Pharmacology Principles and Prescribing in Liver Failure Flashcards
What is meant by (apparent) volume of distribution?
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.
What is the equation for volume of distribution?
Vd = amount of drug in body/plasma concentration of drug
If a drug has a small volume of distribution what does this mean?
it means that the drug will remain mainly in central compartments so the concentration of it in these compartments will be greater
if a drug has a large volume of distribution what does that mean?
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.
how can you rearrange the volume of distribution equation to work out how much drug is in the body?
Vd (volume of distribution) = Ab (amount in body)/Cp(concentration in plasma)
Ab = Vd x Cp
are loading doses usually required in drugs that have a high or low Vd and why?
high Vd because it has more space to fill so a loading dose is needed to achieve a target initial concentration
describe the two compartment model and what each compartment consists of
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.
what is meant when a drug reaches a steady state?
that the rate of elimination is equal to the rate of input (dose)
what is meant by oral availability?
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
what is meant by first pass metabolism?
pre-systemic drug elimination. it can occur in the gut wall, portal vein or liver. the liver is usually the most important contributor.
name an important group of efflux pumps in the intestine
ATP-binding cassette (ABC)
p-glycoprotein (P-gp)
breast cancer resistance protein (BCRP)
multidrug resistance protein (MRP2)
what is the role of efflux pumps in drug absorption?
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
can different formulations of drugs have different oral bioavailability?
Yes - this is why care needs to be taken when prescribing drugs if they come in standard and modified release formulations
Why might liver damage affect oral bioavailability?
first pass metabolism will be reduced/slower so bioavailability of a drug will be increase
what needs to be known about a drug in order to know the desired concentration steady state in a patient?
know the drug’s clearance and bioavailability.
Concentration steady state = (dose x bioavailability)/(timex clearaance)