Clinical Pharmacology

Question 1

Describe 2 mechanisms in which renal disease effects drug action [5]

Answer 1

Pharmacokinetic:

• Less clearance –> Increased Half life –> Raised plasma levels of drug
• Reduces protein binding so higher active plasma levels

Pharmacodynamic:

• BBB more permeable so brain more sensitive to sedatives/opiates
• Low circulatory volume –> danger with anti-hypertensives
• Increased bleeding tendency due to loss of anti-thrombin. Beware NSAIDs & warfarin

Question 2

How do we take renal disease into account when prescribing? [5]

Answer 2

• Use drugs that are safe at a low GFR, avoid nephrotoxic
• Avoid drugs with a narrow therapeutic index
• Try to use drugs metabolised outside the kidneys (mainly liver) to non-toxic metabolites
• Reduce doses and increase dose intervals
• Therapeutic Drug Monitoring (TDM), monitor Renal Function & BP

Question 3

What drugs should we be careful of when treating hypertension and why? [2]

Answer 3

ACEIs can be nephrotoxic

Thiazides or TTDs can raise urea, coupled with renal disease this can lead to gout.

Question 4

In terms of Drug induced renal disease, why are the kidneys so sensitive to drugs?

Answer 4

Drugs cleared by the kidney get highly concentrated in the tubules leading to the kidney having the highest drug conc. per surface area anywhere in the body

Question 5

What are the two most common Drug induced renal problems? Describe how the drug causes renal problems [4]

Answer 5

Aminoglycosides induce ATN –> AKI

NSAIDs reduce renal prostoglandins –> Renal vasoconstriction –> Pre-renal AKI. (particularly bad in hypotension or renal disease)

Question 6

What drugs can induce a nephrotic syndrome? [3]

Answer 6

Gold
Penicillamine
NSAIDs

Question 7

NSAIDs can cause… [5]

Answer 7

Nephrotic Syndrome
AKI (Pre-renal or intrinsic i.e. acute interstitial nephritis)
Hypertension
Hyperkalemia
Papillary Necrosis

Question 8

What drugs can cause a post-renal AKI? [3]

Answer 8

Acyclovir, sulphonamides and large doses of vit C can all cause crystals to form in the ureters or tubules