Biomedical subjects

F P Zeller

Publications and source records attributed to F P Zeller.

13 recordsLinked to original sources

PubMed1988

Alteplase: a tissue plasminogen activator for acute myocardial infarction.

Alteplase is a human tissue plasminogen activator (t-PA) produced by recombinant DNA technology. It is a relatively fibrin-specific thrombolytic agent, used primarily to lyse coronary artery clots. It has proven effective in the treatment of acute myocardial infarction (AMI). Despite continuous reevaluation of pharmacokinetic parameters for t-PA, limited distribution and clearance data mandate administration of t-PA as a continuous infusion. Tissue plasminogen activator is eliminated primarily by hepatic metabolism with an elimination half-life of five to ten minutes. Plasma levels show great interindividual variation but correlate with infusion rate and decrease in fibrinogen level. The current recommended dose is 100 mg administered as a 10-mg iv bolus followed by a continuous infusion over three hours. However, 40-150 mg has been used in clinical trials. The compound has undergone extensive testing, comparing it with placebo and streptokinase (SK), and combining it with angioplasty and coronary artery bypass surgery. Tissue plasminogen activator is effective at opening clotted coronary arteries in approximately 70 percent of AMI patients and has been shown to be approximately twice as effective as SK in one U.S. trial. Although there is considerable evidence of efficacy with t-PA, data evaluating the influence of t-PA on mortality are limited, but suggest a reduction to five percent. Currently, thrombolytic therapy is indicated for patients experiencing a transmural AMI with onset of symptoms within three to six hours before presenting to the emergency room. Active internal bleeding or conditions predisposing to serious hemorrhage are contraindications to thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1987

The use of intravenous dipyridamole in thallium 201 myocardial perfusion imaging.

Thallium 201 myocardial perfusion imaging is a standard method of evaluating regional myocardial blood flow. Myocardial perfusion is best evaluated at rest and during exercise, however, alternative methods have been sought to increase coronary blood flow in patients incapable of performing adequate exercise. A promising new method is the use of intravenous dipyridamole for pharmacologic stress imaging. It has distinct advantages over traditional treadmill exercise testing. The primary advantage of combining intravenous dipyridamole and thallium 201 is for testing patients in whom exercise is impractical or contraindicated. Examples include patients taking beta blockers and those who have had myocardial infarction or have severe peripheral vascular disease. To date, this agent has been available only to clinical investigators in approved protocols. With continued success, it should be approved for general use in the near future.

Coronary Circulation↗

PubMed1987

Bepridil: a new long-acting calcium channel blocking agent.

Bepridil is an investigational calcium channel blocking agent with antianginal activity that has a distinct and complex pharmacologic profile. Bepridil produces significant coronary vasodilation and modest peripheral effects, in addition to negative inotropic and chronotropic effects. Bepridil favorably modifies both myocardial oxygen demand and supply, supporting its use as an antianginal drug. Electrophysiologically, bepridil exhibits classes I, III, and IV antiarrhythmic activity. Five U.S. trials evaluating the short-term antianginal efficacy of bepridil collectively reported that bepridil causes significant improvement in both subjective and objective parameters of efficacy without depressing left ventricular function. In addition, one U.S. trial reported continued antianginal effects of bepridil after long-term use. There are limited data comparing and/or combining bepridil with other antianginal drugs, but the available information is promising. Limited information also exists on the use of bepridil in acute myocardial infarction and arrhythmias. Tolerance to bepridil therapy has been excellent, with the most common adverse effects being diarrhea and dizziness. It is unclear whether bepridil will be used as a first-line agent in the treatment of chronic stable angina pectoris; however, its long half-life, which makes once daily dosing possible, is certainly a significant advantage.

Angina Pectoris↗

PubMed1987

Tolerance to organic nitrates in ischemic heart disease.

