Pharmacology of CKD

Question 1

Bioavailability definition

Answer 1

The fractional extent to which a dose of a drug reaches its site of action

Question 2

CKD impact on absorption

Answer 2

In general, there is no major impact

Except in a patient with severe, generalized, pitting edema who may have gut edema that reduces/slows oral absorption

Question 3

Factors influencing distribution

Answer 3

Lipid solubility
Molecular weight
pH gradients
Protein binding (most important)

Question 4

How does phenytoin need to change in CKD?

Answer 4

Phenytoin has 0 order kinetics
Hypoalbuminuria results in a higher risk of toxicities
Adequate seizure control can be obtained at concentrations below the normal reference range

Question 5

How does digoxin need to change in CKD?

Answer 5

Digoxin is significantly eliminated by the kidneys and uremia results in decreased tissue binding
The result is that the concentration increases in systemic circulation - so need to decrease the dose

Question 6

Volume of distribution definition

Answer 6

The theoretical volume of fluid into which the total drug administered would have to be diluted to produce the concentration in the blood

Question 7

Are drugs with a
1. Small Vd (<1 L/kg)
2. Large Vd (>2 L/kg)
more or less likely to be eliminated by dialysis

Answer 7

1. More likely (water soluble and remain in circulatory system)
2. Less likely (lipid soluble and distribute into extravascular tissue)

Question 8

What are the rules for drug dosing based on renal or non renal drug clearance?

Answer 8

If non-renal clearance is large (>70%), then you use normal drug dosing
If renal clearance is significant (>30%), then the drugs half like will be prolonged with reduced GFR and you need to adjust the dose

Question 9

Size of drugs that can filter through the glomerulus

Answer 9

< 60,000 Da

Cannot go through if bound to proteins