Direct biochemical effectHeavy metals: mercury, gold, iron, leadAntimicrobial: aminoglycosides, amphotericin, sulphonamides, cephalosporins X-ray contrast mediaAnalgesic: NSAID combinationsSolvents: carbon tetrachloride, ethylene glycol
2. Indirect biochemical effect Cytotoxic drugs and uricosurics precipitated tubule Calciferolrenal calcification Diuretic and laxative abusetubule damage Anticoagulantshaemorrhage in to the kidney
3. Immunological effect Drugs : phenytoin, gold, penicilline, sulphonamides, hydralazine, isoniazid, rifampicine, procainamide, penicillamine, probenecid Injuries : arteritis, glomerulitis, interstitial nepritis, systemic lupus erythematosus
1. Glomerular damage Damage from circulating immune complexes: Glomerulonephritis, protienuria and nephrotic syndrome2. Tubule damage Aspirin, cephalosporins, aminoglycosides Heavy metal, radiographic contras media, NSAID3. Tubule obstruction Methotrexate
Vasculitis : sulphonamides, allopurinol, isoniazidAllergic interstitial nephritis : penicillins, sulphonamides, thiazides, allopurinol, phynitoinSystemic lupus erythematosus : hydralazine, procainamide
4. Acute renal failure : aminoglycoside, cisplatin5. Nephrotic syndrome : penicillinamine, gold, captopril6. Chronic renal failure : NSAID7. Function impairment : lithium, loop diuretics, acetazolamide
Adjustment of the initial doseAdjustment of the maintenance doseSpecial cautions
Uraemia is accompanied by many changes in homeostatic mechanismAcidosis affect response to drugs by altering tissue penetration of some drugsThe kidneys have an increased susceptibility to the nephrotoxic effects of drugs
MODIFICATION of DOSE REGIMENSame dose can be given at extended interval
Reduced dose may be given at usual interval
Type A (Augmented)Centrizonal necrosis: paracetamol, carbon tetrachlorideHepatocelluler necrosis: salicylates Hepatic failure: tetracyclinesHepatitis with alcoholInterference with bilirubin metabolism: oral contraceptive, rifampicin, fusidic acid, cholecystographic media
Type B (Bizarre)Acute hepatocelluler necrosis : halothane, phenytoin, carbamazepine, sodium valproate, phenobarbitone, MAO ihibitor, indomethacin, ibuprofen, isoniazed, sulphonamides, nitrofurantoin, methyldopa, hydralazineCholestatic hepatitis: chlorpromazine, chlorpropamide, tolbutamide, glibenclamide, carbimazole, erythromycine and gold
Type C (Continued)1. Chronic acute hepatitis: methyldopa, INH, nitrofurantoin2. Hepatic fibrosis : alcohol, methotrexate, amiodaroneType D (Delayed effect)Benign liver tumors: anabolic steroid and oral kontraceptivesHepatocelluler carcinomaMalignant liver tumor
Drugs metabolising capacity is reducedLiver cells that metabolise drugs are bypassedLiver disease cause hypoproteinaemia, allowing more unbound and active drugs to circulate
Cellular response to drugs may alter CNS sensitivity to opioids, sedatives, antiepilepsyFluid and electrolyte balance are alteredSodium retention (induced by NSAID, corticosteroid)Ascites and oedema
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