DRUG INDUCED KIDNEY DISEASE [PDF]

CHAPTER: 3

DRUG INDUCED  KIDNEY DISEASE BY Mrs. K.SHAILAJA., M. PHARM., LECTURER DEPT OF PHARMACY PRACTICE, SRM COLLEGE OF PHARMACY

INTRODUCTION

ƒ Drug induced kidney disease  or nephrotoxicity is a  relatively common complication of several diagnostic  and therapeutic agents.

ƒ TYPES : ƒ 1. HAEMODYNAMIC CHANGES : ƒ It leads to  ARF , ATN ,Nephrotoxicity ƒ ACE inhibitors ƒ Angiotensin –II antagonists ƒ NSAIDS

2 INTRINSIC NEPHROTXICITY ACUTE TUBLAR NECROSIS ƒ Aminoglycosides ƒ Cytotoxic drugs  ƒ Radiocontrast

ƒ ACUTE INTERSTITIAL NEPHRITIS ƒ ƒ ƒ ƒ

NSAID Antibiotics Diuretics Proton pump inhibitors

ƒ GLOMERULOPATHY: ƒ NSAIDS ƒ Gold ƒ Pencillamide

ƒ OBSTRUCTIVE  NEPHROPATHY: ƒ Crystal uria ƒ Cytotoxic drugs ƒ Ciprofloxacin ƒ sulphonamides

RETROPERITONEAL  FIBROSIS: ƒ Methysergide ƒ Bromocriptine ƒ methotrauxate

NSAID induced haemodynamic  mechanisms: ƒ

phospholipid  phospholipase A

ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ

Arachidonic acid 5‐lipoxygenase                                                              cyclooxygenase‐I 5HPETE                                                              PGG II 5HETE                                                                  PGH synthesis Leukotrienes PGH2                              PGE2 LTA4,LTB4,LTC4                                                 PGP2 LT receptor                   thromboxane synthase thromboxane

ƒ TREATMENT  FOR  HAEMODYNAMIC   

ARF: ƒ With drawl of drug ƒ Correct the renal  blood flow ƒ Treat the hyperkalemia ƒ Serum potassium concentration should  be carefully 

monitered

INTRINSIC NEPHROTOXICITY : ƒ ACUTE  INTERSTITIAL  NEPHRITIS: ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ

ETIOLOGY: Idiosyncratic allergic drug interactions Long term  exposure of a drug Because of hospitalization for longer period This type of reactions occur after 2weeks of exposure CLINICAL FEATURES: Pyrexia Rash arthralgia

ƒ IgE concentration in serum will be increased ƒ Urine analysis – microscopical exam‐ shows the  ƒ ƒ ƒ ƒ ƒ ƒ

presence of leukocytes and neutrophils Delayed renaluptake of gallium 67 on scintigraphy Renal biopsy it shows inflammatory infilterate with  variable number of eosinophils,lymphocytes,plasma cells TREATMENT: No need of renal replacement therapy  and dialysis Withdrawl of drug Corticosteroids are helpful 

DRUGS: ƒ Beta‐lactam antibiotics: ƒ Pencillin and cephalosporins

ƒ Other antibiotics: ƒ Ciprofloxacin ƒ Rifampicin ƒ Sulphonamides

ƒ NSAIDS: ƒ Ibuprofen ƒ Selective COX II inhibitors‐ celecoxib

ƒ DIURETICS: ƒ Furosemide ƒ Thiazide

ƒ PPI  ƒ Omeprazole ƒ Lansoprazole

ƒ OTHERS: ƒ Amodipine ƒ Allopurinol,   rifampicin ƒ Dilthizem , phenytoin

Acute tubular necrosis : ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ

ANTIBIOTICS: Gentamycin Vancomycin ANTI‐VIRAL: Cidofovir Adefovir Tenofovir CYTOTOXIC DRUGS: Cisplantin,cyclosporin,mitomycin

ƒ ƒ ƒ ƒ ƒ ƒ

Three phases: Intiation phase Maintenance phase Recovery phase HYPOTENSION,  VASOCONSTRICTORS

ƒ INCREASED NITRIC ACID SYNTHASE ƒ Increased  NO, cytokines( IL‐1 TNF‐@,free radicals)

Initiation phase: ƒ

Ischemia/nephrotoxins

ƒ

Injury tubular epithelial  cells

ƒ

Cell death/detachment   of    basement  membrane

ƒ

Tubular necrosis

Decreased  blood volume/hypoperfusion ƒ

Decreased in GFR, increased serum creatinine,BUN concentration

MAINTENANCE PHASE : ƒ

Tubular necrosis

ƒ Tubular obstruction ,  increase in tubular 

permeability ƒ Sustained reduction in GFR 

ƒ azotemia,fluid retention,electrolyte

imbalance,metabolic acidosis

RECOVERY PHASE: ƒ

RENAL FUNCTION

Repair and regeneration of renal  tissues Stimulation      of        growth factors Repair and promoting       the         proliferation        of     renal tubular   cells Tubular function restored Increase in renal volume Gradual decrease in serum creatinine and urea level

PREVENTION: Nephrotic agents should be avoided in : Geriatric patients Heart failure Liver disease Existing renal disease Renal artery stenosis Diabetes mellitus TREATMENT Withdrawal of the drug that is responsible for ATN Monitor the fluid balance Hydration status and electrolyte

ƒ Renal   replacement    therapy  In  emergency ƒ IV  dopamine 1‐3microgram /kg/minute is administered   

moa  is selective vasodilation of renal disease ƒ GLOMERULOPATHY: ƒ NSAIDS cause glomerulopathy ƒ Immune complex reactions ƒ Immune complex gets deposited at the subepithelial ƒ ƒ ƒ ƒ

space Antigen is PLA2R binds to A2 receptor OBSTRUCTIVE NEPHROPATHY: Due to obstruction  Crystal and stone formation within uretic lumen

URATE  NEPHROPATHY: ƒ Accumulation of uric acid ƒ Extensive cell lysis and purine catabolism results 

in rapid formation of uric acid