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Biomedical subjects

K A Stringer

Publications and source records attributed to K A Stringer.

32 records · Page 2Linked to original sources
PubMed1991

The effect of pirmenol administration on the anti-coagulant activity of warfarin.

The effect of administration of pirmenol, an extensively metabolized and plasma protein-bound antiarrhythmic agent, was evaluated in ten patients on chronic warfarin therapy. After a 3-week baseline period and 7 days of placebo administration, patients received 150 mg of oral pirmenol every 12 hours for 14 days. Prothrombin time was determined during the baseline and placebo periods, during pirmenol administration, and 14 days after the last pirmenol dose (washout). There was no significant difference between mean baseline, placebo, pirmenol, and washout prothrombin times. Coadministration of pirmenol does not appear to affect the anticoagulant activity of warfarin.

Administration, Oral↗
PubMed1990

Anistreplase: a novel thrombolytic agent for acute myocardial infarction.

Anistreplase, a modified congener of streptokinase, is a recently approved thrombolytic agent used in the treatment of acute myocardial infarction (AMI). Clinical studies have demonstrated anistreplase to be equally efficacious as intracoronary streptokinase when given within four hours of the onset of chest pain. Thirty units, given as a single bolus intravenous injection, result in reperfusion rates of approximately 60-70 percent. The adverse-effect profile of anistreplase compares favorably with that of streptokinase, with hemorrhagic complications being the most serious. Anistreplase has two distinct advantages over both streptokinase and alteplase: (1) it can be administered as a single bolus intravenous injection and (2) it has a longer half-life which may result in decreased reocclusion rates. Anistreplase therapy is associated with reductions in both short- and long-term mortality and has been shown to preserve left ventricular function. A large, long-term, comparative clinical trial (Third International Study of Infarct Survival or ISIS-III) investigating morbidity and mortality rates with streptokinase, alteplase, and anistreplase is ongoing, as is a direct comparative study against alteplase alone (TEAM-3, Multicenter Thrombolytic Trials of Eminase in Acute Myocardial Infarction).

Anistreplase↗
PubMed1989

The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers.

In a randomized cross-over study the effect of verapamil on the pharmacokinetics of theophylline was evaluated in eight cigarette smoking male volunteers. Theophylline was administered as an intravenous infusion of aminophylline, 6 mg/kg based on ideal body weight, over 30 minutes in the control phase. In the treatment phase, aminophylline was administered after a four day regimen of oral verapamil 80 mg every 8 hours. Serial blood samples were collected over a 24 hour period following aminophylline administration. Theophylline serum concentrations were determined by a fluorescence polarization immunoassay, the Abbott TDxR. Theophylline clearance decreased by 11.5%, from a mean (+/-SD) of 1.39 +/- 0.38 mL/min/kg in the control phase to 1.23 +/- 0.21 mL/min/kg with the co-administration of verapamil (P = 0.104). Theophylline elimination rate constant decreased by approximately 9.4% from 0.171 +/- 0.032 to 0.155 + 0.023 hr-1 during the treatment phase (P = 0.085). The area under the curve (AUCo alpha) and volume of distribution at steady-state (Vss) for theophylline were also not statistically different between the two study phases. These results are inconsistent with those of other investigators and the relevance of a potential theophylline-verapamil drug interaction remains unclear.

Adult↗
PubMed1989

Streptokinase-induced anaphylaxis.

Streptokinase is a thrombolytic agent used most commonly for the dissolution of thrombi obstructing coronary arteries during acute myocardial infarction (MI). Anaphylactic reactions induced by streptokinase occur rarely. We report the case of a patient with acute MI who developed anaphylaxis shortly after the initiation of an intravenous infusion of streptokinase. The patient became profoundly hypotensive and developed an erythematous rash that spread rapidly to cover most of his body. He required mechanical ventilation and the administration of epinephrine for blood pressure support, which succeeded after dopamine and norepinephrine had failed. Streptokinase-induced anaphylaxis is thought to be mediated by immunoglobulin E (IgE), and patients who develop this adverse reaction have been shown to have higher serum concentrations of IgE to streptokinase than those who do not. Epinephrine is the agent of choice for the management of hypotension associated with anaphylaxis. Little evidence exists to support the routine pretreatment of patients who are to receive streptokinase with corticosteroids and/or antihistamines. Streptokinase skin testing may be a useful and accurate means of identifying patients at risk for streptokinase-induced anaphylaxis. Further investigation is required to determine the appropriateness of skin testing in streptokinase therapy.

