Pharmacokinetics in Chronic Kidney Disease Patients

Question 1

Renal
Hepatic
Absorption
Distribution

Answer 1

Almost all slowed
Slowed of some
Increased of certain
Volume of distribution and plasma protein binding sometimes altered

Question 2

CKD renal drug elimination effects

Answer 2

Decreases elimination if undergoes GFR or tubular secretion

If mixed, then extra caution if kidnyes 30-40

Question 3

Most common used parameter to measure drug clearance

Answer 3

GFR

Renal elimination - scale linearly with GFR

If both - then scales linearly with changes in GFR and hepatic compoentn when GFR=0

Question 4

Hepatic effects

Answer 4

Largest decreases - CYP2C19, CYP3A4, N-acetyltransferares

Moderate - CYP2d6, glucuronyltransferases

Hepatic effects of accumulating uremic toxins may be involved

Question 5

Separate CKD effect

Answer 5

Hepatic metabolism converts a hydrophobic drug to hydrophilic metabolite…CKD allows it to accumulate and toxicity occurs

Question 6

CKD and oral bioailability

Answer 6

Most likely to occur when enzymatic activity decreases oral drug’s first pass effect…parenteral administration can bypass

Question 7

PLasma protein binding effects

Answer 7

Acidic drugs displaced from albumin by acids that accumulate

Highly bound weak acids with low therparutic index likely to be clinically significant (valproic acid)

More free drug so more pharm effect

Normal value for total drug but more free drug

Question 8

Chronic kidney dz and volume of distribution

Answer 8

Expansion of ECV - increased Vd…hydrophilic drugs that stay EC

Decreased binding to plasma proteins…increase…highly bound acidic drugs

Altered binding of drug to tissues…increase or decrease…digoxins tissue binding decreases in CKD

Question 9

Adjustment of maintenance doses in CKD

Answer 9

Adjust dosage amount, interval, or both

Trying to maintain same average plasma drug concentration

Question 10

Adjusting dosage amount

Answer 10

Dose decreased in proportion to renal function

Avwrage drug concentration stays same but max is lower than normal and min is higher than normal

Question 11

Adjusting interval

Answer 11

Interval scaled to proportion to renal function

Max, min and average are same as normal but drug concentration may be sub therapeutic or near toxic level for long periods

Question 12

Combination adjustment

Answer 12

Average same as normla

Max and min are closer than with dosage

Subtherapeutic or near toxic are shorter than with interval

Question 13

Adjustment of loading doseases

Answer 13

More drugs need loading doses in CKD

During IV infusion, drug undergoes exponential rise to SS concentraiton

CKD slows this so it takes longer

T1/2 becomes longer

Question 14

Loading dose calculation and when is it unaffected

Answer 14

Therapetuci plasma concentration=loading dose/Vd

Unaffected if therpatuic conenctration unchanceg and Vd unchanged