pharmacokinetic and ADME Flashcards
define pharmacokinetics
A branch of pharmacology that studies the kinetic change or movement of a drug in the body over time.
what does ADME stand for in pharmacokinetics?
A = Absorption
D = Distribution
M = Metabolism
E = Elimination
ADME refers to the process of a drug in the body
What is the therapeutic window?
the time range between injury and treatment during which the drug treatment is still effective
what do MTC and MEC refer to in regards to the plasma concentration of a drug
MTC = maximal tolerated concentration
MEC = minimum efficacious concentration
this image shows the ideal but impossible plasma concentration-time relationship for drug administration
why is this impossible?
unless injected intravenously, there will always be a delay between the time of administration and the drug reaching the blood plasma
how was this drug administered based on the graph?
intravenous injection
what causes the decline after the drug concentration peaks in the blood plasma
the drug is metabolised and excreted
name some absorption routes of drug administration through…
- lungs?
- gut?
- muscle?
- skin?
- lungs
inhalation of gases
- gut
Oral, Rectal, sublingual
- muscle
intramuscular injection
- skins
subcutaneous injection/cream
which of these lines shows the time course of plasma levels for:
- Oral
- i.m
- i.v.
what are the two main absorption mechanisms?
and how do they work?
passive diffusion - drugs cross the cell membrane according to their physio-chemical properties, no energy is required
active diffusion - drugs cross the cell membrane by carrier or transporter proteins
The two forms of passive diffusion are transcellular diffusion and paracellular diffusion
Whats the difference between them?
transcellular diffusion - involves permeating through the cell
paracellular diffusion - involves the drug moving in between the cells
there are 3 forms of active transport
- active efflux
- carrier-mediated transport
- endocytosis
briefly describe them
- Active efflux, certain types of transporters on the apical (external) (e.g. gut) and basal (internal) (blood) surfaces efflux the drug back to the apical side of the cell membrane.
- Carrier-mediated transport involves the uptake of the drug from the apical side of the membrane into the basal side.
- Endocytosis does not require transporter proteins but still requires energy. It involves the transport of the drug through cells via vesicles
Drug distribution is the reversible transfer of drugs between the site of measurements and other sites within the body
what are some factors which greatly determine a drug’s distribution from the blood plasma?
- lipid solubility
- membrane permeability
- Plasma Protein binding
- size
- blood perfusion (ability to travel in the blood)
- ionisation state of the drug
What tissue depots?
different tissues in the body in which drugs can accumulate, the distribution of these drugs depends on blood flow to that tissue
in the blood-brain barrier (BBB) diffusion is only possible for _____ soluble drugs, _____ soluble drugs tend to diffuse more slowly
in the blood-brain barrier (BBB) diffusion is only possible for lipid-soluble drugs, water soluble drugs tend to diffuse more slowly
the placenta controls blood flow to the foetus, what is the distribution of drugs to the foetus limited by
- lipid solubility
- size
define volume distribution (Vd)
what does a Vd > 40 litres suggest about the drug distribution?
what does Vd < 10 litres suggests about the drug distribution?
- The theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma
- Vd > 40 litres indicates storage of drug in tissues
- Vd < 10 litres suggests drug is largely restricted to plasma and interstitial fluid
what are two other inter-individual variability factors in drug response
- plasma protein binding
- body weight
metabolism is the irreversible loss of drug from the body by biochemical conversion
what two roles does it have in the pharmacokinetics of drugs?
- limits the life of a substance in the body
- promotes excretion and reduces the binding affinity
what 3 properties do metabolic reactions increase when metabolising a drug
- water solubility
- reactivity
- size
- Most metabolism occurs in the liver
- this is known as first-pass metabolisms and functions to reduce the bioavailability of a compound
first-pass metabolism is a two step process
Phase I and Phase II, what do these phases involve
- Phase I = oxidation, reduction, hydrolysis - creates a functional group
- Phase II = conjugation - polar group added to functional group
metabolism can often lead to the production of reactive metabolites, what is the impact of these?
- Inactive pro-drug converted to an active agent by metabolism
- Metabolite responsible for side effect profile
- Pharmacokinetic models allow the calculation of the appropriate dose and dosing interval
basic PK calculations are based on concentration-time curves using what measurement of area
AUC - area under curve
on a concentration-time curve,
what is the Cmax?
what is Tmax?
Cmax = the peak concentration of drug in plasma
Tmax = time at which the peak concentration occurred
what’s the difference between AUC and AUMC on a concentration-time curve
