Drugs in kidney diseases

Drugs in kidney diseases DrNoushin Hashemi.M.D. NephrologistDrugs and the Kidney1- Renal Physiology and Pharmacokinetics2- Drugs and the normal kidney3- Effect of renal disease on drug metabolism4- Drugs toxic to the kidney5- Prescribing in kidney disease3Normal Kidney Function 1 Extra Cellular Fluid Volume control2 Electrolyte balance3 Waste product excretion4 Drug and hormone elimination/metabolism5 Blood pressure regulation6 Regulation of haematocrit7 regulation of calcium/phosphate balance(vitamin D3 metabolism)Clinical Estimation of renal functionClinical examinationpallor, volume status, blood pressure measurement, urinalysisBlood testsRoutine Testshaemoglobin levelelectrolyte measurement (Na ,K , Ca, PO4)urea

Serum Creatinine and GFRMuscle metabolite- concentration proportional to muscle massHigh: muscular young menLow: conditions with muscle wastingElderlyMuscular dystrophyAnorexiaMalignancywomen

Normal range 70 to 140 mol/litre

GFR EstimationCockroft-Gault FormulaCrCl=Fx(140-age)xweight/CreaP F=1.04F=1.23MDRD FormulaEPI(race,age,gender,cr)Estimation of GFRCreatinine Clearance

Crt clearance =Urine crt Urine volumePlasma crtCrt clearance =(140-AGE) WEIGHT 72 Crt.(Cockcroft-Gault equation) Tests of renal function cont.24h Urine sample-Creatinine clearancegold standard Inulin clearance urea understimate and cr overestimate GFR

Pharmacokinetics

AbsorptionDistributionMetabolismElimination filtration secretion FarmacodynamicComplex interactions of other farmacologic factors including drugconcentration,receptor-drug interaction and effect on body chemistry and clinical factors such as concurrent disease and degree of organ dysfunctionDrugs and normal kidney

Effects of renal disease on drugs

Effect of uremia on drug disposition 1-Bioavalability : uremia decreases GI absorption of drugs (dissolution ,alkalinization,first pass hepatic metabolism , impaire protein binding) 2-Distribution:-edema and ascites :increase volume of distribution -dehydration and muscle wasting :decrease volume of distribution -combination of decrease serum Alb concentration and reduction in Alb affinity reduce protein binding in uremia 3-Metabolism: -uremia slows the rate of reduction and hydrolysis reactions . -uremia alter the deposition of drugs metabolize by liver through changes in plasma protein binding.AcetaminophenAngiotensin-converting enzyme inhibitorsAngiotensin receptor blockersAdriamycinAllopurinolAmiodaroneAmoxapineAzathioprineBenzodiazepines-BlockersBupropionBuspirone

TABLE 57-2 --Drugs That Have Active or Toxic Metabolites in Dialysis PatientsCardiac glycosidesClorazepateCephalosporinsChloral hydrateClofibrateDesipramineDiltiazemEncainideEsmololH2-blockersHydroxyzineImipramineIsosorbideLevodopaLorcainide MeperidineMetronidazoleMethyldopaMiglitolMinoxidilMorphineNitrofurantoinNitroprussideProcainamidePrimidoneTABLE 57-2--Drugs That Have Active or Toxic Metabolites in Dialysis Patients cont..PropoxyphenePyrimethamine QuinidineSerotonin reuptake inhibitorsSpironolactoneSulfonylureasSulindacThiazolidinedionesTriamtereneTrimethadioneVerapamilVidarabineEffect of dialysis on drugs: Drug clearance during dialysis : -Adsorption -Convection -Diffusion drugs that have small volume of distribution more effectively removed by dialysis Effect of dialysis on drugsMolecular weightWater solubilityDegree of protein bindingMembrane clearanceDrugs with MW >500 daltons poorly cleared by conventional HD membranes.Protein or tissue binding or lipid soluble are not dialyzed properly.(