Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-agonists have found wide clinical use as racemic mixtures for 20 years, but information on their pharmacokinetics is not comprehensive. They are well absorbed orally, but have low systemic availability due to extensive first-pass sulphation. When administered by inhalation, very little of the administered dose reaches the lungs, but the small amount that does produces effective bronchodilatation. Plasma protein binding of most beta-agonists is negligible, and there is substantial extravascular distribution of the administered dose. Elimination of intravenous drug is predominantly renal, whereas oral doses are mostly eliminated by biotransformation. Renal clearance correlates with creatinine clearance; therefore, dose reduction should be considered if renal function is impaired, such as in the elderly or in cardiac failure. The elimination half-life of most beta-agonists is relatively short, and pharmacokinetics are independent of dose and duration of treatment. Differences in the pharmacokinetics of the enantiomers are evident. There is very large variation in pharmacodynamic response for a given plasma beta 2-agonist concentration among different subjects, and as treatment proceeds in an individual subject. Therefore, in most cases therapeutic response and side effects are more useful for the monitoring of beta 2-agonist treatment than measurement of plasma drug concentrations. The pharmacokinetics of beta 2-agonists are not greatly altered in pregnancy although these agents cause a marked reduction in maternal renal function. Placental transfer is relatively rapid, and side effects are observed in fetus and neonate. Elimination may be somewhat faster in children (8 to 15 years) than in young adults. Asthma does not appear to influence the pharmacokinetics of beta 2-agonists; the only recorded drug interaction of clinical significance is an increase in theophylline clearance by intravenous isoprenaline (isoproterenol). Controlled release oral preparations do not reduce side effects, but may improve compliance due to less frequent dosing. The application of pharmacokinetic principles may improve the clinical usage of beta-agonists, at least when they are used in premature labour and in cardiac failure.
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PMID:Clinical pharmacokinetics of beta-agonists. 196 85

Non-compliance has a major influence on the successful outcome of a therapeutic regimen. It also unnecessarily increases the costs of health care. In a study involving 137 outpatients receiving digoxin 55 patients (40%) were found to be non-compliant. Patients who experienced communication problems and who lacked a meaningful relationship with their doctor showed a marked deterioration in compliance. An applied pharmacokinetic approach was used to predict the serum digoxin concentration for each patient. The creatinine clearance was determined and the degree of severity of heart failure was assessed. Total body clearance was then calculated. The predicted concentration was also calculated and compared with the measured digoxin concentration enabling an objective assessment of compliance. Twenty-four of the non-compliant patients who had subtherapeutic levels of digoxin (less than 0.8 ng/ml) had signs of cardiac failure. Eighteen of these patients were receiving additional medication (1.7 +/- 0.5 items) for the treatment of cardiac failure.
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PMID:Quantifying non-compliance in patients receiving digoxin--a pharmacokinetic approach. 199 86

We prospectively studied the relationship between serum creatinine and survival among 492 elderly subjects admitted for stroke and monitored for a mean period of 18 months post-stroke. In multivariate proportional hazards models, serum creatinine remained an independent predictor of mortality (P = 0.0001) after accounting for other important predictors such as level of consciousness. Mini-Mental State Score, age, leucocyte count, presence of heart disease, diabetes, heart failure, atrial fibrillation and use of cardiovascular medication. This association between elevated serum creatinine and mortality was also found in patient subgroups with CT-proven infarction and intracerebral haematoma. It is concluded that serum creatinine is an independent predictor of survival after stroke. Further studies are required to confirm this relationship and to elucidate the underlying mechanism.
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PMID:Serum creatinine: an independent predictor of survival after stroke. 199 42

In 33 patients with heart failure (NYHA II-III) the 24-h blood pressure was examined during the titration of two ACE-inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc.. All patients received an additional therapy either with captopril (group A, n = 17) or enalapril (group B, n = 16) in random order. Serum-electrolytes, serum- and urine-creatinine, and plasma-renin- activity were measured before and during therapy with both ACE-inhibitors. 24-h blood pressure measurements were taken before and on the first and fifth days of the treatment with ACE-inhibitors. Neither group was different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate. The mean initial dose of captopril was 9.2 +/- 1.2 mg which was titrated to a mean daily dose of 40.7 +/- 3.3 mg given three-times daily. Each patient of group B received an initial dose of 2.5 mg enalapril and a mean maintenance dose of 8.4 +/- 0.9 mg once daily. The first dose effect on blood pressure was similar with captopril and enalapril with a maximal decrease of systolic and diastolic blood pressure of 8/8 mmHg (after 1 h) in group A and of 9/7 mmHg (after 4 h) in group B. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p less than 0.005) but heart rate was not significantly affected by either ACE-inhibitor. Neither group differed significantly during ACE-inhibition in their 24-h blood pressure and heart rate profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Enalapril versus captopril in heart failure--effect on blood pressure and kidney function]. 202 41

The long-term prognosis in severe congestive heart failure is very poor. Therapeutic regimens, in order to improve prognosis, should directly or indirectly influence the compensatory systems that are activated, ACE-inhibitor therapy has emerged as an important regimen in this context. In the CONSENSUS-trial (3), we could demonstrate that the addition of enalapril to conventional therapy in severe CHF significantly improved survival. The experience from this study forms the background for the recommendations in this work. 253 patients with severe heart failure (New York Heart Association (NYHA) Classification functional class IV) were randomized at 35 Scandinavian centers to placebo (n = 126) or enalapril (n = 127), in addition to their conventional therapy. The treatment dose of enalapril varied between 2.5 and 40 mg daily (man 18.3 mg). Blood samples for measurement of serum electrolytes and serum creatinine were taken repeatedly during follow-up. There seems to be about a 10% increase in creatinine within 2 weeks of initiating enalapril therapy. This increase seems to be independent of baseline creatinine level. Adverse experience regarding serum creatinine was reported in 22 placebo-treated patients and in 51 patients in the enalapril group. This reporting was based upon the investigators' feelings of significant importance of the observation and not on symptomatology. This was the main reason for permanent withdrawal in 2 and 7 patients, respectively. During initiation of enalapril therapy the blood pressure response is important after the very first dose, but for renal function the response may not appear until several days later. However, in most patients there are no problems with starting enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ACE-inhibition on renal function in severe congestive heart failure. 202 43

