NEPH 03: Drug Therapy Individualization in CKD

1) Where are most oral medications absorbed?

2) Why? (3)

1) Small intestine —> Mostly duodenum

2) Large surface area, good blood flow, digestive enzymes to help break down drugs for absorption

How does CKD increase drug absorption and bioavailability

1) Increased intestinal pH —> Drugs may be better absorbed in less acidic environment

2) Gut is more permeable —> Leaky gut allows drugs to pass through slits

3) Less efflux proteins —> Fewer drugs are kicked out when they go into cells

4) Less CYP3A2 —> Drugs are not being broken down as much

1) What drugs do H2 blockers that reduce stomach acid affect

2) What drugs are affected when there’s edema in the GI tract

3) What drugs are affected when there’s antacids (calcium) / phosphate binders

4)

a) What is P-gp

b) Examples of P-gp inhibitors (4)

c) Drugs affected by P-gp inhibitors (4)

1) Decrease absorption of iron and ketoconazole

2) Decrease absorption of furosemide (diuretic)

3) Decrease absorption of Ciprofloxacin and L-thyroxine

4)

a) Protein that pumps drugs back into gut lumen reducing drug absorption

b) Cyclosporine, tacrolimus, clarithromycin, amiodarone

c) INCREASE absorption of Dabigatran, rivaroxaban, apixaban, digoxin

1) How does CKD affect free phenytoin levels

2) Explain why

3) What can we do to counter this

4) At normal albumin levels, total phenytoin is ____

5) What percentage of total phenytoin is free

6) Normal albumin = How much free phenytoin

7) What does a high corrected level indicate

1) Increase in free phenytoin

2) Since there’s a decrease in albumin in CKD, phenytoin cannot bind to albumin. This leads to more of it being in its “free” active form

3) Give a decreased dose of phenytoin

4) Between 40-80mmol/L

5) 10%

6) 4-8mmol/L

7) Indicates that the free phenytoin concentration is likely elevated

CKD reduces the livers ability to metabolize + conjugate drugs

1. What does this increase the risk of

2. Give one example of a drug

1) Higher risk of accumulating active metaboliges

2) Meperidine

What type of drugs can be filtered through the glomerulus

Small molecules of low molecular weight

Free drugs that are NOT protein bound

What drug(s) can block the secretion of serum creatinine by competing for the same transport system (2)

—> SCr levels rise

Trimethoprim and cimetidine

What drug can increase levels of penicillin type drugs (to extend duration of action)

Probenecid

When is dose adjustments necessary in CKD

—> Give 2 drug examples

If >40-50% of a drug or its active metabolite is eliminated by the kidneys AND

the kidney function is reduced (eGFR < 50 mL/min)

—> Gabapentin + Valganciclovir