Drug induced nephrotoxicity

Drug induced nephrotoxicity

1. Presentation by SAQIB ZAMAN 4 th prof clinical clerkship

2. Drug induced Nephrotoxicity

3. What is Nephrotoxicity : Nephrotoxicity  is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on renal function. Toxicity produced due to certain drugs is called Drug induced nephrotoxicity .

4. Drugs are a common source of acute kidney injury .   drugs  shown to cause nephrotoxicity  exert their toxic effects by one or more common pathogenic mechanisms. Drug-induced nephrotoxicity  tends to be more common among certain patients and in specific clinical situations.

5. Risk Factors Patient related factors: Age, sex, race Pre-existent renal disease Specific disease (diabetes mellitus, multiple myeloma, proteinuric patients) Sodium-retaining states (cirrhosis, heart failure, nephrosis ) Dehydration and volume depletion

6. Risk factors Acidosis, potassium and magnesium depletion Hyperuricemia , Hyperuricosuria Sepsis shock Renal transplantation

7. Risk factors Drug-related factors : Inherent nephrotoxic potential Dose Duration, frequency and form of administration Repeated exposure

8. Risk factors Drug interactions: Combined or closely associated use of diagnostic or therapeutic agents with added or synergistic nephrotoxic potential (e.g. Radiocontrast agents, aminoglycosides , NSAIDs, cisplatin,ACEI )

9. Clinical Presentation General • The most common manifestation is a decline in GF leading to a rise in Scr and BUN. Symptom • Malaise, anorexia, vomiting, shortness of breath, or edema.R leading to a rise in Scr and BUN.

10. Signs • Decreased urine output may be an early sign of toxicity, particularly with radiographic contrast media, NSAIDs, and ACEIs, with progression to volume overload and hypertension.

11. Pathogenic mechanism Most drugs found to cause nephrotoxicity exert toxic effects by one or more common pathogenic mechanisms. These include altered intraglomerular hemodynamics , tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis , and thrombotic microangiopathy. 7   Knowledge of offending drugs and their particular pathogenic mechanisms of renal injury is critical to recognizing and preventing drug-induced renal impairment

12. Pathogenic mechanisms DRUGS CLASS Analgesics Acetaminophen , aspirin Nonsteroidal anti-inflammatory drugs MECHANISMS Chronic interstitial nephritis Acute interstitial nephritis, altered intraglomerular hemodynamics , chronic interstitial nephritis, glomerulonephritis .

13. Antidepressants/mood stabilizers Amitriptyline , doxepin , fluoxetine . Lithium Rhabdomyolysis Chronic interstitial nephritis, glomerulonephritis , rhabdomyolysis

14. Antihistamines: Diphenhydramine , doxylamine Antimicrobials: Acyclovir Aminoglycosides Amphotericin B Rhabdomyolysis Acute interstitial nephritis, crystal nephropathy. Tubular cell toxicity. Tubular cell toxicity

15. Cardiovascular agents Angiotensin -converting enzyme inhibitors, angiotensin receptor blockers Clopidogrel Statins Altered intraglomerular hemodynamics . Thrombotic microangiopathy . Rhabdomyolysis .

16. Drugs of abuse Cocaine , heroin, ketamine , methadone, methamphetamine Proton pump inhibitors Lansoprazole , omeprazole , pantoprazole   Rhabdomyolysis . Acute interstitial nephritis

17. TUBULAR CELL TOXICITY Renal tubular cells, in particular proximal tubule cells, are vulnerable to the toxic effects of drugs because their role in concentrating and reabsorbing glomerular filtrate exposes them to high levels of circulating toxins. Drugs that cause tubular cell toxicity do so by impairing mitochondrial function, interfering with tubular transport, increasing oxidative stress, or forming free radicals. Drugs associated with this pathogenic mechanism of injury include aminoglycosides , amphotericin B, antiretrovirals etc

18. Rhabdomyolysis Rhabdomyolysis is a syndrome in which skeletal muscle injury leads to lysis of the myocyte , releasing intracellular contents including myoglobin and creatine kinase into the plasma. Myoglobin induces renal injury secondary to direct toxicity, tubular obstruction, and alterations in GFR

19. Drugs may induce rhabdomyolysis directly secondary to a toxic effect on myocyte function, or indirectly by predisposing the myocyte to injury.  Clinical manifestations of rhabdomyolysis include weakness, myalgia , and tea-colored urine. Statins are the most recognizable agents associated with rhabdomyolysis .   Also cocaine , heroin, ketamine , methadone, and methamphetamine, have been reported to cause rhabdomyolysiS

20. General Measures to Prevent Drug-Induced Nephrotoxicity Adjust medication dosages using the Cockcroft- Gault formula (in adults) or Schwartz formula (in children). Avoid nephrotoxic combination. Correct risk factors for nephrotoxicity before initiation of drug therapy. Ensure adequate hydration before and during therapy with potential nephrotoxins . Use equally effective non- nephrotoxic drugs whenever possible.

21. References: https://www.aafp.org.com Hand book of clinical pharmacy