drugs & kidney
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Dr. Sumit Kr. GhoshDr. Sumit Kr. GhoshAsst. ProfessorAsst. Professor
Department of MedicineDepartment of Medicine
Medical College & Hospital, KolkataMedical College & Hospital, Kolkata
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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
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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)
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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
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DRUGS & NORMAL KIDNEYDRUGS & NORMAL KIDNEY
Diuretics:Diuretics:
-- LoopLoop
-- ThiazideThiazide-- Aldosterone antagonistAldosterone antagonist
-- OsmoticOsmotic
Antidiuretics
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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
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Loop
Thiazide
Amiloride
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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