Drug Clearance and Renal Replacement Therapy Quiz

Drug Clearance and Renal Replacement Therapy

• Continuous renal replacement therapy (CRRT) relies on ultrafiltration of plasma water to remove ultrafilterable drugs, using membranes with larger pore sizes and involving convective transport of solute.
• CRRT can remove larger molecules (up to 5000 daltons) but is limited by protein binding and device filtration rate, which determine the rate of removal.
• Sieving coefficients allow calculation of drug loss if the ultrafiltration flow rate is known, with a coefficient closer to 1.0 indicating more passage across the filter.
• Drug clearance from the body involves renal excretion, extrarenal pathways, and metabolism, impacting drug removal in critically ill patients.
• Total clearance in patients undergoing extracorporeal treatment is the sum of extracorporeal, no renal, and residual renal clearance, complicating dose modification calculations.
• Cytochrome P450 enzyme activities play a crucial role in drug clearance and metabolite formation, with species differences being important to consider in drug metabolism research.
• Liver and kidney function dictate drug metabolism and elimination, with impaired liver function in obesity and higher renal clearance in obese patients without kidney failure.
• Pediatric drug dosing considerations include differences in renal function, plasma protein levels, and water-soluble drug distribution compared to adults.
• Nephrotoxic medications should be avoided in pediatric patients when possible, and creatinine elevation should prompt a review of all medications and considerations for accurate GFR assessment.
• Drug clearance on CRRT depends on ultrafiltration rate and molecular characteristics of the medication, such as molecular weight, charge, volume of distribution, water solubility, and protein binding.
• Drug clearance by the kidney involves glomerular filtration, active secretion, and metabolism, with uptake and secretion processes mediated by specific transporters and proteins in the proximal tubule cells.
• The kidney has significant CYP activity and is involved in drug metabolism via Phase II reactions, with secretion of conjugated drugs and amphiphatic molecules occurring across specific membrane proteins.

Drug Elimination and Clearance

• Drug elimination refers to the irreversible removal of drugs from the body through excretion and biotransformation processes.
• Excretion involves the removal of intact drugs through various routes, such as renal excretion, bile, sweat, saliva, milk, or expired air for volatile drugs.
• Biotransformation, mainly occurring in the liver, chemically converts drugs into metabolites through enzymatic processes, with some drugs also undergoing nonenzymatic changes.
• Drug excretion and metabolism involve complex rate processes within the body's organs, with specific functions and varying elimination processes in different tissues.
• Four classes of transporters - multidrug resistant protein (MRP), organic anion transporter (OAT), organic cation transporter (OCT), and P-glycoprotein (Pgp) - play crucial roles in drug transport mechanisms in the kidney proximal tubule and hepatic cells.
• Hepatic drug clearance is influenced by hepatic blood flow, the amount of free drug in the blood, and hepatic clearance of the unbound drug, with alterations in presystemic metabolism and hypoalbuminemia affecting drug clearance.
• Renal elimination of drugs involves glomerular filtration, active tubular secretion, and passive tubular excretion, with nutritional status impacting medications primarily renally filtered and excreted.
• Protein-energy malnutrition (PEM) can result in decreased cardiac function, affecting renal and hepatic perfusion, and reducing renal elimination and hepatic drug clearance.
• Enteral or parenteral nutrition (PN), particularly the protein component, improves the systemic clearance of susceptible drugs in undernourished patients transitioning from unfed to fed states.
• In young children, hepatic metabolic clearance is influenced by maturational changes in drug-metabolizing enzymes, hepatic blood flow, plasma protein binding, and active transport processes.
• Maturational changes in the determinants of hepatic metabolic clearance are most pronounced in the first months and years of life, with significant interindividual variability in the youngest age ranges.
• Understanding the ontogeny of drug-metabolizing enzymes is crucial for the appropriate use of certain drugs in young children, with limited knowledge on the maturational processes influencing hepatic drug clearance.