Drug Absorption Flashcards
Pharmaceutical process
get the drug into the patient
Pharmacokinetic process
get the drug to the site action
Pharmacodynamic process
produce the correct pharmacological effect
Therapeutic process
produce the correct therapeutic effect
What are the 4 basic factors that determine drug pharmacokinetics?
- absorption
- distribution
- metabolism
- elimination
What does ADME enable us to understand?
- dosage
- drug administration
- drug handling
- patient variability
- potential for harm
Absorption
- the process of movement of unchanged drug from the site of administration to the systemic circulation
- there is always a correlation between plasma concentration of a drug and the therapeutic response
How can drugs be absorbed?
- oral
- IV
- IM
- other GI- sublingual, rectal
- inhalation
- nasal
- transdermal
What are important issues to consider with oral absorption?
- amount of drug which enters the systemic circulation
- speed at which this happens
What is Tmax?
- the time to peak concentration
- the more rapid the rate of absorption, the earlier the drug concentration peak
What is Cmax?
- peak concentration
- increasing dose does not affect the time at which peak concentration is reached but does increase peak concentration
What is AUC?
-are under the drug concentration time curve represents the amount of drug which reaches the systemic circulation
Therapeutic range
a drug is active over a range of concentrations
What happens outwith the therapeutic range?
- below this there will insufficient or no pharmacological action
- above this toxicity occurs
Therapeutic index
a measure of the range at which a drug is safe and active
Bioavailability
the amount of drug which reaches the circulation and which is available for action
What method of administration has 100% bioavailability?
IV
Factors affecting bioavailability
- formulation
- ability of the drug to pass physiological barriers
- gastrointestinal effects
- first pass metabolism
How can drugs be transported across membranes?
- passive diffusion
- filtration
- bulk flow
- active transport
- facilitated diffusion
- ion-pair transport
- endocytosis
What is the degree of ionisation of a drug dependent on?
environment
What will happen to the un-ionised form of the drug?
It will cross the membrane and should distribute across the membrane until equilibrium is reached- an equal concentration at each side
What is ion trapping?
an acidic drug will be more concentrated in the compartment with high pH
What is the Henderson Hasselbalch equation?
the relationship between the local pH and the degree of ionisation
What is the result of the Henderson Hasselbalch equation?
small changes in pH may significantly influence the ionisation of a drug and so the rate of absorption or diffusion
Aspirin is a weak acid, so should be absorbed more easily from the stomach. Why is it not?
-There may be more important factors such as available gut surface are, so in fact aspirin is more absorbed from the small intestine. Even though it is ionised and less lipid soluble.
What must a drug be to pass across a lipid layer?
- in solutions
- lipid soluble
How is the ability of a drug to diffuse across a lipid barrier expressed?
lipid-water partition coefficient
What is the lipid-water partition coefficient?
the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact
Compare the diffusion of lipid soluble vs not lipid soluble.
- a drug that is highly lipid soluble will rapidly diffuse across a cell membrane- reach the brain, ovaries, testes and liver
- a drug that is not lipid soluble may not be absorbed at all, for example gentamicin
What must be true of the drugs fro them to undergo active transport?
they must resemble naturally occurring compounds
Where does filtration usually occur?
through channels in the cell membrane
What is the driving force for the passage of drugs in filtration?
hydrostatic or the osmotic pressure difference across the membrane
