warfarin and Bradycardia

Patients with complex medical and drug histories are becoming more commonplace in dental practice. This article reviews three serious adverse drug interactions that are well supported by the literature and can impact dental practice. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the renal excretion of lithium and lead to lithium toxicity. Metronidazole and fluconazole inhibit the metabolism of warfarin by blocking cytochrome P-450 2C9 (CYP-2C9), the major metabolic pathway of warfarin, with the end result being dramatic increases in patients' international normalized ratios (INRs) and potentially fatal bleeding. Propranolol and other nonselective beta-adrenergic blocking agents can inhibit the vasodilatory effect of epinephrine in dental local anesthetic solutions, leading to hypertensive reactions and a concomitant reflex bradycardia. It is important for clinicians to recognize and avoid these serious drug interactions. By doing so, they will provide the safest and best treatment for their patients.

Topics: Adrenergic beta-Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Bradycardia; Cytochrome P-450 CYP2C9; Dental Care; Drug Interactions; Epinephrine; Fluconazole; Hemorrhage; Humans; International Normalized Ratio; Lithium; Metronidazole; Propranolol; Warfarin

To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group.. 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat.. Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively).. During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bradycardia; Cardiac Pacing, Artificial; Chronic Disease; Confidence Intervals; Female; Humans; Incidence; Male; Middle Aged; Regression Analysis; Risk Factors; Sick Sinus Syndrome; Syndrome; Tachycardia, Supraventricular; Telemetry; Thromboembolism; Warfarin

The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma half-life of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-1) (P less than 0.02). Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case.

Topics: Administration, Oral; Bradycardia; Cimetidine; Drug Eruptions; Drug Interactions; Half-Life; Humans; Hypotension; Injections, Intravenous; Kinetics; Protein Binding; Prothrombin Time; Random Allocation; Stereoisomerism; Vitamin K 1; Warfarin

Warfarin is known to interact with many drugs and can lead to serious consequences. We report a case of 52 years old female patient from Himachal Pradesh. During hospital stay patient developed coagulopathy in form of INR above 10 and bradycardia with ventricular rate on ECG with digoxin level of 3.76 ng/ml. In this way digoxin toxicity was confirmed and it was considered as cause of coagulopathy after ruling out interactions of warfarin.

Topics: Bradycardia; Digoxin; Drug Interactions; Female; Humans; Middle Aged; Warfarin

We report here the successful treatment of a 16-year-old female who ingested 20 tablets of digoxin each containing 0.25 mg (total dose ingested equivalent to 0.1 mg/kg), 32 tablets of warfarin each containing 5mg (equivalent to 3.2 mg/kg), and approximately 15 tablets of propafenone each containing 300 mg (equivalent to 90 mg/kg). The patient developed hypotension and sinus bradycardia necessitating external cardiac pacing 17 hours after drug ingestion. In addition to gastric lavage, activated charcoal, blood alkalinisation, administration of vitamin K and temporary cardiac pacing, the authors performed plasma exchange for drug removal and administered rifampicin in order to increase the metabolism of digoxin, propafenone and warfarin. The patient was discharged without any sequelae. Plasma exchange may be lifesaving in drug ingestions where there is a low volume of distribution and high plasma protein binding. Rifampicin, an inducer of cytochrome p450, may be used in intoxications for elimination of drugs with inactive metabolites.

Topics: Adolescent; Anti-Arrhythmia Agents; Anticoagulants; Bradycardia; Cytochrome P-450 Enzyme System; Digoxin; Drug Overdose; Enzyme Induction; Female; Humans; Hypotension; Plasma Exchange; Propafenone; Rifampin; Warfarin

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Coronary Care Units; Electrocardiography; Female; Humans; Male; Middle Aged; Morphine; Myocardial Infarction; Oxygen Inhalation Therapy; Retrospective Studies; Shock, Cardiogenic; Tachycardia; Time Factors; Warfarin