Pharmacokinetics and prescribing in renal impairment

Question 1

elimination

Answer 1

removal of a substance from the plasma

Question 2

what is clearance?

Answer 2

volume of blood which is cleared of a substance per unit of time

Question 3

excretion

Answer 3

removal of a substance from the body

Question 4

bioavailability

Answer 4

% of drug reaching the systemic circulation

Question 5

volume of distribution

Answer 5

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

Question 6

what are the patterns drug elimination followd?

Answer 6

first order

zero order

Question 7

first order elimination

Answer 7

elimination is dynamic and proportional to plasma drug concentration

Question 8

zero order elimination

Answer 8

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

Question 9

clearance

Answer 9

different from GFR which is only kidney excretion

this is renal clearance + hepatic clearance + respiratory clearance

Question 10

GFR

Answer 10

how much filtrate is produced per unit of time

mls/min

Question 11

normal GFR

Answer 11

> 90ml/min

Question 12

hepatic clearance

Answer 12

bile salts

Question 13

what determines clearance

Answer 13

for each organ clearance is dependent on blood flow and extraction ratio

Question 14

what is extraction ratio?

Answer 14

what % of blood delivered is cleared of a substance in each pass - each time it passes through the organ

Question 15

renal clearance

Answer 15

contributes the majority of clearance for most substances and drugs
renal impairment is therefore very important in drug elimination

Question 16

how to calculate volume of distribution?

Answer 16

divide plasma concentration of drug/dose administered

giving a volume in ml and then expressed in litres

Question 17

what can volume of distribution be used for?

Answer 17

to anticipate how a drug will distribute itself throughout the bodies tissues

Question 18

VD 0-5L

Answer 18

suggests drug is confined to vascular compartment - highly protein bound

Question 19

VD 5-15L

Answer 19

suggests drug is distributed in the vascular and extracellular compartment - moderately protein bound and highly polarised

Question 20

VD >15L

Answer 20

suggests the drug is distributed throughout the bodily tissues including within cells
it is electrically neutral and lipid soluble

Question 21

half life

Answer 21

the observed time it takes for the concentration of a drug in plasma to fall by half its original value

Question 22

what affects half life?

Answer 22

half-life is dependent on drug clearance and drug volume of distribution

Question 23

rate of elimination

Answer 23

describes the amount of drug removed per unit of time

Question 24

how to calculate rate of elimination?

Answer 24

clearance x plasma concentration to give mg/min

Question 25

what affects rate of elimination?

Answer 25

dependent on clearance and the amount of drug in the vascular space

Question 26

half life of first order kinetic drugs

Answer 26

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

Question 27

how to overcome medications with long half lives?

Answer 27

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

Question 28

what is renal clearance?

Answer 28

the capacity of the kidneys to clear blood of a given substance per unit of time

Question 29

how to estimate renal clearance?

Answer 29

use creatinine - creatinine-clearance

on results shown as EGFR (estimated GFR)

Question 30

what makes creatinine useful to estimate clearance?

Answer 30

produced at a relatively constant rate
freely filtered
not reabsorbed
however, secreted in small amounts by tubules

Question 31

deriving creatinine clearance

Answer 31

Cockcroft-gault equation

in ml/min

Question 32

how to calculate ideal body weight?

Answer 32

50 or 45.5 (males and females) + [2.3 x (height in inches - 60)]

Question 33

why do drugs need to be altered in renal failure?

Answer 33

potential for accumulation - unwanted side effects
resistance to action - due to saturation
direct nephrotoxicity

Question 34

what to check for prescribing in renal failure?

Answer 34

BNF

renal drug handbook

Question 35

what does digoxin do?

Answer 35

negative chronotropic - slows HR

positive inotropic - increases contractility

Question 36

what is normal creatinine clearance?

Answer 36

100ml/min

Question 37

with regards to loop diuretics dosing what changes are likely to be made accounting for the renal impairment

Answer 37

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

Question 38

loading dose and maintenance dose in renal impairment

Answer 38

loading dose remains the same

reduced maintenance dose because creatinine clearance/ rate of elimination has slowed down

Question 39

Nitrofurantoin

Answer 39

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

Question 40

pylonephritis

Answer 40

infection spread up into kidneys from UTI

Question 41

heparin prescribing in patients with chronic kidney disease

Answer 41

normal loading and maintenance dose
metabolised by liver and eliminated by reticuloendothelial system
in large doses heparin becomes detectable in urine