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  • 1
    ISSN: 1432-1041
    Keywords: Key words Phenprocoumon ; Thromboembolism prophylaxis; anticoagulant drugs ; age-dependence ; postoperative dosage requirement ; individual metabolism/sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: An enhanced response to warfarin and an increased risk of major bleeding has been observed in older patients. The reason for this increase in sensitivity remains unknown. It could be due to pharmacodynamic reasons, pharmacokinetic reasons, or both. Methods: We therefore followed an anticoagulant regimen with phenprocoumon in 19 older (76 years) and 19 younger patients (50 years) following heart valve replacement. INR values were determined frequently. At the 4th and around the 24th day after starting treatment with phenprocoumon, we also measured the total and unbound plasma concentration of phenprocoumon. Results: The dose requirement to obtain the desired anticoagulant effect was significantly lower in the older patients than in the younger patients (26.3 vs. 37.3 μg · kg−1 · day−1). The total plasma concentration (2.19 vs. 2.43 μg · ml−1), the percentage unbound drug in the plasma (0.61 vs. 0.64%) and the unbound plasma concentration (13.8 vs. 15.1 ng · ml−1) did not differ significantly between older and younger patients. The dose-adjusted INR (INR/dose) was higher in the older patients (110 vs. 67) but the INR adjusted for the unbound plasma concentration (INR/Cuss) which reflects the intrinsic sensitivity to the drug, was not significantly different (192 vs. 173). However, the older patients had an about 30% significantly lower metabolic clearance based on unbound drug (84 vs. 115 ml · kg−1 · h−1). Conclusions: Older patients (〉 70 years) require a dose approximately 30% lower than younger patients (〈 160␣years). Pharmacokinetic reasons (reduced metabolic clearance) are mainly responsible for the lower dose requirement of the older patients after heart valve surgery.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 95 (2000), S. I77 
    ISSN: 1435-1803
    Keywords: Key words Cardiovascular disease in women – coronary artery disease in women – menopause – risk factors – estrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiovascular disease, especially coronary artery disease (CAD), are leading causes of morbidity and mortality in women over the age of 50, whereas this is rarely the case in younger women. This fact, the overall lower incidence of and the 10–15 year retarded occurrence of CAD in women, has led to the controversially discussed question whether menopause is a risk factor for CAD. There has been universal agreement that surgically induced early menopause with bilateral oophorectomy is a risk factor for CAD, associated with a relative risk of 2, unless estrogen is replaced. Yet pertinent naturally occurring menopause studies showed variable results. This review focuses on the criteria required for an association to be accepted as a risk factor. The occurrence of natural menopause is influenced by preexisting risk factors in different, partly opposing ways. Smoking leads to an earlier occurrence of menopause, obesity, hypertension and diabetes to a later occurrence. These complex interactions complicate statistical analysis. Natural menopause is associated with profound biochemical and metabolic changes, which are established risk factors, e.g., increase in LDL and decrease in HDL cholesterol. These biochemical and metabolic changes are the mechanisms by which menopause can act as a risk factor. Conclusions: Menopause can be accepted as a risk factor, even if not all requirements, particularly that of reversibility, are fulfilled. The occurrence of menopause indicates the transition from a low to a higher risk for CAD in women.
    Type of Medium: Electronic Resource
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