drugs & kidney

8/3/2019 Drugs & Kidney

1/18

Dr. Sumit Kr. GhoshDr. Sumit Kr. GhoshAsst. ProfessorAsst. Professor

Department of MedicineDepartment of Medicine

Medical College & Hospital, KolkataMedical College & Hospital, Kolkata


2/18

INTRODUCTIONINTRODUCTION

Renal Physiology and PharmacokineticsRenal Physiology and Pharmacokinetics

Drugs and normal kidneyDrugs and normal kidney

Drugs toxic to kidneyDrugs toxic to kidney

Prescribing drugs in kidney diseasesPrescribing drugs in kidney diseases


3/18

RENAL PHYSIOLOGYRENAL PHYSIOLOGY

1. Extra Cellular Fluid Volume control1. Extra Cellular Fluid Volume control

2. Electrolyte balance2. Electrolyte balance

3. Waste product excretion3. Waste product excretion

4. Drug and hormone elimination/metabolism4. Drug and hormone elimination/metabolism5. Blood pressure regulation5. Blood pressure regulation

6. Regulation of haematocrit6. Regulation of haematocrit

7. Regulation of calcium/phosphate balance7. Regulation of calcium/phosphate balance

(vitamin D3 metabolism)(vitamin D3 metabolism)


4/18


5/18

Renal ExcretionRenal Excretion

Total amount of excretion of a drug depends onTotal amount of excretion of a drug depends on

1)1) Glomerular filtration:Glomerular filtration:

~ plasma protein binding~ plasma protein binding~ renal blood flow~ renal blood flow

2)2) Tubular reabsorptionTubular reabsorption

~ lipid solubility~ lipid solubility

~ ionization~ ionization

3)3) Tubular secretionTubular secretion

active transport of organic acids & basesactive transport of organic acids & bases

If renal clearance of a drug >120ml/min (GFR), additional tubularIf renal clearance of a drug >120ml/min (GFR), additional tubularsecretion can be assumed to be occurringsecretion can be assumed to be occurring


6/18

DRUGS & NORMAL KIDNEYDRUGS & NORMAL KIDNEY

Diuretics:Diuretics:

-- LoopLoop

-- ThiazideThiazide-- Aldosterone antagonistAldosterone antagonist

-- OsmoticOsmotic

Antidiuretics


7/18

Indications for use of diureticsIndications for use of diuretics

Heart failure ( acute or chronic )Heart failure ( acute or chronic ) Pulmonary oedemaPulmonary oedema

HypertensionHypertension

Nephrotic syndromeNephrotic syndrome

HypercalcaemiaHypercalcaemia


8/18

Loop

Thiazide

Amiloride


9/18

DRUGS TOXIC TO KIDNEYDRUGS TOXIC TO KIDNEY

(NEPHROTOXIC DRUGS)(NEPHROTOXIC DRUGS) Drug related renal pathology can affect any / all kidney compartmentsDrug related renal pathology can affect any / all kidney compartments

1) Tubulointerstitium is commonly involved, best known examples1) Tubulointerstitium is commonly involved, best known examples

NSAID and antibioticsNSAID and antibiotics

-- drugs should be considered in all primary tubulointerstitial diseasesdrugs should be considered in all primary tubulointerstitial diseases

2) Glomeruli2) Glomeruli3) Vasculature (only infrequently affected)3) Vasculature (only infrequently affected)

