Elsa-Grace V. Giardina

Benefits, adverse effects and drug interactionsof herbal therapies with cardiovascular effects

Because the use of herbal therapies in the U.S. is escalating, it is essential to be aware of clinical and adverse effects, doses and potential drug-herb interactions. A consumer poll in 1998 indicated that one-third of respondents use botanical remedies, and nearly one in five taking prescription medications also used herbs, high-dose dietary supplements or both. An estimated 15 million adults are at risk for potential adverse interactions involving prescription medications and herbs or vitamin supplements, yet most practicing physicians have little knowledge of herbal remedies or their effects. Herbal products are marketed without the proof of efficacy and safety that the Food and Drug Administration (FDA) requires of drugs. The Dietary Supplement and Health Education Act of 1994 allocates responsibility to manufacturers for ensuring safety and efficacy with no specific requirements to submit documentation. Manufacturers may state a products physiologic effects but may not make claims for the treatment or cure of specific diseases. Consumers and practitioners have little information about product safety, contraindications, interactions or effectiveness and are reliant on manufacturers to provide accurate labeling. Recently, the growing number of foods with herbs has raised concerns at the FDA, which requires evidence that food additives are safe. Considering that the growing appeal of herbal remedies is likely to continue, physicians, particularly cardiologists, must become familiar with the available cardiovascular information on herbs. This review highlights the existing data on the efficacy, adverse effects and interactions for herbal therapies that impact on the cardiovascular system.

Intermittent Intravenous Procaine Amide to Treat Ventricular Arrhythmias: Correlation of Plasma Concentration with Effect on Arrhythmia, Electrocardiogram, and Blood Pressure

Abstract Twenty patients with ventricular arrhythmias were treated with procaine amide to determine an antiarrhythmic plasma drug concentration range and to observe procaine amides effect on blood...

The Effect of Quinidine and Other Oral Antiarrhythmic Drugs on Serum Digoxin: A Prospective Study

We compared the effects of quinidine and three alternate antiarrhythmic drugs on serum digoxin concentration in 63 patients before and during administration of quinidine, procainamide, disopyramide, or mexiletine. Quinidine increased digoxin concentration by at least 0.5 nmol/L in 21 of 22 patients: Mean serum digoxin rose from 1.2 nmol/L to 2.4 nmol/L (P less than 0.001). Procainamide, disopyramide, or mexiletine increased serum digoxin by 0.5 nmol/L in one of 41 patients. Anorexia, nausea, and vomiting develop soon after starting quinidine therapy in 10 of the 22 patients who received quinidine but in only five of the 41 patients who received procainamide, disopyramide, or mexiletine (P less than 0.01). Quinidine prolonged the PR intervals from 160 +/- 14 ms to 183 +/- 26 ms, but procainamide, disopyramide, and mexiletine did not change the PR interval (P less than 0.005). In digitalized patients, quinidine increases serum digoxin concentration, increases digoxins effect on atrioventricular conduction, and produces more adverse gastrointestinal effects than procainamide, disopyramide, or mexiletine.

Antiarrhythmjc effect of imipramine hydrochloride in patients with ventricular premature complexes without psychological depression

A study was performed in cardiac patients without psychological depression to determine (1) the antiarrhythmic efficacy of imipramine, (2) its half-life of elimination and duration of action, and (3) the frequency of adverse effects. Twenty-two patients with 30 or more ventricular premature complexes/hour entered the protocol. A drug-free and a placebo day were followed by dosing with imipramine, 1 mg/kg per day, given in two divided doses. The dose was increased by 1 mg/kg per day every other day until ventricular premature complexes were suppressed by at least 80 percent, adverse drug effects were encountered or a total daily dose of 5 mg/kg per day was given. Each day a 24 hour continuous electrocardiogram was recorded to determine the frequency of ventricular premature complexes and heart rate. During the acute dose-ranging period, 18 patients (82 percent) had an antiarrhythmic effect from imipramine. Two patients received 5 mg/kg per day without any decrease in the frequency of ventricular premature complexes. The half-life of elimination of imipramine (parent compound) was 8.8 +/- 3.72 hours but its duration of action was much longer. Four patients (18 percent) had treatment discontinued because of troublesome adverse effects during a follow-up period of 19 +/- 8.8 months. It is concluded that imipramine is a potent antiarrhythmic drug with a long duration of action and relatively few major adverse effects.

