trandolapril and Hypercholesterolemia

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.

Topics: Accidents; Antihypertensive Agents; Calcium Channel Blockers; Drug Combinations; Drug Overdose; Female; Forensic Toxicology; Humans; Hypercholesterolemia; Hypertension; Indoles; Kidney Failure, Chronic; Middle Aged; Verapamil

Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, beta blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p <0.01). Characteristics associated with risk for newly diagnosed DM included United States residence, left ventricular hypertrophy, previous stroke/transient ischemic attack, Hispanic ethnicity, coronary revascularization, hypercholesterolemia, greater body mass index, and higher follow-up systolic BP. Addition of trandolapril to verapamil SR decreased DM risk and addition of hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings associated with more severe vascular disease and Hispanic ethnicity identify a group at high risk for developing DM, whereas lower on-treatment BP and treatment with verapamil SR-trandolapril attenuated this risk.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Atenolol; Body Mass Index; Calcium Channel Blockers; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Follow-Up Studies; Hispanic or Latino; Humans; Hydrochlorothiazide; Hypercholesterolemia; Hypertrophy, Left Ventricular; Indoles; Ischemic Attack, Transient; Male; Myocardial Revascularization; Residence Characteristics; Risk Factors; Stroke; Systole; Verapamil