The development of tolerance to organic nitrates in patients with ischemic heart disease is reviewed, with particular interest in alterations to both the hemodynamic and antiischemic effects over time. The article primarily focuses on how tolerance is defined, what biochemical mechanisms are involved when this condition occurs, which agents have been associated with the development of tolerance, and what can be done to prevent or reverse the condition in patients taking nitrates for ischemic heart disease. From a historical perspective, tolerance to organic nitrates has been a recognized phenomenon since the last century. The role that blood-level determinations and nitroglycerin pharmacokinetics have in the development of tolerance is discussed, and an extensive overview of currently marketed organic nitrate preparations and a few others available only through approved investigational protocols is presented. The role of cross-tolerance is discussed as is the role that nitrate-free intervals play in partially or completely reversing the effects of tolerance during chronic nitrate therapy. Additionally, a discussion of which specific nitrate formulation are least likely to have tolerance associated with their use is included, such as short-acting nitrate formulations with the exception of the intravenous dosage form. Finally, buccal nitroglycerin is presented as another new formulation that appears to be associated with minimal tolerance in studies already completed.

Coronary Disease↗

PubMed1987

Controversies in the use of transdermal nitroglycerin systems.

The role of transdermal nitroglycerin (TNTG) in the treatment of ischemic heart disease and congestive heart failure (CHF) is reviewed, with an emphasis on controversies concerning efficacy, hemodynamics, and dosing. Currently marketed rate-controlled transdermal nitroglycerin systems provide steady plasma concentrations of nitroglycerin for 24 hours. However, results of controlled trials in ischemic heart disease and CHF have raised doubts about the ability of TNTG to exert clinically important antianginal or hemodynamic benefit for the full 24-hour period. There is evidence that the duration of effect after TNTG application may persist for 24 hours, but there also is evidence of a lack of efficacy beyond 6 to 12 hours. This issue has not been resolved, but there is a trend toward use of larger doses that produce more persistent effects. The effects of conventional doses of TNTG in ischemic heart disease are modest; efficacy is based on demonstrated improvements in exercise performance. High TNTG doses (40-90 mg/24 hours) are required by many patients. In CHF, TNTG improves venous hemodynamic measurements. A dose-response relationship is not well defined. High-dose TNTG therapy is probably required to increase cardiac output and decrease systemic vascular resistance. Nitrate attenuation appears to be an important phenomenon with TNTG therapy. As with other forms of nitrate therapy, adverse effects may be a limiting factor, and clinical experience with high-dose TNTG therapy is limited. For some patients, TNTG therapy is an important addition to medical therapy. Further studies are needed to confirm reported improvements in exercise performance and hemodynamic benefits and to identify patient subsets likely to benefit from TNTG therapy.

Administration, Topical↗

PubMed1986

Lower incidence of doxorubicin-induced cardiomyopathy by once-a-week low-dose administration.

A review of the literature investigating an alternative method of administering doxorubicin on a weekly basis demonstrates a lower incidence of doxorubicin-induced cardiomyopathy, as judged by endomyocardial biopsy techniques and by an apparent lower incidence of CHF as compared to older reports in the literature utilizing conventional tri-weekly administration. However, none of these studies has utilized objective methods for verifying cardiac function. The precise reason why weekly administration may induce lesser degrees of damage to the myocardium is not clearly understood. However, it appears that the lower serum concentrations obtained with this dosing regimen result in lower myocardial tissue concentrations of the drug. Though the initial data are encouraging, larger clinical trials are necessary to establish a lower incidence of cardiotoxicity with weekly low-dose doxorubicin administration. Such studies, if specifically designed to evaluate changes in myocardial function, will resolve the questions and hopefully establish the advantages of this encouraging new therapeutic modality.

Animals↗

PubMed1986

Early use of beta-adrenergic-blocking agents in acute myocardial infarction.

