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THE EFFECTS OF DRUGS ON THE KIDNEY

I. RENAL HEMODYNAMIC CHANGES 1. NSAIDS - Indomethacin - Naproxen = Naprosyn - Mefenemic Acid Decrease GFR They inhibit the synthesis of prostaglandins since they are prostaglandine syntetase inhibitors and prostaglandins are important in maintaining vasodilation and promotion of renal blood flow
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2. ANGIOTENSIN CONVERTING ENZYM ( = ACE ) INHIBITORS

- Captopril - Enalapril Can cause renal failure they antagonise the angiotensin II receptors at the efferent arterioles of glomeruli and thereby decrease intraglomerular BP resulting in lowered GFR
3. Cyclosporin A

Can cause severe tubulo intertitial injury as well as inhibition of prostaglandin synthesis resulting in renal failure Cyclosporin A also cause increased platelet aggregation and predisposes to thrombosis of renal blood vessels
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II. IMMUNOLOGICALLY MEDIATED DAMAGE

1. Sulphonamide Bactrim Allopurinol Methicillin Ampicillin

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3.

Cause an acute allergic intertitial nephritis associated with steven johnsons syndrome Penicillamine produce a membranous glomerulonephritis resulting in the nephrotic syndrome. Rifampicin can give rise to an immune complex glomerulonephritis Methicillin can cause rapidly progressiv glomerulonephritis due to formation of anti glomerular besement membrane antibodies ( anti GBM Antibodies )
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III. DIRECT TUBULAR TOXICITY

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Lithium Carbonate Is toxic to the distal tubuler and causes neprogenic diabetes insipidius Amphotericin B produces tubular damage with renal impairment type I RTA Outdated tetracyclines cause fancony is syndrome type II RTA tetracyclines too causes a hypercatabolic state marked elevation of blood urea in patients with renal impairment Analgesics like aspirin even paracetamol in high dose and NSAIDS Cause papillary necrosis of the kidneys (analgesic Nephropathy ). Aminoglycosides damage predominanatly the proximal tubules Characteristically produce non olyguric acut renal failure.

More commonly in the eldery espacially when they are dehydrated or given diuretics Combination with cephaloridine further aggrevate nephrotoxicity The second and third generation cephalosporin do not have a synergistic neprotoxic effect with aminoglycosides

IV. BLOCKAGE OF RENAL TUBULES

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4.

Sulphonamides, cause crystaluria because of poor solubility especially in an acidic urine Methotrexate, cause acute tubuler necrosis due to its precipitation in the renal tubuler Methoxy flurane, cause oxaluria with intratubular precipitation of calcium oxalate crystals giving rise to renal failure Triamterent, causes crystals and casts to form in tubules, giving rise to triamterenes stones.
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V.

INJURY RELATED TO CHANGE IN ELECTRICTROLYTE

1.Diuretics cause hypokalemia inducing vacuolar degeneration of the tubules with nephrogenic diabetes insipidus. 2.Vitamin D therapy can induce hypercalsemia presdisposing to internal calcification and tubular damage with renal impairmenT.

PRACTICE POINTS
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In Any patient with renal impairment it is always useful to take drug history. In Any patient with rash and renal impairment, think of acute allergic intertitiel nephritis. (check eosinophils in urine). Remember aminoglycosides as a very common cause of renal impairment when dealing with a patient who has sepsis and renal failure. Withdrawl of the offending agent, eg ACE inhibitor will result improvement of renal function. Sometime renal biopsy may have to do.
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