Anaphylaxis↗
PubMed1988

Enhanced pirmenol elimination by rifampin.

The potential for drug-drug interaction between pirmenol, an extensively metabolized antiarrhythmic agent, and rifampin, a potent inducer of hepatic drug-metabolizing enzymes, was evaluated in 12 healthy adults. After administration of a single 150-mg oral dose of pirmenol on day 1, pirmenol plasma and urine concentrations were determined for 72 hours postdose. On days 4 through 17, subjects received 600 mg of rifampin once daily. On day 15, subjects were given a second single 150-mg oral dose of pirmenol concomitantly with rifampin, and plasma and urine concentrations were again determined. Coadministration of rifampin with pirmenol resulted in significant (P less than .005) changes in pirmenol pharmacokinetic parameters. A sixfold decrease in pirmenol AUC and sevenfold increase in the apparent plasma clearance of pirmenol were found. Elimination half-life decreased more than twofold. Based on these findings, pirmenol dosage adjustment will be required when pirmenol is given to patients concurrently receiving rifampin. These results suggest that the administration of pirmenol with other agents that induce hepatic enzymes may result in accelerated pirmenol clearance.

Adult↗
PubMedDate not supplied

Verapamil preceded by calcium in supraventricular tachycardia.

Verapamil has been shown to be effective in the management of supraventricular tachycardia (SVT). However, the utility of verapamil may be limited because of adverse effects, specifically hypotension. Several clinical observations have shown that the intravenous administration of calcium is effective in reversing the myocardial depressant effects of verapamil. We report the case of a patient with SVT and a systolic blood pressure of 80 mm Hg in which the administration of calcium chloride prior to that of verapamil may have negated verapamil-induced hypotension.

Calcium↗
PubMedDate not supplied

Biochemical and pharmacologic comparison of thrombolytic agents.

The number of thrombolytic drugs for the management of acute myocardial infarction is rapidly expanding. New agents, some of which are biochemically modified versions of currently available thrombolytics, will soon arrive in the marketplace. The pharmacologic differences of the new drugs are the basis for clinical differences such as enhanced clot lysis and prolonged elimination half-life. Ultimately, these features may result in improved infarct artery patency and patient survival.

Amino Acid Sequence↗
PubMedDate not supplied

Thrombolytic therapy for acute myocardial infarction.

Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.

Adjuvants, Pharmaceutic↗
PubMedDate not supplied

TIMI grade flow, mortality, and the GUSTO-III trial.

Thrombolytic therapy dates back to animal studies performed in the early 1940s, although clinical trials did not begin until the early 1980s. Many large, placebo-controlled trials conclusively recorded improved survival with thrombolytics in the treatment of acute myocardial infarction. However, only recently did clinical trials compare tissue plasminogen activator (tPA) and streptokinase (SK), and only one study showed a difference in mortality between them. This discrepancy, in part, led to the open-artery hypothesis that early and sustained infarct-related artery patency improves outcome. This theory was tested in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) study. The angiographic substudy of GUSTO-I provided strong evidence for the relationship between 90-minute thrombolysis in myocardial infarction (TIMI) grade 3 flow and lower mortality. However, despite significantly higher 90-minute TIMI grade 3 flow (54% vs 32%) with accelerated tPA versus SK plus intravenous heparin, the absolute difference in mortality rate was less than 1%. The recently completed GUSTO-III trial compared accelerated tPA with reteplase (rPA). Based on the open-artery hypothesis and previous data showing an absolute difference of 15% in 90-minute TIMI grade 3 flow between the agents, it was anticipated that mortality would be lower with rPA than with accelerated tPA. The GUSTO-III study showed no significant difference in 30-day mortality for the agents (7.47% vs 7.24%, p=0.61), respectively. These results raise questions about the validity of the hypothesis: if 90-minute TIMI grade 3 flow is such a strong predictor of mortality, why is there not a greater difference in mortality rates for thrombolytic agents?

Coronary Angiography↗