Effects of Desipramine on Autonomic Control of the Heart

OBJECTIVE To assess the effects of desipramine (DMI) on autonomic control of the heart. METHODS Blood pressure, RR interval (the time between successive heart beats), and RR interval variability, a noninvasive measure of autonomic control of the heart, were assessed in 13 subjects younger than 30 years old. RESULTS DMI treatment was associated with an increase in blood pressure, a decrease in RR interval, and a decline in low and high frequency RR interval variability. CONCLUSIONS These preliminary data suggest that, in young people, DMI treatment produces a substantial decrease in parasympathetic input to the heart and an increase in the ratio of sympathetic to parasympathetic input, changes that in certain circumstances have been associated with an increased risk of arrhythmia. In exploring the cardiac effects of the tricyclic antidepressants (TCAs) in young people, the impact of TCAs on autonomic input to the heart should be examined.

The antiarrhythmic effect of nortriptyline in cardiac patients with ventricular premature depolarizations

The effect of nortriptyline against ventricular arrhythmias was determined in 16 cardiac patients with 30 or more ventricular premature depolarizations per hour. Nortriptyline was administered orally, 0.5 mg/kg body weight per day, and increased by 0.5 mg/kg per day every third day until ventricular premature depolarizations were suppressed (greater than or equal to 80%), adverse effects occurred or a total daily dose of 3.5 mg/kg per day was given. Each patient had daily 24 hour continuous electrocardiograms, 12 lead standard electrocardiograms and physical examination; blood pressure was measured in the supine and standing position four times a day. Each patient also had radionuclide angiography at rest to measure ejection fraction before and at the effective or maximal dose. Thirteen patients (81%) had an antiarrhythmic response and 11 met the study criterion of at least 80% improvement. Doses ranged from 50 to 200 mg/day (mean 111 +/- 45), steady state plasma concentration ranged from 46 to 410 ng/ml (mean 153 +/- 96) and half-life of elimination of nortriptyline was 4 to 22 hours (mean 13 +/- 4). Administration of nortriptyline did not depress mean ejection fraction (before 42 +/- 12%, after 41 +/- 12%); it was associated with an orthostatic decrease in systolic blood pressure (mean -13 +/- 13 mm Hg). Nortriptyline is an effective antiarrhythmic agent which may be given twice a day even in patients with impaired ventricular function.

Oral conjugated equine estrogen increases plasma von Willebrand factor in postmenopausal women

OBJECTIVES We sought to test whether one month of daily oral conjugated equine estrogen (CEE) or transdermal estradiol alters hemostatic factors in postmenopausal subjects. BACKGROUND Estrogen replacement therapy and hormonal replacement therapy (HRT) effect an early increase in cardiovascular events in postmenopausal women. Circulating plasma von Willebrand factor (vWF) antigen is a marker of generalized endothelial dysfunction and atherothrombosis. METHODS Thirty-eight healthy postmenopausal women (average 59 +/- 7 years) were randomized to receive daily oral CEE, 0.625 mg (n = 21); transdermal estradiol, 0.1 mg/day (n = 7); or oral placebo (n = 10) for one month. Blood samples were collected at baseline and after two weeks and four weeks of therapy for measurement of circulating plasma hormones, lipid concentrations, and hemostatic factors. RESULTS Oral CEE decreased total cholesterol (p < 0.01) and low-density lipoprotein cholesterol (p < 0.01), although it increased both triglycerides (p < 0.05) and high-density lipoprotein cholesterol (p < 0.01). Transdermal estradiol had no significant effect on lipids. Plasminogen activator inhibitor-1 antigen declined in both oral CEE and transdermal estradiol users, but did not achieve statistical significance. Fibrin D-dimer antigen did not vary significantly in any group. However, oral CEE users had a significant increase in vWF from baseline to four weeks (p < 0.03) and a decrease in tissue-type plasminogen activator antigen from baseline to four weeks (p < 0.004), which was significantly different from the change observed in the transdermal estradiol group (p < 0.05). CONCLUSIONS These data suggest that the oral CEE-mediated increase in plasma vWF may have clinical relevance given the early atherothrombotic effects of HRT in postmenopausal women.

