Prescribing in renal failure Flashcards
Clearance
Volume of blood cleared of a substance per unit time
Elimination
Removal of a substance from plasma
Excretion
Removal of a substance from body
Bioavailability
% of drug reaching systemic circulation
Volume of distribution
Theoretical volume to which a drug distributes to
Total clearance
Renal clearance + respiratory clearance
GFR
How much filtrate is produced per unit time
Half-life
Observed time for concentration of drug to fall by half of its original value - normally 4-5 to reach steady state
Rate of elimination
Amount of drug removed per unit time
Loading dose
First dose to saturate system (based on VD)
Maintenance dose
Replenish what is eliminated
Renal clearance
Capacity of kidneys to clear blood of given substance per unit time - creatinine used as surrogate
Why is creatinine used as surrogate?
Produced at constant rate, freely filtered and not reabsorbed
What is the name of the equation to calculate creatinine clearance?
Cockcroft-Gault
First order drug elimination
Elimination is dynamic and proportional to plasma drug concentration - curve
Zero order drug elimination
Elimination is constant and related to rate of product derived from saturated kinetics
How to calculate rate of elimination
Clearance x plasma concentration
What is volume of distribution
Volume into which a drug distributes into
Divide plasma concentration of drug by dose administered to leave volume
What does VD 0-5L show?
Drug confined to vascular compartment
What does VD 5-15L show?
In vascular and extracellular compartments
What does VD >15L show?
Distributed throughout body
How do we have to change drugs in renal failure?
Potential for accumulation
Resistance to action
Direct nephrotoxicity
Which order kinetics do most drugs follow?
First order
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?
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
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?
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
Pt has CKD with peripheral oedema, Furosemide has little effect, what changes should you make?
Increase dose of diuretic
Loop diuretics are secreted by tubules into urine
CKD and suboptimal nephron function means increased doses needed
Pt has CKD and DVT, you want to treat with heparin, how should this be prescribed?
Normal loading and maintenance doses
Heparin metabolised in liver and eliminated by reticuloendothelial system
In large doses it is detectable in urine
