Pharmacokinetics and prescribing in renal impairment Flashcards
elimination
removal of a substance from the plasma
what is clearance?
volume of blood which is cleared of a substance per unit of time
excretion
removal of a substance from the body
bioavailability
% of drug reaching the systemic circulation
volume of distribution
theoretical volume to which a drug distributes into
how much it dilutes and distributes into cells and interstitial fluid
theoretical as the volume can often be much greater than patient’s total body mass
what are the patterns drug elimination followd?
first order
zero order
first order elimination
elimination is dynamic and proportional to plasma drug concentration
zero order elimination
elimination is constant and related to rate of product derived from saturated kinetics
clearance
different from GFR which is only kidney excretion
this is renal clearance + hepatic clearance + respiratory clearance
GFR
how much filtrate is produced per unit of time
mls/min
normal GFR
> 90ml/min
hepatic clearance
bile salts
what determines clearance
for each organ clearance is dependent on blood flow and extraction ratio
what is extraction ratio?
what % of blood delivered is cleared of a substance in each pass - each time it passes through the organ
renal clearance
contributes the majority of clearance for most substances and drugs
renal impairment is therefore very important in drug elimination
how to calculate volume of distribution?
divide plasma concentration of drug/dose administered
giving a volume in ml and then expressed in litres
what can volume of distribution be used for?
to anticipate how a drug will distribute itself throughout the bodies tissues
VD 0-5L
suggests drug is confined to vascular compartment - highly protein bound
VD 5-15L
suggests drug is distributed in the vascular and extracellular compartment - moderately protein bound and highly polarised
VD >15L
suggests the drug is distributed throughout the bodily tissues including within cells
it is electrically neutral and lipid soluble
half life
the observed time it takes for the concentration of a drug in plasma to fall by half its original value
what affects half life?
half-life is dependent on drug clearance and drug volume of distribution
rate of elimination
describes the amount of drug removed per unit of time
how to calculate rate of elimination?
clearance x plasma concentration to give mg/min
what affects rate of elimination?
dependent on clearance and the amount of drug in the vascular space
half life of first order kinetic drugs
takes 4-5 half lives to reach steady state of elimination
medications with a long half life require a prolonged period of initiation before the therapeutic concentration is reached
how to overcome medications with long half lives?
loading dose - big dose to saturate the system - based on VD
then smaller maintenance doses given daily to replenish what is eliminated - based on clearance and VD
what is renal clearance?
the capacity of the kidneys to clear blood of a given substance per unit of time
how to estimate renal clearance?
use creatinine - creatinine-clearance
on results shown as EGFR (estimated GFR)
what makes creatinine useful to estimate clearance?
produced at a relatively constant rate
freely filtered
not reabsorbed
however, secreted in small amounts by tubules
deriving creatinine clearance
Cockcroft-gault equation
in ml/min
how to calculate ideal body weight?
50 or 45.5 (males and females) + [2.3 x (height in inches - 60)]
why do drugs need to be altered in renal failure?
potential for accumulation - unwanted side effects
resistance to action - due to saturation
direct nephrotoxicity
what to check for prescribing in renal failure?
BNF
renal drug handbook
what does digoxin do?
negative chronotropic - slows HR
positive inotropic - increases contractility
what is normal creatinine clearance?
100ml/min
with regards to loop diuretics dosing what changes are likely to be made accounting for the renal impairment
increased dose of diuretic needed to achieve therapeutic tubular concentrations
loop diuretics are secreted by tubules into urine
need to be stopped in acute kidney injury
loading dose and maintenance dose in renal impairment
loading dose remains the same
reduced maintenance dose because creatinine clearance/ rate of elimination has slowed down
Nitrofurantoin
does not concentrate in plasma
rapid destruction in tissues and rapid renal elimination (half life <20min)
accumulates in urine so is then effective
patients with GFR<60 do not accumulate enough in urine to be therapeutic
pylonephritis
infection spread up into kidneys from UTI
heparin prescribing in patients with chronic kidney disease
normal loading and maintenance dose
metabolised by liver and eliminated by reticuloendothelial system
in large doses heparin becomes detectable in urine
