DRUG INDUCED CHAPTER: 3 KIDNEY DISEASE BY Mrs. K.SHAILAJA., M. PHARM., LECTURER DEPT OF PHARMACY PRACTICE, SRM COLLEGE OF PHARMACY
INTRODUCTION Drug induced kidney disease or nephrotoxicity is a relatively common complication of several diagnostic and therapeutic agents. TYPES : 1. HAEMODYNAMIC CHANGES : It leads to ARF, ATN,Nephrotoxicity ACE inhibitors Angiotensin II antagonists NSAIDS
2INTRINSIC NEPHROTOXICITY TUCAE TUBULAR NECROSIS Aminoglycosides Cytotoxic drugs Radiocontrast ACUTE INTERSTITIAL NEPHRITIS NSAID Antibiotics Diuretics Proton pump inhibitors
GLOMERULOPATHY: NSAIDS Gold Pencillamide OBSTRUCTIVE NEPHROPATHY: Crystal uria Cytotoxic drugs Ciprofloxacin sulphonamides
RETROPERITONEAL FIBROSIS: Methysergide Bromocriptine methotrauxate
NSAID induced haemodynamic mechanisms: phospholipid phospholipase A Arachidonic acid 5 lipoxygenase cyclooxygenase I 5HPETE PGG II 5HETE PGH synthesis Leukotrienes PGH2 PGE2 LTA4,LTB4,LTC4 PGP2 LT receptor thromboxane synthase thromboxane
TREATMENT FOR HAEMODYNAMIC ARF: With drawl of drug Correct the renal blood flow Treat the hyperkalemia Serum potassium concentration should be carefully monitered
INTRINSIC NEPHROTOXICITY : ACUTE INTERSTITIAL NEPHRITIS: 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
IgE concentration in serum will be increased Urine analysis microscopical exam shows the 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: Beta lactam antibiotics: Pencillin and cephalosporins Other antibiotics: Ciprofloxacin Rifampicin Sulphonamides NSAIDS: Ibuprofen Selective COX II inhibitors celecoxib
DIURETICS: Furosemide Thiazide PPI Omeprazole Lansoprazole OTHERS: Amodipine Allopurinol, rifampicin Dilthizem, phenytoin
Acute tubular necrosis : ANTIBIOTICS: Gentamycin Vancomycin ANTI VIRAL: Cidofovir Adefovir Tenofovir CYTOTOXIC DRUGS: Cisplantin,cyclosporin,mitomycin
Three phases: Intiation phase Maintenance phase Recovery phase HYPOTENSION, VASOCONSTRICTORS INCREASED NITRIC ACID SYNTHASE Increased NO, cytokines( IL 1 TNF @,free radicals)
Initiation phase: Ischemia/nephrotoxins Injury tubular epithelial cells Cell death/detachment of basement membrane Tubular necrosis Decreased blood volume/hypoperfusion Decreased in GFR, increased serum creatinine,bun concentration
MAINTENANCE PHASE : Tubular necrosis Tubular obstruction, increase in tubular permeability Sustained reduction in GFR azotemia,fluid retention,electrolyte imbalance,metabolic acidosis
RECOVERY PHASE: 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
Renal replacement therapy In emergency IV dopamine 1 3microgram /kg/minute is administered moa is selective vasodilation of renal disease GLOMERULOPATHY: NSAIDS cause glomerulopathy Immune complex reactions Immune complex gets deposited at the subepithelial space Antigen is PLA2R binds to A2 receptor OBSTRUCTIVE NEPHROPATHY: Due to obstruction Crystal and stone formation within uretic lumen
URATE NEPHROPATHY: Accumulation of uric acid Extensive cell lysis and purine catabolism results in rapid formation of uric acid