Nephrotoxic drugs

Question 1

What is important to note when prescribing in patients with reduced renal function?

Answer 1

• Reduced renal function can result in reduced drug excretion resulting in toxicity
• Drugs can be nephrotoxic and cause further damage

Question 2

What are the drugs most commonly associated with nephrotoxicity?

Answer 2

• Aminoglycosides (gentamycin, streptomycin)
• NSAIDs
• Contrast agents
• ARBs/ ACEis

Question 3

Which drugs cause pre-renal toxicity?

Answer 3

ACEi + ARBs - cause vasoconstriction and reduce renal blood flow

Cyclosporin + tacrolimus - calcineurin inhibitors, blocks T-cell activation and also reduce blood flow to the kidney (the achilles heal of transplantation)

Question 4

Which drugs cause post-renal toxicity?

Answer 4

All cause crystal formation and blockage:

• Acyclovir
• Methotrexate
• Sulfonamides

Question 5

What is very important to check before prescribing an NSAID?

Answer 5

The hydration status of the patient - if a patient is dehydrated, a low dose of a NSAID can be lethal

Question 6

Which drugs cause direct renal toxicity?

Answer 6

Acute tubular necrosis:

• Aminoglycosides
• Amphotericin B
• Cisplatin
• Contrast

Acute interstitial nephritis:

• Thiazides
• Penicillin and B lactams
• Sulfonamides

Question 7

Which drugs cause tubular toxicity?

Answer 7

PCT: aminoglycosides, amphotericin B, cisplatin, contrast, mannitol

DCT: NSAIDs, ACEi, ciclosporin, cyclophosphamide, amphotericin B

Tubular obstruction: sulphonamides, methotrexate, aciclovir

Question 8

Which ways are drugs excreted?

Answer 8

1. Heptobiliary system e.g. rifampacin
2. Kidneys (most drugs are excreted this way)

Question 9

Define drug clearance

Answer 9

= Concentration of drug in the urine (Cu) x the rate at which urine is produced (Vu) / concentration of the drug in plasma (Cp)

* this calculates how much of the drug is being cleared by the body at a given time

e.g. 500ml of plasma is being cleared of the drug per minute

Question 10

What question does calculating drug clearance allow us to answer?

Answer 10

If there is x amount of drug in the plasma, how quickly can I get rid of it?

Question 11

What factors affect drug clearance?

Answer 11

• Dose of the drug given (Cp)
• GFR (as this affects Vu)
• Some drugs have to be metabolised by enzymes before they can be excreted, if a high dose is given the enzymes become saturated and the drug cannot be metabolised. This means the rate of excretion is not related to increasing the dose of the drug = zero order kinetics e.g. ethanol

Question 12

Which drugs are not removed by haemodialysis?

Answer 12

• Digoxin
• Tricyclic antidepressants
• Phenytoin
• Benzos
• B-blockers
• Oral hypoglycaemic agents

Question 13

What affect can muscle breakdown have on the kidneys?

Answer 13

Rhabdomyolysis leads to myoglobin release, myoglobin is nephrotoxic