Drug interactions and toxicity.
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Digoxin↗
Biomedical subjects
H I Bussey
Publications and source records attributed to H I Bussey.
Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs.
BACKGROUND: The outcomes of an inception cohort of patients seen at an anticoagulation clinic (AC) were published previously. The temporary closure of this clinic allowed the evaluation of 2 more inception cohorts: usual medical care and an AC. OBJECTIVE: To compare newly anticoagulated patients who were treated with usual medical care with those treated at an AC for patient characteristics, anticoagulation control, bleeding and thromboembolic events, and differences in costs for hospitalizations and emergency department visits. RESULTS: Rates are expressed as percentage per patient-year. Patients treated at an AC who received lower-range anticoagulation had fewer international normalized ratios greater than 5.0 (7.0% vs 14.7%), spent more time in range (40.0% vs 37.0%), and spent less time at an international normalized ratio greater than 5 (3.5% vs 9.8%). Patients treated at an AC who received higher-range anticoagulation had more international normalized ratios within range (50.4% vs 35.0%), had fewer international normalized ratios less than 2.0 (13.0% vs 23.8%), and spent more time within range (64.0% vs 51.0%). The AC group had lower rates (expressed as percentage per patient-year) of significant bleeding (8.1% vs 35.0%), major to fatal bleeding (1.6% vs 3.9%), and thromboembolic events (3.3% vs 11.8%); the AC group also demonstrated a trend toward a lower mortality rate (0% vs 2.9%; P= .09). Significantly lower annual rates of warfarin sodium-related hospitalizations (5% vs 19%) and emergency department visits (6% vs 22%) reduced annual health care costs by $132086 per 100 patients. Additionally, a lower rate of warfarin-unrelated emergency department visits (46.8% vs 168.0%) produced an additional annual savings in health care costs of $29 72 per 100 patients. CONCLUSIONS: A clinical pharmacist-run AC improved anticoagulation control, reduced bleeding and thromboembolic event rates, and saved $162058 per 100 patients annually in reduced hospitalizations and emergency department visits.
Aged↗
Promising uses of calcium-channel blocking agents.
It is not surprising that calcium-channel blocking agents, which have numerous effects on various physiologic systems, have been employed for several "unapproved" uses. This manuscript reviews reports that have appeared within the last two years describing unapproved cardiovascular and noncardiovascular uses of the three available calcium-channel blocking agents. The cardiovascular uses discussed include hypertensive emergencies, pulmonary hypertension, congestive heart failure, aortic insufficiency, Raynaud's phenomenon, migraine headaches, antiplatelet effects and cardiac surgery. Areas of noncardiovascular use include muscular dystrophy, achalasia, esophageal spasm, dysmenorrhea, preterm labor, asthma, hyperuricemia, mania and depression and endocrinologic and oncologic conditions. While some of the data appear promising, other reports are conflicting and contradictory. Furthermore, because much of the information comes from poorly controlled trials or anecdotal reports, even the more promising uses must be studied further and compared with conventional therapy.
Aortic Valve Insufficiency↗
Update on calcium-channel blocking agents.
The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
Adolescent↗
Components of total parenteral nutrition solutions.
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Drug Interactions↗
Costs of oral anticoagulation treatment after myocardial infarction.
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Anticoagulants↗
How to monitor the dosage of warfarin.
To use and monitor warfarin therapy appropriately, the clinician must understand the pharmacodynamics and time profile of this agent and how the clotting cascade and coagulation inhibitor system are affected early in therapy. The redefined guidelines for PT monitoring require that the INR be used to monitor all patients receiving warfarin. Safety also requires that patients be monitored closely and that both the clinician and the patient be alert to potentially interacting variables. With long-term therapy, one must continually reassess the risk-to-benefit ratio of continuing therapy, changing the level of anticoagulation intensity, or discontinuing therapy. Finally, it is particularly important that patients understand the potential risks and benefits of anticoagulation therapy and how to monitor themselves. Patients should be encouraged to contact the appropriate clinician immediately with any questions that may influence the continued safe and effective use of warfarin.
Drug Interactions↗
A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements.
STUDY OBJECTIVE: To compare prothrombin time measurements by fingerstick and routine laboratory methods. DESIGN: Prospective cohort study. SETTING: University-affiliated anticoagulation clinic. PATIENTS: Thirty-three patients receiving warfarin with stable anticoagulation for 3 months preceding the two studies. INTERVENTIONS: Groups 1 (17 patients) and 2 (16 patients) provided 150 and 125 paired samples, respectively, for fingerstick and routine laboratory analysis. The fact that no patient required a dosage change allowed for a clinical assessment. MEASUREMENTS AND MAIN RESULTS: Correlation and agreement between methods were good in group 1 but poor in group 2. Fingerstick results were less variable (smaller standard deviation and smaller coefficient of repeatability) in both groups. By analysis of discrepant pairs (25 in group 1, 63 in group 2), the routine laboratory results indicated dosage changes erroneously more often than did the fingerstick method. CONCLUSIONS: In these two trials, the fingerstick system was superior to the routine laboratory method in that it was more reliable (less variability and more repeatable) and less likely to indicate dosage changes erroneously.
Anticoagulants↗
A review of enzyme induction of warfarin metabolism with recommendations for patient management.
We conducted a review of literature from the MEDLINE data base (1966-January 1997), and bibliographies of published articles, reviews, and letters to classify enzyme induction of warfarin metabolism interactions by onset, extent, and offset. Ten hepatic microsomal enzyme agents were assessed. Likelihood of interaction was based on the strength of supporting literature. Enzyme induction of warfarin metabolism by rifampin and barbiturates is considered likely, although the characteristics of the interactions are different. An interaction is probable with carbamazepine, griseofulvin, aminoglutethimide, nafcillin, and dicloxacillin. A suspected interaction may occur with smoking and long-term alcohol consumption. Ingestion of a small amount of alcohol is unlikely to interact with warfarin. The effect of phenytoin on warfarin metabolism is unpredictable. Anticipation of the expected time course and extent of interaction may allow for better therapeutic decisions and decrease the chance of inappropriate anticoagulation with its potential for complications.
Animals↗
Controversies in antithrombotic therapy for patients with mechanical heart valves.
Current anticoagulation guidelines for patients with mechanical heart valves are based on studies that are seriously flawed in that they used prothrombin time ratios rather than the international normalized ratio (INR) and failed to consider the level of anticoagulation actually achieved. Available data suggest that the appropriate INR range varies according to risk factors and that "tight control" of the INR is of critical importance in reducing thromboembolic and hemorrhagic events. Whether antiplatelet therapy adds benefit to an appropriately controlled level of anticoagulation is not clear. During pregnancy, warfarin is contraindicated; adjusted-dose heparin is recommended by published American and European guidelines. Even so, one small study suggests that this may be inadequate. Topical antifibrinolytic agents can negate the need to alter systemic anticoagulation during dental surgery.
Anticoagulants↗