Prescribing in renal failure

Question 1

Clearance

Answer 1

Volume of blood cleared of a substance per unit time

Question 2

Elimination

Answer 2

Removal of a substance from plasma

Question 3

Excretion

Answer 3

Removal of a substance from body

Question 4

Bioavailability

Answer 4

% of drug reaching systemic circulation

Question 5

Volume of distribution

Answer 5

Theoretical volume to which a drug distributes to

Question 6

Total clearance

Answer 6

Renal clearance + respiratory clearance

Question 7

GFR

Answer 7

How much filtrate is produced per unit time

Question 8

Half-life

Answer 8

Observed time for concentration of drug to fall by half of its original value - normally 4-5 to reach steady state

Question 9

Rate of elimination

Answer 9

Amount of drug removed per unit time

Question 10

Loading dose

Answer 10

First dose to saturate system (based on VD)

Question 11

Maintenance dose

Answer 11

Replenish what is eliminated

Question 12

Renal clearance

Answer 12

Capacity of kidneys to clear blood of given substance per unit time - creatinine used as surrogate

Question 13

Why is creatinine used as surrogate?

Answer 13

Produced at constant rate, freely filtered and not reabsorbed

Question 14

What is the name of the equation to calculate creatinine clearance?

Answer 14

Cockcroft-Gault

Question 15

First order drug elimination

Answer 15

Elimination is dynamic and proportional to plasma drug concentration - curve

Question 16

Zero order drug elimination

Answer 16

Elimination is constant and related to rate of product derived from saturated kinetics

Question 17

How to calculate rate of elimination

Answer 17

Clearance x plasma concentration

Question 18

What is volume of distribution

Answer 18

Volume into which a drug distributes into

Divide plasma concentration of drug by dose administered to leave volume

Question 19

What does VD 0-5L show?

Answer 19

Drug confined to vascular compartment

Question 20

What does VD 5-15L show?

Answer 20

In vascular and extracellular compartments

Question 21

What does VD >15L show?

Answer 21

Distributed throughout body

Question 22

How do we have to change drugs in renal failure?

Answer 22

Potential for accumulation
Resistance to action
Direct nephrotoxicity

Question 23

Which order kinetics do most drugs follow?

Answer 23

First order

Question 24

Digoxin is normally given as loading dose on day 1, followed by maintenance dose after. You wish to prescribe digoxin to a pt with creatinine clearance of 50mls/min, how should you prescribe this medication?

Answer 24

Maintain loading dose, reduce maintenance dose by 50%
Loading dose is based on VD
Maintenance dose is based on rate of elimination and half life

Question 25

A pt with renal failure develops a UTI, they are treated with nitrofurantoin but no benefit because they have an e.coli sensitive to nitrofurantoin - why do you think pt has failed to respond to treatment?

Answer 25

Nitrofurantoin -80% bioavailable, doesn’t concentrate in plasma
Rapidly destroyed in tissues and rapid renal elimination
Nitrofurantoin accumulates in urine on path to excretion
Pt with low GFR don’t accumulate enough nitrofurantoin for it to be therapeutic

Question 26

Pt has CKD with peripheral oedema, Furosemide has little effect, what changes should you make?

Answer 26

Increase dose of diuretic
Loop diuretics are secreted by tubules into urine
CKD and suboptimal nephron function means increased doses needed

Question 27

Pt has CKD and DVT, you want to treat with heparin, how should this be prescribed?

Answer 27

Normal loading and maintenance doses
Heparin metabolised in liver and eliminated by reticuloendothelial system
In large doses it is detectable in urine