 ng A1/m1/h and PA 28.4-54.3 ng/d1); but in Bartter's syndrome, the PRA declined (25.3-11.9 ng A1/m1/h) and the PA rose (19.5-38.0 ng/d1). The discrepancy in the PRA between primary aldosteronism and Bartter's syndrome may be due to the effects of potassium repletion on suppressing renin and stimulating aldosterone; while in primary aldosteronism, a mild diuretic effect could explain the rise in PRA. In both of these disorders, despite the rise in plasma potassium levels, amiloride produced a counter-therapeutic rise in PA which could potentiate further potassium losses. Therefore, we undertook a study to evaluate the prevention of diuretic-induced hypokalemia and secondary hyperaldosteronism using a new converting enzyme inhibitor, MK-421. Eighteen normal subjects were randomized into three groups receiving either (1) hydrochlorothiazide alone (50 mg/day), (2) MK-421 alone (10 mg/day), or (3) hydrochlorothiazide (50 mg/day) plus MK-421 (10 mg/day). Although MK-421 did not prevent diuretic-induced hypokalemia or hyperaldosteronism in the first week, after that time hypokalemia was reversed and ASR returned to normal. In these studies, it therefore appears that while potassium-sparing diuretics may remain the medical mainstay in treating primary aldosteronism, new converting enzyme inhibitors such as MK-421 may be more effective in treating secondary hyperaldoster

Topics: Adult; Aged; Aldosterone; Amiloride; Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Diuretics; Electrolytes; Enalapril; Female; Humans; Hydrochlorothiazide; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Pyrazines; Renin

We report a 72 years old hypertensive female, treated with enalapril 10 mg/day and hydrochlorothiazide 25 mg/day during three years. She presented a depressive disorder and cytalopram was prescribed in a dose of 10 mg/day. Two weeks before admission, a serum electrolyte analysis disclosed normal results and the cytalopram dose was increased to 20 mg/day. The patient was admitted with a hyponatremic encephalopathy with a plasma sodium of 100 mEq/L and a plasma potassium of 2.0 mEq/L. Cytalopram, enalapril and hydrochlorothiazide were discontinued, hypertonic NaCl and KCl were administered. The patient had a favorable evolution with a remarkable improvement of her symptoms.

Topics: Aged; Antidepressive Agents, Second-Generation; Antihypertensive Agents; Citalopram; Enalapril; Female; Humans; Hydrochlorothiazide; Hypokalemia; Hyponatremia; Severity of Illness Index; Time Factors

Angiotensin II stimulates the proximal tubular Na/H antiporter and increases proximal tubular cell pH. Because intracellular pH may affect urinary citrate excretion and enzymes responsible for renal citrate metabolism, the present studies examined the effect of enalapril, an angiotensin converting enzyme inhibitor, on the activity of renal cortical ATP citrate lyase and urinary citrate excretion.. Enalapril was given to rats (15 mg/kg/day) for seven days and to humans (10 mg twice daily) for 10 days. Blood and 24-hour urine samples were obtained in both groups. Renal cortical tissue from rats was analyzed for enzyme activity.. In rats, enalapril decreased urinary citrate excretion by 88%. The change in urinary citrate was not associated with a difference in plasma pH, bicarbonate nor potassium concentration. However, similar to metabolic acidosis and hypokalemia, enalapril caused a 42% increase in renal cortical ATP citrate lyase activity. When given to humans, enalapril significantly decreased urinary citrate excretion and urine citrate concentration by 12% and 16%, respectively, without affecting plasma pH or electrolytes.. Enalapril decreases urinary citrate in rats and humans. This is due, at least in part, to increases in cytosolic citrate metabolism through ATP citrate lyase in rats similar to that seen with chronic metabolic acidosis and hypokalemia. The effects of enalapril on urinary citrate and renal cortical ATP citrate lyase occur independently of acidosis or hypokalemia but may be due to intracellular acidosis that is common to all three conditions.

Topics: Acidosis; Adult; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Citric Acid; Enalapril; Female; Humans; Hypokalemia; Male; Rats; Rats, Sprague-Dawley

By using two similar dietary and pharmacological patterns of potassium depletive treatment, two experimental groups--KD2 (n = 6) and KD3 (n = 6)--with cumulative potassium deficit not significantly different, were obtained. The basal values of plasma potassium concentration and PRA, as well as the expression of renal hypokalemic dysfunction were not significantly different. Paired studies in the absence and presence of indomethacin (KD2 group) or enalapril (KD3 group) were performed. The aim of the research was evaluation of the effective roles of prostanoid and angiotensin (AT) II systems in renal hypokalemic dysfunction. The results show that: 1) AT II and cortical vasodilating prostanoids exerted opposite effects on the preglomerular arteriolar tone; 2) medullary prostanoids antagonized the vasopressin effects. Therefore, in potassium depletion the decreased synthesis of cortical and medullary prostanoids, in the face of the increased generation of AT II, contributed to reducing the glomerular filtration rate and facilitate the expression of vasopressin action. These components of the renal hypokalemic dysfunction probably exert a protective role with regard to the urinary chloride and potassium losses.