Of recent interest is the acute use of beta-adrenergic-blocking agents in patients who have suffered an acute myocardial infarction (AMI). Acute use of beta-blockers refers to initiation of therapy within hours following the onset of symptoms suggestive of AMI. The proposed goal of therapy is to alter the infarction process to improve mortality. Because of the hyperadrenergic activity present in patients during an infarction, beta-blockers are theoretically an attractive therapeutic intervention because of their sympatholytic properties. Acute use of beta-blockers has been shown to limit infarct size, as determined by cardiac enzyme activity, and reduce the incidence of major ventricular arrhythmias. Beta-blockers may also prevent infarction in patients with symptoms suggestive of infarction. However, the acute use of beta-adrenergic-blocking agents has not been shown to reduce short-term (less than or equal to 30 d) mortality. In view of this fact, the acute use of beta-adrenergic-blocking agents cannot be recommended.

Adrenergic beta-Antagonists↗

PubMed1986

Compatibility of intravenous drugs in a coronary intensive care unit.

In a coronary intensive care unit (CCU) it is often necessary to utilize extensive pharmacologic interventions and multiple intravenous medications in order to stabilize a critically ill patient. However, the necessity of several intravenous infusions often presents the problem of compatibility of these medications when infused within a common line. The pharmacist must possess adequate skill to identify potential incompatibilities by retrieving information on the physical and chemical compatibilities of various intravenous medications. In a critical care setting, time is an important factor, and information that can be obtained rapidly and reliably is vital for the pharmacist to prevent the administration of an irritating substance or a medication that has undergone deterioration as a result of chemical inactivation. A compatibility table containing the most commonly used drugs in a CCU has been developed based on currently available literature, including standard reference texts, about these medications. The table outlines the potential for interactions, within a single intravenous line, when several drugs are infused concurrently. In addition, a review of the concepts of physical and chemical incompatibility is presented. The stability of an admixture is defined utilizing requirements established in the USP NF monographs and manufacturers' specifications. The resulting table concisely organizes vital information in a form that allows rapid, accessible information to the pharmacist in a critical care setting, where it is most needed.

Chemistry, Pharmaceutical↗

PubMed1986

Current concepts in clinical therapeutics: acute myocardial infarction.

The epidemiology and etiology, pathophysiology, diagnosis, clinical presentation, complications, and treatment of acute myocardial infarction (AMI) are reviewed. Major risk factors for AMI include age, sex (men greater than women), family history, race, hyperlipidemia, hypertension, cigarette smoking, diabetes mellitus, and diet. AMI occurs when there is a prolonged decrease in oxygen supply to the myocardium caused by coronary thrombosis or coronary vascular spasm. Traditional drug treatment of uncomplicated AMI includes oxygen, laxatives, and analgesics. For analgesia, narcotic agonists are generally preferred, although intravenous nitroglycerin is of value for both reducing infarct size and relieving pain. Fibrinolytic therapy is also indicated in these patients. Low-dose heparin should be initiated on admission to the hospital. Beta-adrenergic blocking agents have proven useful in reducing the incidence of ventricular fibrillation and sudden death. Antiplatelet agents may also be used to decrease long-term mortality. Recent studies have focused on reduction of infarct size using agents such as beta blockers, calcium-channel blockers, nitroglycerin, and thrombolytics. Revascularization procedures are required in some patients to re-establish adequate coronary perfusion. Most patients who survive AMI initially have a relatively uncomplicated clinical course. An increasing number of therapeutic interventions are available for acute and chronic treatment of AMI.

Arrhythmias, Cardiac↗

PubMedDate not supplied

Acceptance of transcutaneous nitroglycerin patches by patients with angina pectoris.

The acceptance, preference, and side effects of the 3 commercially available nitroglycerin patches were examined in 30 patients with chronic, stable angina pectoris. Patients were serially interviewed after each treatment period regarding patch comfort, aesthetics, discomfort upon removal, adhesiveness, efficacy, and side effects. They were also interviewed and examined for adverse skin reactions. There were significant differences among the 3 patches with respect to comfort, aesthetics, discomfort, and adhesiveness. Skin reactions (mostly mild) occurred in 83% of patients: patch A, 70%; patch B, 43%; and patch C, 57%. Intolerable reactions, which would have caused patch discontinuation, were noted in 40% of patients: patch A, 30%; patch B, 7%; and patch C, 10%. Most patients had an intolerable reaction to only 1 patch. Significant differences were present only between patches A and B with respect to total and intolerable skin reactions. Thus the systems differed in terms of patient preference and skin reactions. Skin reactions are probably more prevalent than previously reported but usually occur with just one of the patches. Physicians and hospitals should probably individualize nitrate patch therapy within formulary and budgetary constraints.

