M&R S9 - Pharmacokinetics Flashcards
Define pharmacokinetics
What the body does to the drug
What are the different ‘formulations’ of drugs?
Solid or liquid
What are the different sites of administration on a patient?
Make sure to split them into their categories and name the categories
Focal:
- Eye
- Skin
- Inhalation
Systemic:
- Enteral (Sublingual, oral, rectal)
- Parenteral (Subcutaneous, intramuscular, intravenous, transdermal, inhalation)
What is bioavailability?
The proportion of the done given by any route other than intravenously that reaches the systemic circulation in an unchanged form
How is bioavailability expressed?
Can be expressed as an amount or rate
Amount:
- Depends on G.I. absorption and first pass metabolism
- Measured by area under the curve of a blood drug level vs time plot
Rate:
- Depends on pharmaceutical factors and rate of gut absorption
- Measured by peak height and rate of rise of a drug level in blood
Define therapeutic ratio
Define LD50 and ED50
Maximum tolerated dose divided by minimum effective dose
Expressed as LD50/ED50
LD50:
- Lethal dose to 50% of people
ED50:
- Effective dose to 50% of people
Describe the 1st pass effect
Substances absorbed from the lumen of the ileum enter venous blood
This drains into the portal vein and is transported directly to the liver
Liver is the main site of drug metabolism, containing all the necessary enzyme systems
Any drug absorbed from the ileum may therefore be subject to extensive metabolism before reaching the systemic circulation
How can the First pass effect be avoided?
Give an example of a drug extensively metabolised during first pass metabolism
Parenteral, sublingual and rectal routes avoid it
Oral paracetamol, 90% on first pass
Define volume of distribution
How is it calculated?
The theoretical volume into which a drug has distributed assuming that this has occurred instantaneously
Amount given divided by plasma [drug] at time 0
Describe how drugs are affected by protein binding in the blood
Many drugs bind to plasma proteins and protein binding interactions could occur
Only the drug free in plasma exerts effect
They are therefore important if:
- Drug is highly bound to albumin (>90%)
- Drug has a small volume of distribution
- Drug has a low therapeutic index
What are protein binding interactions?
How are they used therapeutically?
The interactions between different drugs binding to plasma proteins, determining the relative proportion of each drug that is bound to plasma proteins
An object drug is used at a dose that is lower than albumin binding sites
A precipitant drug is then used at a dose which is greater than the number of albumin binding sites
Adding the precipitant drug will temporarily lead to higher levels of the object drug free in plasma as the precipitant drug occupies albumin binding sites (there is therefore higher risk of toxicity)
Give examples of object drugs and their respective precipitants
Object = Warfarin Precipitants = Sulphonamides, aspirin, phenytoin
Object = Tolbutamide Precipitants = Sulphonamides, aspirin
Object = Phenytoin Precipitant = Valproate
What is meant by first order kinetics?
When do they apply?
Means metabolism of a drug is proportional to drug concentration
Applies when:
- Drug is being metabolised by an enzyme that obeys Michaelis-Menten kinetics
- The drug is used at a lower concentration than Km
Describe how [drug] appears when plotted against time in a graph
Assume first order kinetics of drug metabolism
Gives a straight line when plotted on a log scale against time
Half life can be found because the rate of metabolism is proportional to [drug]
What is meant by zero order kinetics?
When do they apply?
Rate of decline of plasma [drug] is constant regardless of concentration as enzyme is saturated
Applies when:
- Drug is being metabolised by an enzyme that obeys Michaelis-Menten kinetics
- The [drug] is much greater than Km