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.
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PMID:[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung]. 204 Dec 50

1. Population pharmacokinetic parameters of quinidine were determined based on 260 serum drug concentration measurements in 60 patients treated for arrhythmias with quinidine sulphate or quinidine bisulphate (Kinidin duriles) orally. 2. Quinidine kinetics were best described by a two compartment model with zero order absorption from the gastrointestinal tract. The pharmacokinetics are influenced by severe heart or liver failure and renal function impairment. No effect was found for mild or moderate heart failure, for age, for body weight or for coadministration of nifedipine. 3. Population pharmacokinetic parameters of quinidine (assuming 100% bioavailability of oral quinidine sulphate) were: nonrenal clearance for patients without severe heart and liver failure 12.6 l h-1, reduction in patients with severe heart or liver failure to 6.8 l h-1, renal clearance (l h-1) related to creatinine clearance (ml min-1), proportionality constant 0.0566, volume of distribution of the central compartment 161 l, maximum serum drug concentration 1.4 h after administration of quinidine sulphate and 6.0 h after administration of quinidine bisulphate. 4. The results were validated by predicting the serum drug concentration in a separate group of 30 patients. The model reliably predicted both the population average and the variability of the serum concentration of quinidine. 5. Using Monte Carlo computer simulations, an a priori dosing regimen was derived that should maximize the proportion of patients having quinidine serum concentrations within the recommended range (2-5 mg l-1): initial dose of 600 mg quinidine sulphate in all patients, 3 h later first maintenance dose of quinidine bisulphate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Population pharmacokinetics of quinidine. 205 69

We studied, by 48-hour Holter monitoring, 33 patients with chronic stable heart failure (radionuclide ejection fraction less than 35%), complex ventricular arrhythmias and no electrolyte abnormalities, after a period during which they were treated with digoxin and diuretics. Before Holter monitoring blood samples were analyzed for serum concentration of sodium, potassium, magnesium, urea, creatinine, digoxin, aldosterone and for plasmatic renin activity in addition to urinary aldosterone and catecholamines determination. After these investigations in 23 patients, 5-20 mg of enalapril were progressively added to the conventional therapy, while 10 patients continued the previous therapy. After 8 weeks 30 patients were subjected to a second 48-hour Holter monitoring and to the same biochemical and hormonal tests. One patient died and 2 were lost to follow up. Only the enalapril group showed a significant decrease in the number of premature ventricular complexes (PVC) (p less than 0.01), and the frequency of couplets and episodes of ventricular tachycardia (VT) declined significantly (P less than 0.01). In the two groups there were no significant changes in digoxin, sodium, or magnesium, while potassium concentration increased in both groups (p less than 0.01). In the enalapril group heart rate and systolic and diastolic pressure declined significantly (p less than 0.01), and New York Heart Association class (NYHA) improved (p less than 0.001). In the other group there were no significant changes in these parameters. Enalapril caused a significant increase in the plasmatic renin activity (p less than 0.01) and a significant fall of plasma and urinary aldosterone (p less than 0.01; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of complex ventricular arrhythmias after enalapril treatment in patients with advanced stable heart failure. 205 78

Conditions like heart failure that augment the activity of neurohumoral mechanisms i.e. the renin-angiotensin systems, sympathetic nerve activity and vasopressin secretion are commonly associated with a decreased effective blood volume and a reduced renal perfusion. This leads to an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis as a vasodilator and natriuretic counter-regulating system. We investigated the role of prostaglandins in renal functional control in an experimental setting of congestive heart failure by chronic inhibition of cyclooxygenase by indomethacin. In chronic moderate heart failure plasma levels of prostaglandin E2 and prostacyclin were unchanged whereas the urinary excretion of prostaglandin E2 was significantly increased, indicating an augmented synthesis within the kidney (Figures 1 to 3). After inhibition of prostaglandin synthesis we observed a profound increase of renal vascular resistance associated with a reduction of effective renal plasma flow and renal blood flow. This was mainly due to a constriction of the vas afferens of the glomerulum. This led to an impairment of renal function indicated by an increase of serum creatinine and blood urea nitrogen associated with a reduction of urinary flow and fluid retention (Figures 4 and 5). We also studied in a randomized, double-blind, placebo-controlled, parallel-group trial in 40 patients with congestive heart failure effects of acetylsalicylic acid (500 mg t.i.d.) on renal functional parameters. In patients with normal sodium intake acetylsalicylic acid reduced urinary prostaglandin E2 concentration by 37% which led to a reduction of daily urinary sodium excretion by 29% in comparison to placebo (Figure 6). These results clearly show the importance of vasodilator prostaglandins in the regulation of kidney function in heart failure where inhibition of cyclooxygenase results in profound deterioration of renal perfusion and kidney function and retention of fluid and sodium.
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PMID:[Role of prostaglandins in regulation of kidney function in heart failure]. 206 53

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure. 213 69


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