Session 9 - Pharmacokinetics Flashcards
How do we calculate bioavailability?
Area under curve oral / Area under curve injected x100
The curve of plasma drug conc vs time
How do we calculate therapeutic ratio?
Maximum tolerated dose / Minimum effective dose
What is thee first pass effect?
Drugs taken orally pass to the ileum. They are absorbed here and enter the liver by the Hepatic Portal Vein. Here drugs may be extensively metabolised during their first pass through the liver
Which routes of administration can avoid the first pass effect?
Parenteral, sublingual or rectal
What is drug distribution?
The theoretical volume into which a drug distributes assuming that this occurs instantaneously
How do we work out the plasma concentration of a drug a time 0?
And how do we then use this to calculate the drug distribution value?
Extrapolate the graph of plasma concentration against time back to zero.
Divide the amount given of the drug in total by the plasma concentration at zero to give the drug distribution value
When will a drug exert its effect, when bound to a plasma protein or when free?
The free level of the drug is the amount that can exert its effect
When are protein binding actions important?
- Drug is highly bound to albumin (>90%)
- Drug has a low volume of distribution
- Drug has a low therapeutic index
When may be use a precipice the drug as well as our object drug?
And how does this work?
To increase the amount of free drug in the plasma
This works by the precipitation drug being given at a much higher does. This binds to albumin meaning that all of the binding sites are used meaning that the object drug has a much higher free concentration.
When can using a precipitant drug as well as the object drug be dangerous?
If the object drug has a normally high level bound to albumin it can mean that the free levels quickly reach the toxic concentration of the drug
With a drug that follows first order kinetics what will happen if we increase the amount drug in terms of rate of metabolism?
The rate of metabolism will increase
With a drug that follows zero order kinetics what will happen if we increase the amount drug in terms of rate of metabolism?
As we increase the concentration of drug the metabolism will not be effected in any way
What about the metabolism of drugs in the liver makes us able to manipulate the rate of metabolism?
The enzymes involved are high inducible or inhibitable, meaning that we can effect how quickly they are metabolised
How could we increase the rate in which Warfarin in metabolised?
Give the patient Phenobarbitone which will induce the enzymes involved in Warfarin metabolism
What molecule is an enzyme inducer for the Oral Contraceptive?
And why can this be a big issue?
Rifampicin
If this is taken soon after the oral contraceptive pill it can induce the metabolism enzymes resulting in the contraceptive not working and the patient still being pregnant. This is a possibility as Rifampicin is present in some antibiotics
