1.

Direct biochemical effect

Heavy metals: mercury, gold, iron, lead
Antimicrobial: aminoglycosides,
amphotericin, sulphonamides,
cephalosporins
X-ray contrast media
Analgesic: NSAID combinations
Solvents: carbon tetrachloride, ethylene
glycol

2. Indirect biochemical effect

Cytotoxic drugs and uricosurics
precipitated tubule
Calciferol
renal calcification
Diuretic and laxative abuse
tubule
damage
Anticoagulants
haemorrhage 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 syndrome
2. Tubule damage
Aspirin, cephalosporins, aminoglycosides
Heavy metal, radiographic contras media,
NSAID
3. Tubule obstruction
Methotrexate

1.

2.

3.

Vasculitis : sulphonamides, allopurinol,

isoniazid
Allergic interstitial nephritis : penicillins,
sulphonamides, thiazides, allopurinol,
phynitoin
Systemic lupus erythematosus :
hydralazine, procainamide

4. Acute renal failure : aminoglycoside,

cisplatin
5. Nephrotic syndrome : penicillinamine, gold,
captopril
6. Chronic renal failure : NSAID
7. Function impairment : lithium, loop
diuretics, acetazolamide

1.
2.
3.

Adjustment of the initial dose

Adjustment of the maintenance dose
Special cautions

Uraemia is accompanied by many

changes in homeostatic mechanism
Acidosis affect response to drugs by
altering tissue penetration of some
drugs
The kidneys have an increased
susceptibility to the nephrotoxic
effects of drugs

MODIFICATION of DOSE REGIMEN

1. Same dose can be given at
extended interval
2.

Reduced dose may be given at

usual interval

Type A (Augmented)
1.
Centrizonal necrosis: paracetamol,
carbon tetrachloride
2.
Hepatocelluler necrosis: salicylates
3.
Hepatic failure: tetracyclines
4.
Hepatitis with alcohol
5.
Interference with bilirubin metabolism:
oral contraceptive, rifampicin, fusidic
acid, cholecystographic media

Type B (Bizarre)
1.
Acute hepatocelluler necrosis : halothane,
phenytoin, carbamazepine, sodium
valproate, phenobarbitone, MAO ihibitor,
indomethacin, ibuprofen, isoniazed,
sulphonamides, nitrofurantoin,
methyldopa, hydralazine
2.
Cholestatic hepatitis: chlorpromazine,
chlorpropamide, tolbutamide,
glibenclamide, carbimazole,
erythromycine and gold

Type C (Continued)
1. Chronic acute hepatitis: methyldopa, INH,
nitrofurantoin
2. Hepatic fibrosis : alcohol, methotrexate,
amiodarone
Type D (Delayed effect)
1.
Benign liver tumors: anabolic steroid and
oral kontraceptives
2.
Hepatocelluler carcinoma
3.
Malignant liver tumor

1.
2.

3.

Drugs metabolising capacity is reduced

Liver cells that metabolise drugs are
bypassed
Liver disease cause hypoproteinaemia,
allowing more unbound and active drugs
to circulate

1.

Cellular response to drugs may alter

CNS sensitivity to opioids, sedatives,
antiepilepsy

2.

Fluid and electrolyte balance are altered

Sodium retention (induced by NSAID,
corticosteroid)
Ascites and oedema