Pharmacology Principles and Prescribing in Liver Failure

Question 1

What is meant by (apparent) volume of distribution?

Answer 1

the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that is observed in the blood plasma.

Question 2

What is the equation for volume of distribution?

Answer 2

Vd = amount of drug in body/plasma concentration of drug

Question 3

If a drug has a small volume of distribution what does this mean?

Answer 3

it means that the drug will remain mainly in central compartments so the concentration of it in these compartments will be greater

Question 4

if a drug has a large volume of distribution what does that mean?

Answer 4

distributes widely into body compartments and as it does so the concentration of the drug decreases. So, with a drug with a large Vd, the drug will be more concentrated in tissues outside of the bloodstream.

Question 5

how can you rearrange the volume of distribution equation to work out how much drug is in the body?

Answer 5

Vd (volume of distribution) = Ab (amount in body)/Cp(concentration in plasma)
Ab = Vd x Cp

Question 6

are loading doses usually required in drugs that have a high or low Vd and why?

Answer 6

high Vd because it has more space to fill so a loading dose is needed to achieve a target initial concentration

Question 7

describe the two compartment model and what each compartment consists of

Answer 7

Pharmacokinetic two-compartment model divides the body into central and peripheral compartment. The central compartment (compartment 1) consists of the plasma and tissues where the distribution of the drug is practically instantaneous. The peripheral compartment (compartment 2) consists of tissues where the distribution of the drug is slower.

Question 8

what is meant when a drug reaches a steady state?

Answer 8

that the rate of elimination is equal to the rate of input (dose)

Question 9

what is meant by oral availability?

Answer 9

The fraction of drug that reaches the systemic circulation after oral ingestion.
it is determined by ‘absorption’ and ‘first pass metabolism’.
absorption refers to the ability of the drug to cross the gut wall into the portal vein

Question 10

what is meant by first pass metabolism?

Answer 10

pre-systemic drug elimination. it can occur in the gut wall, portal vein or liver. the liver is usually the most important contributor.

Question 11

name an important group of efflux pumps in the intestine

Answer 11

ATP-binding cassette (ABC)
p-glycoprotein (P-gp)
breast cancer resistance protein (BCRP)
multidrug resistance protein (MRP2)

Question 12

what is the role of efflux pumps in drug absorption?

Answer 12

they actively decrease absorption of a drug in the gut or prevent drugs enetering certain compartmetns (e.g. the brain) but they can also be targeted and inhibited to mean more drug gets absorbed

Question 13

can different formulations of drugs have different oral bioavailability?

Answer 13

Yes - this is why care needs to be taken when prescribing drugs if they come in standard and modified release formulations

Question 14

Why might liver damage affect oral bioavailability?

Answer 14

first pass metabolism will be reduced/slower so bioavailability of a drug will be increase

Question 15

what needs to be known about a drug in order to know the desired concentration steady state in a patient?

Answer 15

know the drug’s clearance and bioavailability.

Concentration steady state = (dose x bioavailability)/(timex clearaance)

Question 16

what 6 effects can liver disease potentially have on prescribing?

Answer 16

1. impaired drug metabolism
2. hypoproteinaemia
3. reduced blood coagulation
4. hepatic encephalopathy
5. fluid overload
6. hepatotoxic drugs

Question 17

what is the link between plasma concentration, dose rate and clearance?

Answer 17

plasma concentration (Cp) = dosre rate/clearance

Question 18

what is meant by first order kinetics/elimination?

Answer 18

where the amount of drug eliminated per unit time is proportional to the drug concentration. so, a constant %age of the drug is eliminated per unit time

Question 19

what is meant by zero order kinetics/elimination?

Answer 19

the amount of drug eliminated is constant per unit time and not related to the concentraion. this is saturation kinetics. if the metabolising enzymes becoem saturated, no further increase in the rate of metabolism can occur

Question 20

a drug is in first order kinetics then the enzyme metabolising it becomes saturated so what type of kinetics does it move to?

Answer 20

zero order - the metabolising enzymes have become saturated so no further increase in the rate of metabolism can occur

Question 21

two oral formulations of digoxin have different oral bioavailabilities:
tablets: F = 0.63
Liquid: F=0.75
if the patient has been taking 125 micrograms of oral tablets but needs to change to liquid formulation whcih is available in 50 microgram/mL solution, how much of the liquid solution (in mLs) will you need to maintain the same serum digoxin concentration?

Answer 21

63% of 125 gets into system:
125 x 0.63 = 78.75 micrograms

78.75/0.75 = 105 micrograms

1ml has 50mg so 105/50 = 2.1mL

or another way:

125 x (0.63/0.75) = 105 micrograms
105/50 = 2.1mL