Clinical Pharmacodynamics: Principles of Drug Response and Alterations in Kidney Disease

Clinical Journal of the American Society of Nephrology : CJASN
Frieder Keller, Alexander Hann

Abstract

Pharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is foun...Continue Reading

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Citations

Dec 4, 2019·Expert Opinion on Drug Metabolism & Toxicology·Seung Hwan LeeJong Hwan Sung
Jul 3, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Mark A Perazella, Thomas D Nolin
Apr 3, 2019·Clinical Journal of the American Society of Nephrology : CJASN·David H Ellison

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