Pharmacokinetics and prescribing in renal impairment

Question 1

most drugs follow what order elimination kinetics

Answer 1

first order elimination kinetics

Question 2

clearance describes what

Answer 2

Clearance describes the volume of blood cleared of a substance per unit time

Question 3

volume of distribution describes

Answer 3

Volume of distribution describes a theoretical volume to which a drug distributes

Question 4

A major component of drug elimination is renal clearance

- Renal clearance can be estimated by

Answer 4

Creatinine-Clearance

Question 5

Digoxin is a medication used for its negative chronotropic and positive inotropic effect (slows rate, increases contractility).
Digoxin is normally given as a loading dose on day one (1mg) followed by a maintenance dose thereafter (125mcg/day)

You wish to prescribe Digoxin to a patient with a creatinine clearance of 50mls/min (normal 100mls/min)

How should you prescribe this medicine?

Reduce loading dose by 50%, reduce maintenance dose by 50%
Maintain loading dose, reduce maintenance dose by 50%
Reduce loading dose 50%, continue standard maintenance dose

Answer 5

Maintain loading dose, reduce maintenance dose by 50%

In this case Cr is lower than 90 so reduced renal function
reducing the loading dose would not saturate enough
due to reduced renal function elimination will be slower so reduce the drug

Loading dose is based on volume of distribution (amount needed to saturate the system)
Maintenance dose is based on rate of elimination and half life

Question 6

what is loading dose based off

Answer 6

Loading dose is based on volume of distribution (amount needed to saturate the system)

Question 7

what is maintenance dose based off

Answer 7

Maintenance dose is based on rate of elimination and half life

Question 8

A patient with renal failure develops a UTI. Their GFR is 15mls/min

The patient is treated with Nitrofurantoin (an antibiotic) but this yields little clinical benefit. You send off an MSU, it shows an E.coli fully sensitive to Nitrofurantoin as well as Trimethoprim, Amoxicillin and Co-amoxiclav.

Using the BNF, renal drug handbook or one of the pharmacology texts, why do you think the patient has failed to respond to this treatment?

Answer 8

• Nitrofurantoin – 80% bioavailable, but does not concentrate in plasma (virtually undetectable)
• This is due to rapid destruction in tissues and rapid renal elimination (half life <20 mins)
• Nitrofurantoin is therapeutic because it accumulates in the urine on its path to excretion
• Patients with a GFR <60 do not accumulate enough nitrofurantoin in the urine to be therapeutic

Question 9

You are working in general practice and see a patient with chronic kidney disease (eGFR 10mls/min). They have no other significant medical history, but complain of peripheral oedema. They have been on Furosemide 40mg OM (a loop diuretic) for six weeks with little effect.

With regards to loop diuretic dosing, what changes are likely to be made accounting for the renal impairment?

a) Continue the standard dose of diuretic
b) Give a reduced dose of diuretic
c) Give an increased dose of diuretic

Answer 9

Give an increased dose of diuretic

• Loop diuretics are secreted by tubules into urine
• CKD and suboptimal nephron function means increased doses are needed to achieve therapeutic tubular concentrations

Question 10

A patient with CKD and a GFR of 10mls/min presents with deep venous thrombosis.

You elect to treat the patient with unfractionated heparin.
The normal dose is 10000 units loading followed by 18 units/kg/hour

Accounting for the renal failure, how should this medication be prescribed?
(You may wish to use the BNF or texts)

a) Reduce loading dose, give normal maintenance dose
b) Normal loading dose, reduce maintenance dose
c) Normal loading dose, normal maintenance dose

Answer 10

Normal loading dose, normal maintenance dose

• Heparin is metabolised in the liver and eliminated by the reticuloendothelial system
• In large doses/overdose, heparin becomes detectable in the urine