Session 6: Renal

Question 1

What is used to determine the magnitude of renal drug clearance

Answer 1

The sum of glomerular filtration and active excretion, minus renal drug absorption.

Question 2

What are the 4 stages of renal drug clearance?

Answer 2

1. Filtration. Plasma is excreted (around 125ml/min)
2. Reabsorption. Useful materials (solutes, water) are reabsorbed
3. Secretion. Metabolic waste products may be secreted, too.
4. Excretion. Remainder is excreted as urine.

Question 3

Which factors affect renal drug clearance?

Answer 3

Glomerular filtration: Size, charge, protein binding, renal blood flow, age

Tubular reabsorption: drug concentration, urine flow rate, urine pH, drug ionisation

Active secretion: protein binding, renal blood flow, competition between substrates, concentration of drug.

Question 4

In terms of Pharmacokinetics, how are the following effected:

Absorption and Bioavailability
Distribution
Metabolism
Elimination

Answer 4

A&B:
1. ureamia - diarrhoea and vomiting
2. increase in gastric pH- reduced bioavailability of drugs require acidic environment
3. reduced expression of CYPT450 and p-glycoprotein

D:
1. Hydration
2. Protein binding, volume of distribution

M:
1. Reduction, hydrolysis, and conjugation of some drugs affected-including levels of parent drug
2. Enzymes
3. half-life

E?

Question 5

What advice is given when prescribing in renal impairment?

Answer 5

-Give standard dose at extended intervals (used when precise dose needed e.g. preventing antibiotic resistance)
-A reduced dose given at the usual intervals (enough to maintain function but not OD e.g. apixaban)
-A combination of extended interval and standard dose