Topics: Angiotensin II; Chlorides; Creatinine; Diuresis; Enalapril; Female; Humans; Hypokalemia; Indomethacin; Kidney; Natriuresis; Potassium; Potassium, Dietary; Prostaglandins; Water

The glomerular size-selective properties in a patient with "hyponatremic hypertensive syndrome" were investigated before and after administration of the angiotensin-converting enzyme inhibitor enalapril. Hyponatremic hypertensive syndrome is a rare condition of renovascular hypertension characterized by electrolyte abnormalities (hyponatremia, hypokalemia), polyuria, and high renin activity. In this patient a marked increase in urinary protein excretion was observed. Treatment with enalapril normalized BP, corrected electrolyte abnormalities, and reduced proteinuria. Glomerular filtration rate (GFR), renal plasma flow (RPF), and the clearance of neutral dextrans of graded sizes were measured before and after 6 months of enalapril (20 mg/d) administration. Theoretical analysis of dextran and inulin clearance data with a model of glomerular size selectivity were adopted to separate effects of hemodynamic changes on macromolecule filtration from changes of intrinsic membrane selective properties. After enalapril urinary protein excretion decreased, GFR was unchanged and RPF almost doubled. Fractional clearance values of dextran molecules were markedly elevated in comparison with the corresponding values measured in a group of normal controls and were normalized by enalapril. Theoretical calculation of membrane pore characteristics showed that enalapril treatment reduced the radius of all membrane pores by approximately 1 nm. Altogether these results indicate that enalapril normalized glomerular filtration of neutral macromolecules and circulating proteins in a human condition of angiotensin II-induced proteinuria. Enalapril effectively restored glomerular size-selective function, reducing dimensions of membrane pores, independently of its effect on renal hemodynamics.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Dextrans; Enalapril; Glomerular Filtration Rate; Humans; Hypertension, Renovascular; Hypokalemia; Hyponatremia; Inulin; Kidney Glomerulus; Male; p-Aminohippuric Acid; Proteinuria

Seven patients with Bartter's syndrome were investigated before and after 3 months' treatment by enalapril. Serum potassium rose from 2.4 +/- 0.5 to 3.9 +/- 0.6 mmol/L. In all patients, serum magnesium rose and bicarbonate fell. Hormonal changes were as suspected: a further stimulation of renin and a decline in aldosterone. The BP sensitivity to angiotensin II normalized in the five patients in whom the test was performed. Clearance studies during maximal water diuresis, performed in four patients, were compatible with a high proximal fractional tubular sodium reabsorption and a relatively low distal fractional sodium reabsorption. Fractional free water excretion after furosemide was also low, confirming the concept of a primary sodium reabsorption defect in the furosemide-insensitive part of the nephron in Bartter's syndrome. The only consistent change after enalapril was a further decline in distal fractional sodium reabsorption. Initiation of therapy produced a BP fall in each subject. Clinical important hypotension associated with oliguria was seen twice, but these reactions were short-lasting. The BP rose to pretreatment values within 72 hours, despite continuation of converting-enzyme inhibition. Renal function recovered, though a moderate fall in function persisted. No other side effects were noticed. We conclude that converting-enzyme inhibition improves the potassium metabolism of patients with Bartter's syndrome, without ameliorating the abnormal renal sodium handling.

Topics: Adult; Bartter Syndrome; Electrolytes; Enalapril; Extracellular Space; Female; Humans; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Renin-Angiotensin System; Sodium

Total Body Potassium (TBK) was measured by whole body counting of 40K in 3 patients with Bartter's syndrome before, after 3 months and after 1 year of treatment with enalapril. In 2 patients TBK was found to be decreased before treatment, whereas TBK was within the normal range in the 3rd. During treatment serum potassium concentration and TBK increased in each subject and symptoms of fatigue and tetany disappeared. Enalapril is shown to be an effective treatment in Bartter's syndrome as it improves serum potassium, TBK and complaints.

Topics: Adult; Bartter Syndrome; Enalapril; Female; Follow-Up Studies; Humans; Hyperaldosteronism; Hypokalemia; Male; Middle Aged; Potassium

To investigate the determinants of mortality in patients with chronic congestive heart failure, we prospectively evaluated 84 patients with this disorder who underwent detailed biochemical, clinical, and functional tests at the time of initial evaluation and were then followed for 12 to 52 months (mean 31). During this period of follow-up, 58% of the patients died, of whom 71% died suddenly. The most important pretreatment predictor of mortality in these patients was the frequency of ventricular extrasystoles, followed by echocardiographic fractional shortening, a diagnosis of coronary artery disease, and duration of treadmill exercise. The finding of hypokalemia and hyponatremia in these patients at the time of entry into the study was associated with a poor prognosis by univariate analytical methods, but these electrolyte abnormalities did not provide independent prognostic information. The presence of ventricular arrhythmias was related to the severity of left ventricular dysfunction, exercise intolerance, and neurohormonal activation, suggesting that such arrhythmias are multifactorial in origin and may not simply be related to electrolyte abnormalities.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Captopril; Enalapril; Exercise Test; Female; Heart Failure; Heart Ventricles; Humans; Hypokalemia; Hyponatremia; Male; Middle Aged; Prognosis; Prospective Studies

Acute reversible renal failure with hyperkalemia developed in a 42-year-old woman during treatment of heart failure and hypertension with high doses of enalapril and diuretics. Creatinine clearance fell as low as 9 ml/min. Renal-artery stenosis and prerenal renal failure were excluded. Reduction in blood pressure in conjunction with reduced renal perfusion in heart failure can make glomerular filtration angiotensin dependent. Interruption of angiotensin II formation in this situation triggers off functional renal insufficiency.

Topics: Acute Kidney Injury; Adult; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Hypokalemia; Inulin; Kidney Function Tests; p-Aminohippuric Acid; Spironolactone

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Death, Sudden; Enalapril; Heart Arrest; Heart Failure; Humans; Hyperkalemia; Hypokalemia; Male; Middle Aged; Potassium; Resuscitation; Substance Withdrawal Syndrome