Adhesiveness↗

PubMedDate not supplied

Fish oil: effectiveness as a dietary supplement in the prevention of heart disease.

The low incidence of reported heart attacks and cardiovascular-related deaths in Greenland Eskimos and the Japanese has generated interest in the possible protective effect of their diet, which is made up primarily of fish and related marine foods. This paper reviews the current evidence for reducing the risk of cardiovascular disease with fish-oil supplementation, and discusses related clinical data to support the mechanisms proposed. Included is evidence that fish oil can lower certain serum lipid levels, prolong bleeding time, and reduce systolic blood pressure when consumed in moderately large doses. Information on safety and side effects is also presented, such as a possible increase in serum cholesterol levels and annoying side effects that may severely limit widespread use of this food supplement. Presently it remains unanswered whether fish oil should be recommended as a dietary supplement for the prevention and/or treatment of hypercholesterolemia and associated coronary artery disease. Further research is required to demonstrate a clear reduction in cardiovascular mortality before a uniform recommendation can be made.

Blood Pressure↗

PubMedDate not supplied

Lovastatin for hypercholesterolemia.

Lovastatin is the first 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of primary hypercholesterolemia. It is indicated as adjunctive therapy to dietary control and should be initiated at 20 mg/d in the evening. With higher dosages, twice-daily dosing is preferred, particularly when the dosage reaches the maximum recommended 80 mg/d. Compared with other drugs available, lovastatin has been shown to have good efficacy and a low incidence of side effects. Limited pharmacokinetic information available from the manufacturer reports absorption approximately 30 percent, protein binding greater than 95 percent, and a dual pathway for elimination through both urine (10 percent) and feces (83 percent). The drug has been clinically tested versus placebo and in combination with other cholesterol-lowering drugs. Lovastatin is effective in lowering total cholesterol and low-density lipoprotein cholesterol by 25-30 percent, with nonfamilial (hypercholesterolemic) patients responding better than those with the familial form of the disease. One percent of lovastatin patients have discontinued therapy because of intolerable side effects. The most common complaints are flatulence and diarrhea; more severe abnormalities include elevation of liver enzymes and an unclear propensity for producing lens opacities. The monthly cost to a patient taking 20 mg/d is approximately $44. Although the drug should be added to hospital formularies, long-term safety experience and competition from other HMG-CoA reductase inhibitors will determine lovastatin's final therapeutic role.

Humans↗

PubMedDate not supplied

Effect of caffeine on the oral absorption and disposition of quinidine.

The effect of caffeine on the oral absorption and disposition of quinidine was assessed in nine healthy men. Single 300-mg doses of quinidine sulfate were given by mouth in the absence and presence of caffeine in a crossover study. In the caffeine-treatment phase, 1 g of caffeine was given per day in divided doses for one week before the administration of a second 300-mg quinidine sulfate dose. Blood samples were collected at various times for 24 hours after drug administration, and the sera were assayed for quinidine. Urine specimens were also analyzed for quinidine. No differences were found in the quinidine absorption and disposition constants between the control and caffeine-treated phases, using a nonlinear, least-squares regression analysis of the serum quinidine concentration-time curves and standard blood and urine bioavailability test methods. The hypothesis proposed by previous investigators that quinidine disposition may be altered by caffeine-inducible hepatic microsomal enzymes was not supported by these data. Caffeine treatment at a daily dose of 1 g per day for one week had no apparent effect on the absorption or disposition of quinidine after a single 300-mg oral dose of quinidine sulfate in healthy men.

Adult↗