DRUG INDUCED KIDNEY DISEASE
DRUG INDUCED KIDNEY DISEASE
DRUG INDUCED KIDNEY DISEASE
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<strong>DRUG</strong> <strong>INDUCED</strong><br />
CHAPTER: 3<br />
<strong>KIDNEY</strong> <strong>DISEASE</strong><br />
BY<br />
Mrs. K.SHAILAJA., M. PHARM.,<br />
LECTURER<br />
DEPT OF PHARMACY PRACTICE,<br />
SRM COLLEGE OF PHARMACY
INTRODUCTION<br />
• Drug induced kidney disease or nephrotoxicity is a<br />
relatively common complication of several diagnostic<br />
and therapeutic agents.<br />
• TYPES :<br />
• 1. HAEMODYNAMIC CHANGES :<br />
• It leads to ARF , ATN ,Nephrotoxicity<br />
• ACE inhibitors<br />
• Angiotensin –II antagonists<br />
• NSAIDS
2INTRINSIC NEPHROTOXICITY <br />
TUCAE TUBULAR NECROSIS <br />
• Aminoglycosides<br />
• Cytotoxic drugs<br />
• Radiocontrast<br />
• ACUTE INTERSTITIAL NEPHRITIS<br />
• NSAID<br />
• Antibiotics<br />
• Diuretics<br />
• Proton pump inhibitors
• GLOMERULOPATHY:<br />
• NSAIDS<br />
• Gold<br />
• Pencillamide<br />
• OBSTRUCTIVE NEPHROPATHY:<br />
• Crystal uria<br />
• Cytotoxic drugs<br />
• Ciprofloxacin<br />
• sulphonamides
RETROPERITONEAL FIBROSIS:<br />
• Methysergide<br />
• Bromocriptine<br />
• methotrauxate
NSAID induced haemodynamic<br />
mechanisms:<br />
• phospholipid<br />
phospholipase A<br />
•<br />
• Arachidonic acid<br />
•<br />
5‐lipoxygenase cyclooxygenase‐I<br />
• 5HPETE<br />
• PGG II<br />
• 5HETE PGH synthesis<br />
• Leukotrienes PGH2 PGE2<br />
• LTA4,LTB4,LTC4 PGP2<br />
• LT receptor thromboxane synthase<br />
• thromboxane
• TREATMENT FOR HAEMODYNAMIC<br />
ARF:<br />
• With drawl of drug<br />
• Correct the renal blood flow<br />
• Treat the hyperkalemia<br />
• Serum potassium concentration should be carefully<br />
monitered
INTRINSIC NEPHROTOXICITY :<br />
• ACUTE INTERSTITIAL NEPHRITIS:<br />
• ETIOLOGY:<br />
• Idiosyncratic allergic drug interactions<br />
• Long term exposure of a drug<br />
• Because of hospitalization for longer period<br />
• This type of reactions occur after 2weeks of exposure<br />
• CLINICAL FEATURES:<br />
• Pyrexia<br />
• Rash<br />
• arthralgia
• IgE concentration in serum will be increased<br />
• Urine analysis – microscopical exam‐ shows the<br />
presence of leukocytes and neutrophils<br />
• Delayed renaluptake of gallium 67 on scintigraphy<br />
• Renal biopsy it shows inflammatory infilterate with<br />
variable number of eosinophils,lymphocytes,plasma cells<br />
• TREATMENT:<br />
• No need of renal replacement therapy and dialysis<br />
• Withdrawl of drug<br />
• Corticosteroids are helpful
<strong>DRUG</strong>S:<br />
• Beta‐lactam antibiotics:<br />
• Pencillin and cephalosporins<br />
• Other antibiotics:<br />
• Ciprofloxacin<br />
• Rifampicin<br />
• Sulphonamides<br />
• NSAIDS:<br />
• Ibuprofen<br />
• Selective COX II inhibitors‐ celecoxib
• DIURETICS:<br />
• Furosemide<br />
• Thiazide<br />
• PPI<br />
• Omeprazole<br />
• Lansoprazole<br />
• OTHERS:<br />
• Amodipine<br />
• Allopurinol, rifampicin<br />
• Dilthizem , phenytoin
Acute tubular necrosis :<br />
• ANTIBIOTICS:<br />
• Gentamycin<br />
• Vancomycin<br />
• ANTI‐VIRAL:<br />
• Cidofovir<br />
• Adefovir<br />
• Tenofovir<br />
• CYTOTOXIC <strong>DRUG</strong>S:<br />
• Cisplantin,cyclosporin,mitomycin
• Three phases:<br />
• Intiation phase<br />
• Maintenance phase<br />
• Recovery phase<br />
•<br />
• HYPOTENSION,<br />
VASOCONSTRICTORS<br />
• INCREASED NITRIC ACID SYNTHASE<br />
• Increased NO, cytokines( IL‐1 TNF‐@,free radicals)
Initiation phase:<br />
• Ischemia/nephrotoxins<br />
• Injury tubular epithelial cells<br />
• Cell death/detachment of basement membrane<br />
• Tubular necrosis<br />
Decreased blood volume/hypoperfusion<br />
• Decreased in GFR, increased serum creatinine,BUN concentration
MAINTENANCE PHASE :<br />
• Tubular necrosis<br />
• Tubular obstruction , increase in tubular<br />
permeability<br />
• Sustained reduction in GFR<br />
• azotemia,fluid retention,electrolyte<br />
imbalance,metabolic acidosis
RECOVERY PHASE:<br />
• RENAL FUNCTION<br />
Repair and regeneration of renal tissues<br />
Stimulation of growth factors<br />
Repair and promoting the proliferation of renal tubular cells<br />
Tubular function restored<br />
Increase in renal volume<br />
Gradual decrease in serum creatinine<br />
and urea level
PREVENTION:<br />
Nephrotic agents should be avoided in :<br />
Geriatric patients<br />
Heart failure<br />
Liver disease<br />
Existing renal disease<br />
Renal artery stenosis<br />
Diabetes mellitus<br />
TREATMENT<br />
Withdrawal of the drug that is responsible for ATN<br />
Monitor the fluid balance<br />
Hydration status and electrolyte
• Renal replacement therapy In emergency<br />
• IV dopamine 1‐3microgram /kg/minute is administered<br />
moa is selective vasodilation of renal disease<br />
• GLOMERULOPATHY:<br />
• NSAIDS cause glomerulopathy<br />
• Immune complex reactions<br />
• Immune complex gets deposited at the subepithelial<br />
space<br />
• Antigen is PLA2R binds to A2 receptor<br />
• OBSTRUCTIVE NEPHROPATHY:<br />
• Due to obstruction<br />
• Crystal and stone formation within uretic lumen
URATE NEPHROPATHY:<br />
• Accumulation of uric acid<br />
• Extensive cell lysis and purine catabolism results<br />
in rapid formation of uric acid
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