How can renal disease affect drug action?
Pharmacokinetic:
- Less clearance –> Increased Half life –> Raised plasma levels
- 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 tendancy due to loss of anti-thrombin. Beware NSAIDs & warfarin
How do we take renal disease into account when prescribing?
- Use drugs that are safe at a low GFR
- 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
- Avoid anything nephrotoxic
What drugs should we be careful of when treating hypertension and why?
ACEIs can be nephrotoxic
Thiazides or TTDs can raise urea, coupled with renal disease this can lead to gout.
In terms of Drug induced renal disease, why are the kidneys so sensitive to drugs?
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
What are the two most common Drug induced renal problems?
Aminoglycosides induce ATN –> AKI
NSAIDs reduce renal prostoglandins –> Renal vasoconstriction –> Pre-renal AKI. (particularly bad in hypotension or renal disease)
What drugs can induce a nephrotic syndrome?
Gold
Penicillamine
NSAIDs
NSAIDs are fucking wild, what else can they cause?
Nephrotic Syndrome AKI (Pre-renal or intrinsic i.e. acute interstitial nephritis) Hypertension Hyperkalemia Papillary Necrosis
What drugs can cause a post-renal AKI?
Acyclovir, sulphonamides and large doses of vit C can all cause crystals to form in the ureters or tubules
