introduction to pharmacokinetics 1 Flashcards
what does there need to be for a drug to exert an effective pharmacological effect?
adequate drug concentration at the target tissue
drug disposition
process by which a pharmaceutical compound (drug) is absorbed, distributed, metabolized, and excreted within an organism, typically a human or an animal
pharmacokinetics
what the body does to the drug
pharmacodynamics
what the drug does to the body
by what model can drug disposition be described
the ADME model
what does ADME stand for
Absorption
Distribution
Metabolism
Elimination
how do you define the boundary of what is inside or outside of the body?
The epithelial cell layer defines the boundary of the body
E.g. Digestive and respiratory systems classed as outside the body
A substance is considered Inside the body when the substance has crossed the epithelial barrier into the bloodstream
How many different routes of drug administration can youth think of?(name at least 5)
intravitreal
intranasal
intramuscular
transdermal
subcutaneous
transmucosal
intrathecal
epidural
rectal
viginal
and many more…..
how do the intestinal walls and the liver serve as barriers?
the intestinal walls and the liver function as the protective barrier to prevent the entry of xenobiotics into the body
xenobiotics
foreign substances or chemical compounds that are not naturally produced or expected to be present in an organism’s body
formula for bioavailability
Bioavailability (F)= fraction absorbed (fg) * fraction escaping first-pass metabolism (fH)
describe the “first-pass effect”
The extent at which a drug is removed by the liver during the first passage into the portal vein through the liver (fraction of dose escaping first-pass effect (fH))
read the following if you want to understand more(it is from chatgpt)
refers to the phenomenon that occurs when a drug is administered orally (by mouth) and is absorbed from the gastrointestinal tract, it enters the hepatic portal circulation (the network of blood vessels that carries blood from the digestive organs to the liver) before entering the systemic circulation (the bloodstream that circulates throughout the body). During this process, the drug is exposed to the liver’s metabolic enzymes before it reaches the systemic circulation. As a result, some drugs are extensively metabolized or transformed by the liver before they can exert their therapeutic effects in other parts of the body.
which organ is the first pass effect primarily linked to
the liver
what is the bioavailability of an intravenous dose
1 or 100%
to measure the bioavailability of a plasma drug on a concentration-time graph, what formula do we use
AUCoral/ AUCintravenous
what is bioavailability
The fraction of the drug that reaches systemic circulation as an intact drug
absorption of drugs in terms of bioavailability
Extent intact drug is absorbed from the gut lumen into the portal vein (fraction dose absorbed from gut (fg))
cell membranes
the barriers between compartments in the body
what does cholesterol affect in cell membranes?
the fluidity and stability of the membrane
how do lipophilic molecules cross the cell membrane
they permeate the cell membrane, i.e, they diffuse straight through the lipid bilayer
the permeability of lipid molecules through the cell membrane is dependent on?
the concentration gradient of the molecule
partition coefficient
solubility in lipids is measured by?
the partition coefficient(Log P)
in what phase do lipophilic drugs partition
in what phase do hydrophilic drugs partition
the hydrophobic phase
aqueous phase
formula for the partition coefficient
log drug(in the hydrophobic phase)/ log drug (in the aqueous phase)
if a drug has a high partition coefficient, then what does that say about it’s lipophilicity and permeability
it means that it has a high lipophilicity and permeability
partition coefficient
refers to the ratio of drug concentration in each phase(i.e the lipophilic and aqueous phase)
match these log P values and their formulations(the formulations have to kinda come from memory icl)
0
0-3
3-4
4-7
injectable
oral
transdermal
toxic(fatty tissues)
factors that affect the bioavailability of drugs
solubility
instability(for example proteases breaking down insulin in the stomach, if taken orally)
first pass effect
factors that affect the absorption
pH
P-glycoprotein
total surface area and contact time
blood flow
pka
the pH where ionised and unionised forms of the weak acid or base are equal
in an acidic environment the unionised form of a weak base predominates, and an ionised form of the weak acid predominates, true or false
false. in an acidic environment, the ionised form of a weak base predominates, and an unionised form of the weak acid predominates
in a basic environment, which forms of a weak acid and a weak base predominate?
ionised form of the weak acid predominates and an unionised form of the weak base predominates
distribution
refers to the movement of drug molecules from the circulating blood to other areas of the body
when is the distribution equilibrium achieved
when the rate of drug entering a tissue/ organ is equal to the rate of removal of drug from a tissue/ organ
what is drug distribution rate dependent on
Blood flow
Concentration gradient
Permeability of cell membranes between compartments (absorption (Log P, pKa)
Drug binding to plasma proteins or tissue components
drug-protein binding
The readily reversible interactions of drugs with proteins
in the drug plasma, what can drugs bind to
Proteins in the plasma Tissue components
RBCs
albumin mainly binds drugs with what range of pH
an acidic pH
so from 0-6
can albumin bind to basic drugs sometimes?
yes
what are the two well-characterized primary high-affinity binding sites of albumin
sudlow site I and sudlow site II
what is site I of albumin also referred to as
warfarin site, because it is where the drug warfarin binds. many other drugs with complementary structural features can also bind to it
what is the site II of albumin also known as
the benzodiazepine site
volume of distribution
Relates the total amount of drug in the body to the concentration of drug in the plasma
what is assumed when calculating the volume of distribution of a drug
we assume that the distribution equilibrium has been achieved
formular for the volume of distribution of a drug
total amount of drug in the body(mg)/ plasma drug concentration (mgL^-1)
purpose of the volume of distribution
used to calculate what dose should be administered to achieve the therapeutic drug plasma concentration
what is the average volume of plasma in humans
2.7L- 3.0L
