Clinical Pharmacology in Renal Disease

Question 1

What are the principles of drug therapy in the presence of renal insufficiency?

Answer 1

1) Renal function can have a dramatic effect on pharmacokinetics or pharmacodynamics
2) Drugs with narrow therapeutic indexes are especially dangerous in patients with renal disease
3) All drugs and their metabolites are filtered at the glomerulus

Question 2

What are the pharmacokinetic and pharmacodynamic effects of impaired renal function on drug clearance?

Answer 2

Pharmacokinetic effects:

• Reduction in GFR reduces clearance of drugs by the kidney, resulting in accumulation (must reduce dosage, increase dose interval)
• Protein binding is reduced

Pharmacodynamic effects:

• Renal disease alters the actions of drugs in tissues
• BBB becomes more permeable
• Circulating volume may be reduced, making the patient more sensitive to ACEI’s

Question 3

How can drug-induced nephrotoxicity be limited?

Answer 3

• Understanding which drugs can be used when patients have low GFR and which drugs have a low therapeutic index
• Reducing maintenance dose and loading dose
• Increasing the dosing interval
• Monitor renal function and blood pressure

Question 4

Give some examples of drug-induced renal disease

Answer 4

Drug induced renal toxicity can cause 4 major syndromes:

1) Acute renal failure (pre, renal or post-renal) - Acute tubular necrosis caused by aminoglycosides
2) Nephrotic syndrome - NSAID’s
3) Renal tubular dysfunction with potassium wasting
4) Chronic renal failure