Centers for Disease Control and Prevention. Chronic kidney disease CKD surveillance project. Miller S. Therapeutic drug monitoring in the geriatric patient.
Renal Pharmacotherapy: Dosage Adjustment Of Medications Eliminated By The Kidneys Paperback
In: Murphy J, ed. Clinical Pharmacokinetics , 5th Ed. Wallace J, Paauw DS. Appropriate prescribing and important drug interactions in older adults. Med Clin North Am ; — Farag A, et al. Dosing errors in prescribed antibiotics for older persons with CKD: a retrospective time series analysis.
Am J Kidney Dis ; — Aronoff GR, et al. Nyman HA, et al. Comparative evaluation of the Cockcroft-Gault equation and the modification of diet in renal disease MDRD study equation for drug dosing: an opinion of the nephrology practice and research network of the American College of Clinical Pharmacy. Pharmacotherapy ; — Stevens LA, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations.
Park EJ, et al. A systematic comparison of Cockcroft-Gault and modification of diet in renal disease equations for classification of kidney dysfunction and dosage adjustment. Ann Pharmacother ; — Dowling TD, et al.
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Glomerular filtration rate equations overestimate creatinine clearance in older individuals enrolled in the Baltimore longitudinal study on aging: impact on renal drug dosing. Ponticelli C, et al.
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Drug management in the elderly adults with chronic kidney disease: a review for the primary care physician. The absorption, distribution, metabolism, and excretion of many drugs are altered by impaired kidney function and aging and, when significant, are the foundation for the generation of drug dose adjustment strategies Table 1 12 — No consistent significant alterations in gut absorption have been reported in elderly CKD patients.
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The bioavailability of some drugs e. The volume of distribution of many hydrophilic drugs e. Decreased serum albumin is associated with increased unbound drug fraction and volume of distribution for phenytoin, furosemide, and ceftriaxone, among others. One should start with the typical dose and then monitor unbound drug concentrations or pharmacodynamic response to assure optimal patient outcomes. Drug metabolism may be reduced in elderly CKD patients as the result of reductions in liver blood flow and the intrinsic activity of cytochrome oxidative enzymes.
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Emerging clinical evidence suggests that accumulation of uremic toxins may be responsible for the activity of cytochrome oxidative enzymes and transporter proteins Prediction of the degree of effect of aging or CKD on the metabolism of a particular drug is problematic because there is no quantitative correlation even among drugs within the same pharmacologic class. In addition to physiologic reductions in glomerular filtration, tubular secretion may be impaired and contribute to marked reductions in renal drug clearance.
The elderly and those with CKD stages 3 to 5 are also more prone to acute kidney injury from drugs that cause direct damage or alter renal hemodynamics e. Given that the measurement of GFR or creatinine clearance is challenging and costly, eCrCl should be used to guide therapeutic decisions, and for drugs with a narrow therapeutic index, monitoring serum drug concentrations is recommended.
Drug dosing recommendations for the most frequently prescribed and highest-cost drugs for Medicare beneficiaries and for other commonly prescribed medications in the elderly are listed in Table 3 5 , 6 , The key to optimize elderly CKD patient outcomes is for clinicians to understand the rationale for drug dose adjustment and to use the appropriate resources to individualize therapy. The concomitant presence of obesity or malnutrition or of other chronic diseases that affect drug pharmacokinetics and response such as heart failure and liver disease further complicates therapy decisions and patient outcomes.
Centers for Disease Control and Prevention. Chronic kidney disease CKD surveillance project. Miller S. Therapeutic drug monitoring in the geriatric patient. In: Murphy J, ed. Clinical Pharmacokinetics , 5th Ed. Wallace J, Paauw DS.
Appropriate prescribing and important drug interactions in older adults. Med Clin North Am ; — Farag A, et al. Bland and Altman plots showing the within-person differences between the estimated creatinine clearance obtained by using the Cockcroft-Gault equation and estimated glomerular filtration rate obtained by using A the Modification of Diet in Renal Disease equation and B the Chronic Kidney Disease Epidemiology Collaboration.
The solid line indicates the mean difference, and the dashed line indicates limits of agreement. The percentage discordance for the 3 NOACs was also calculated to quantify the implication of using the different methods for estimating kidney function on drug therapy Figures 3A-C. Among the overall study population, the discordance in dabigatran dosage according to kidney function categories was The lowest discordance was observed for apixaban 1.
Discordances in dosing of new oral anticoagulants as a function of estimated glomerular filtration rate equations.
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Discordance rates for the Modification of Diet in Renal Disease equation and chronic kidney disease epidemiology collaboration equations compared with recommended dosing based on the Cockcroft-Gault equation. A: dabigatran. B: rivaroxaban. C: apixaban. The discordance in dabigatran dosage was The lowest discordance was observed for apixaban, being 3.
Drug Dosing in the Elderly with Chronic Kidney Disease | Kidney News
In patients with renal function impairment, the lowest discordance was observed for apixaban, being 2. Data are expressed as No.
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Secondly, when these equations are used instead of CG equation, the discordances were higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Thirdly, most discordances were linked to an overestimation of renal function. The GFR is predominantly estimated in clinical practice from many estimating equations. The MDRD equation provides more accurate estimates of GFR than the CG equation 18 and is now widely reported by clinical laboratories around the world whenever serum creatinine is reported. These findings agree with several retrospective studies in more than 20 patients with chronic kidney disease, reporting that the use of the MDRD equation overestimates creatinine clearance, leading to significantly higher drug doses compared with doses calculated by using CG equation.
Accordingly, we also found that most discordances were related to an overestimation of renal function in this subgroup of patients.. According to our findings, a previous analysis of more than patients with AF in primary care showed that there would be clinically important potential risks when prescribing dabigatran or rivaroxaban if the MDRD formula was used instead of CG, especially in elderly patients. For rivaroxaban, 0. Both dabigatran doses mg and mg displayed efficacy consistent with the overall trial relative to warfarin across the range of renal function in terms of the primary outcome of stroke or systemic embolism.
Interestingly, apixaban was the exception, as we found the lowest discordance between the 2 methods with this drug. A substudy of the ARISTOTLE trial 39 on renal dysfunction showed that the percentage of patients with renal impairment was similar independently of the used method of assessment, although no comparisons were made.
Differences between equations for estimating kidney function and drug dosing will always exist. Therefore, regardless of the equation used, clinical judgment must prevail. When presented with different kidney function estimates that potentially translate into different drug dosing regimens, clinicians must choose the regimen that optimizes the risk-benefit ratio given the patient-specific clinical scenario.
When estimating equations are not expected to provide accurate measures of kidney function, it may be reasonable to obtain an accurately timed urine collection to calculate measured creatinine clearance.. The limitations of the present study include the small number of patients with severe renal dysfunction in the study population, which may have led to higher concordance than that expected in a population with a higher prevalence of severe chronic kidney disease.
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