Nephrotoxic drugs

NEphrotoxic Drugs for BSc Nursing.

1. Nephrotoxic Drugs For BSc Nursing Dr. Pravin Prasad 1 st Yr Resident, MD Clinical Pharmacology Maharajgunj Medical Campus 5 th August , 2015 (20 th Shrawan , 2072 )

2. Introduction Is it necessary?? Renal damage causes significant morbidity and mortality Acute Kidney Injury Acute Tubular Necrosis Chronic Kidney Disease Inflammatory Disorders Increasing healthcare expense Both to individual and nation Renal Damage due to drugs is preventable

3. Nephrotoxicity and Agents responsible Nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. Nephrotoxins  are chemicals displaying nephrotoxicity. May lead to: More side effects Increased nephrotoxicity Change in the drug metabolism

4. Screening for Acute Kidney Injury

5. Common Drugs leading to Nephrotoxicity Antibiotics: Aminoglycoside, Vancomycin Anti Fungals Amphotericin B Immunomodulators Calcineurin inhibitors Chemotherapeutic agents Cyclosporin , Tacrolimus Antivirals Acyclovir Anti Hypertensives ACE inhibitors, ARBs Diuretics β -blockers NSAIDs /cox-2 inhibitors Cocaine Ethylene glycol Occupational toxins (heavy metals, organic solvents) Herbal remedies

6. Mechanisms of Nephrotoxicity OUTER MEDULLA INNER MEDULLA CORTEX ACUTE PRE-RENAL FAILURE AMPHOTERICIN, ANTIHYPERTENSIVES, DIURETICS, DOXORUBICIN, NSAIDS, CYCLOSPORIN-A NEPHROTIC SYNDROME NSAIDS, PENICILLAMINE CAPTOPRIL HEROIN/COCAINE ATN(P): ACUTE TUBULAR NECROSIS AMINOGLYCOSIDES, ANTINEOPLASTICS, GLYCOLS, ATN(D): ACUTE TUBULAR NECROSIS AMPHOTERICIN, CISPLATIN, GLYCOLS CHRONIC INTERSTITIAL NEPHRITIS ANALGESIC COMBINATIONS, CHINESE HERBS, CYCLOSPORINE, METALS (PB, Cd , Li, Ge ), METHYL-CCNU ACUTE INTERSTITIAL NEPHRITIS ALLOPURINOL, RIFAMPIN, VANCOMYCIN, NSAIDS OBSTRUCTION ACYCLOVIR, ANTICHOLINERGICS, BROMOCRIPTINE, ERGOT ALKALOIDS, FLUOROQUINOLONE, MTX VASCULITIS AMPHETAMINES, NSAIDS, PENICILLINS,SULFONAMIDES

7. Mechanism of Toxicity Cardiovascular: General: diuretics,  β- blockers, vasodilator agents Local: ACE inhibitors, cyclosporine, tacrolimus. Direct Tubular Effects: PCT: Aminoglycoside antibiotics ,  amphotericin B, cisplatin, radiocontrast media, immunoglobulins, mannitol Distal tubule: NSAIDs (e.g. aspirin, ibuprofen, diclofenac), ACE inhibitors,  cyclosporin , lithium salts, cyclophosphamide, amphotericin B Tubular obstruction: sulphonamides, methotrexate,  aciclovir , diethylene glycol, triamterene . Acute Interstitial Nephritis: Antibiotic ( β –lactams) Vancomycin , rifampicin, sulphonamides, ciprofloxacin, NSAIDs, ranitidine,  cimetidine,  furosemide, thiazides,  phenytoin Others: Crystal nephropathy Thrombotic microangiopathy Rhabdomylosis 

8. Renal Biomarkers

9. Renal Biomarkers Traditional tools: Diagnose AKI: Serum Creatinine Determine etiology: Clinical history, physical examination, renal ultrasound, fractional excretion of sodium [ FeNa ], fractional excretion of urea, blood urea nitrogen [BUN], and urine microscopy) New Biomarkers: under research Cystatin C Marker Neutrophil Gelatinase- Associated Lipocaline (NAGL)( Lipocalin-2 or siderocalin ) Kidney injury molecule (KIM-1)

10. Dose Adjustment of Drugs Cockcroft and Gault Estimated Creatinine Clearance ( eCrCl ) = ([140 – age (years)] × ideal body weight [kg]) ÷ (serum creatinine [ mg/ dL ] × 72) Male: eCrCl x 1 Female : male eCrCl × 0.85 To adjust drug dosing for renal function in adults

11. Renal Protective Strategies: Example Exposure Strategy Aminoglycoside antibiotics Once – daily dosing; Monitoring of drug levels ; Avoiding in CKD and pts at risks; Maintain trough levels < 1mcg /ml. Amphotericin B Use lipid formulation; Saline hydration pre and post administration; Avoid high or rapid dose or prolonged duration Ethylene glycol ingestion Ethanol/ fomepizole ; hemodialysis Methotrexate IV hydration/urine alkalinization Acyclovir IV hydration Calcineurin inhibitors Monitoring drug levels; Lowering the doses; ± CCB Acetaminophen , Aspirin, NSAIDs Avoid long-term use; More than one drug; Avoid in old age; Monitor cumulative consumptions and avoid it; Avoid combination wit RAS blockers RAS inhibitors Fluid correction before drugs initiation; Monitoring s. creatinine Acyclovir ; Methotrexate Sulfa ATB; Triamterene Discontinue or reduce dose; Hydration; Oral route Establish high urine flow