-- mimicks many primary renal diseasesmimicks many primary renal diseases

Mechanism:Mechanism: -- immunologically mediatedimmunologically mediated

-- toxic/ischemic damagetoxic/ischemic damage

dose is important for the laterdose is important for the later

Dose dependent vs IdiosyncraticDose dependent vs Idiosyncratic


10/18

Patterns of Drug-induced Lesions

Tubulointerstitium

Acute tubular injury

- Osmotic nephrosis

- Nephrocalcinosis

- Chrystal NP

Acute interstitial

nephritis

Chronic tubulointer-

stitial nephropathy

Glomeruli

Minimal change

disease

Focal segmental

glomerulosclerosis

Membranous GN

Crescentic GN

Thrombotic micro-angiopathy

Blood vessels

Hyalinosis

Thrombotic micro-angiopathy

Vasculitis


11/18

TubuloTubulo--

interstitiuminterstitium

GlomeruliGlomeruli Blood vsBlood vs

NSAIDNSAID

ACEACE--II

Antibiotics

Antibiotics

LithiumLithium

DiazepamDiazepam

BisphosphonateBisphosphonate

CisplatinCisplatinMethotrexateMethotrexate

NSAIDNSAID

LithiumLithium

BisphosphonateBisphosphonatePropyithiouracilPropyithiouracil

CisplatinCisplatin

Mitomycin CMitomycin C

TamoxifenTamoxifen

ClopidogrelClopidogrel

QuinineQuinine

PhenytoinPhenytoinSulfasalazineSulfasalazine

PropyithiouracilPropyithiouracil

Mitomycin CMitomycin C

PenicillaminePenicillamine


12/18

PRESCRIBING DRUGS INPRESCRIBING DRUGS IN

KIDNEY DISEASESKIDNEY DISEASES

Patients with renal impairmentPatients with renal impairment

Patients on DialysisPatients on Dialysis

Patients with renal transplantsPatients with renal transplants


13/18

Clearance of drugs that are primarily excretedClearance of drugs that are primarily excretedunchanged (aminoglycosides, digoxin) isunchanged (aminoglycosides, digoxin) isreduced parallel to decrease in CrCLreduced parallel to decrease in CrCL

Loading dose of such a drug is not alteredLoading dose of such a drug is not altered

but maintenance doses should be reducedbut maintenance doses should be reduced

or dose interval prolonged proportionatelyor dose interval prolonged proportionately

Rough guide:Rough guide:CrCL (ml/min)CrCL (ml/min) dose to be reduced bydose to be reduced by

5050--70 1.5times70 1.5times3030--50 2 times50 2 times

1010--30 3 times30 3 times

55--10 6 times10 6 times


14/18

Dose rate of drugs, partly excreted unchanged inDose rate of drugs, partly excreted unchanged inurine also needs reduction, but to lesser extenturine also needs reduction, but to lesser extent

Plasma proteins, esp albumin, are often low orPlasma proteins, esp albumin, are often low oraltered in structure in patients with renal diseasesaltered in structure in patients with renal diseases

binding of acidic drugs is reduced but not that ofbinding of acidic drugs is reduced but not that ofbasic drugsbasic drugs

Permeability of BBB is increased in renal failurePermeability of BBB is increased in renal failure

-- Sedatives causes more CNS depressionSedatives causes more CNS depression

-- Antihypertensive drugs produce more posturalAntihypertensive drugs produce more posturalhypotensionhypotension


15/18

Drugs worsen existing clinical condition in renal failureDrugs worsen existing clinical condition in renal failure

Antimicrobials requiring dose reduction in renal failureAntimicrobials requiring dose reduction in renal failure

Even in mild failureEven in mild failure Only in severe failureOnly in severe failure

Aminoglycosides CotrimoxazoleAminoglycosides Cotrimoxazole

Ethambutol CefotaximeEthambutol Cefotaxime

Vancomycin Ciprofloxacin, NorfloxacinVancomycin Ciprofloxacin, Norfloxacin

Amphotreicin B MetronidazoleAmphotreicin B Metronidazole

AcyclovirAcyclovir

Diuretics :Diuretics :

Thiazide diuretics tends to reduce GFR, ineffective in renal failureThiazide diuretics tends to reduce GFR, ineffective in renal failureand can worsen uremiaand can worsen uremia

Potassium sparing diuretics are cotraindicated; can causePotassium sparing diuretics are cotraindicated; can causehyperkalemiahyperkalemia


16/18

ASSESSMENTASSESSMENT

Clinical features :Clinical features :

Oliguria, anuria, hematuriaOliguria, anuria, hematuria

FreqencyFreqency

Pedal swelling, facialPedal swelling, facialpuffiness, ascitespuffiness, ascites

Bone painBone pain

VomittingVomitting

Altered sensoriumAltered sensorium

H/O drug intakeH/O drug intake

CoCo--morbiditiesmorbidities

Pallor, BP, edema, volumePallor, BP, edema, volumestatus, flapping tremorstatus, flapping tremor

InvestigationsInvestigations

Routine tests :Routine tests :

Hb%, serum albumin,Hb%, serum albumin,

urea, creatinine,urea, creatinine,electrolyteselectrolytes

Urine R/E, M/E, C/SUrine R/E, M/E, C/S

Urinary ACRUrinary ACR

Imaging : XImaging : X--ray, USG, CTray, USG, CT

Clearance testsClearance tests Nuclear scanNuclear scan

Kidney biopsyKidney biopsy


17/18

Two formulas are widely used to estimate GFR:Two formulas are widely used to estimate GFR:

1) Cockcroft1) Cockcroft--Gault formulaGault formula

2) MDRD (Modification of Diet in Renal Disease)2) MDRD (Modification of Diet in Renal Disease)


18/18

drugs & kidney

Documents