Imipramine binding to alpha‐1‐acid glycoprotein in normal subjects and cardiac patients

The relationship between binding ratio of Imipramine and plasma α1‐acid glycoprotein (AAG) was determined in normal subjects, patients with chest pain syndrome, and patients after myocardial infarction. Binding ratio of Imipramine was determined by equilibrium dialysis and plasma AAG concentration was determined by radial immunodiffusion. Plasma AAG concentrations ranged from 56 to 80 mg/dl (X̄ = 65 ± 9 mg/dl) in 12 normal subjects, from 86 to 228 mg/dl (X̄ = 125 ± 37 mg/dl) in 12 patients with chest pain syndrome, and from 78 to 350 mg/dl (X̄ = 181 ± 69 mg/dl) in 12 patients after myocardial infarction. Plasma AAG concentrations in the three patient groups differed. Binding ratio ranged from 5.6 to 19.8 (X̄ = 12 ± 3.5). Binding ratio of Imipramine significantly correlated with plasma AAG concentration, but not with plasma albumin. In addition, binding ratio of Imipramine and pure AAG was significantly related, indicating AAG is an important determinant for Imipramine binding. If plasma AAG concentration increases or changes rapidly, plasma drug concentration and drug effect may be unpredictable. Under these circumstances an estimate of free drug fraction may be clinically helpful and can be estimated from the formula ȳ = 7.95 +0.03 × AAG.

Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation

Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability.

Outcomes of Comprehensive Heart Care Programs in High-Risk Women

OBJECTIVE The purpose of this study was to improve the fund of knowledge, reduce cardiovascular disease (CVD) risk, and attain Healthy People 2010 objectives among women in model womens heart programs. METHODS A 6-month pre/post-longitudinal educational intervention of high-risk women (n = 1310) patients at six U.S. womens heart programs consisted of comprehensive heart health counseling and use of American Heart Association/American College of Cardiology (AHA/ACC) Evidence-Based Guidelines as enhancement to usual care delivered via five integrated components: education/awareness, screening/risk assessment, diagnostic testing/treatment, lifestyle modification/rehabilitation, and tracking/evaluation. Demographics, before and after knowledge surveys, clinical diagnoses, laboratory parameters, and Framingham risk scores were also determined. Changes in fund of knowledge, awareness, and risk reduction outcomes and Healthy People 2010 objectives were determined. RESULTS At 6 months, there were statistically significant improvements in fund of knowledge, risk awareness, and clinical outcomes. Participants attained or exceeded >90% of the Healthy People 2010 objectives. Proportions of participants showing increased knowledge and awareness of CVD as the leading killer of women, of all signs and symptoms of a heart attack, and calling 911 increased significantly (11.1%, 25.4%, and 34.6%, respectively). Health behavior counseling for physical activity, diet, and diabetes as CVD risk factors increased significantly (28.3%, 28.2%, and 12.5%, respectively). There was a statistical 4.1% increase in participants with systolic blood pressure (SBP) <140/90 mm Hg, a 4.7% decrease in participants with total cholesterol (TC) >240 mg/dL, a 4.5% decrease in participants with TC >200 mg/dL, a 5.9% decrease in participants with high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, a 4.4% decrease in participants with HDL-C <40 mg/dL, and an 8.8% increase in diabetics with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. CONCLUSIONS CVD prevention built around a comprehensive heart care model program and AHA/ACC Evidence-Based Guidelines can be successful in improving knowledge and awareness, CVD risk factor reduction, and attainment of Healthy People 2010 objectives in high-risk women. Thus, these programs could have a dramatic and lasting impact on the health of women.