Quantitative Aspects of Drug Action Flashcards
Drug definition
A chemical compound that when applied to a biological system alters its function in a specific manner
affinity definition
chemical forces involved in the association of a drug with the receptor. Determine occupation
efficacy definition
ability of a drug to activate the receptor and produce a response. Determines activation
agonist definition
molecule that binds to receptor and produces a response
antagonist definition
molecule that binds with high affinity but zero efficacy
therapeutic window definition
a range of doses that produce a therapeutic response without causing significant adverse effect in patients
what is above the therapeutic window + below?
above- side effects
below- sub-therapeutic
therapeutic index definition
Ratio between the minimum effective concentration and the minimum toxic concentration
EC50 definition
the minimum effective dose for 50% of the population
LD50 definition
the lethal dose of a drug for 50% of the population
four main processes of pharmokinetics when a drug is taken +
ADME
Absorption- process of drug entering the systemic circulation
Distribution- movement from body fluids to organs/compartments
Metabolism- breakdown of drugs
Excretion- removal of drugs
different factors that affect absorption
charge, lipophilicity, size
why is lipid solubility important?
need to diffuse through lipid bilayer of epithelia to enter circulation
are drugs generally acidic or basic + why is this important?
generally weak acids and bases so equilibrium is weighted towards non-ionised forms at 7.4 pH
pKa definition
the pH were the drug exists as 50% ionised and 50% unionised
where are acidic drugs absorbed? why?
stomach, were the pH is 3 so less likely to become ionised
where are basic drugs absorbed + why?
small intestine, where the pH is 9 so less likely to become ionised
partition coefficient definition
measure of the relative solubility of a compound in aqueous and lipid environments, critical determinant of drug absorption
ratio of lipid solubility to aqueous solubilty
what does a high partition coefficient mean? + what can it lead to?
more membrane soluble
some drugs remain trapped in body fat
distribution definition
how drugs equilibrate after entering the body
at equilibrium what can be said about the distribution of the drug?
concentration of the nonionised molecules is the same in each compartment
there is more drug in larger body compartments
volume of distribution definition
the volume of fluid required to contain the total amount of drug in the body at the same concentration as that is present in the plasma
volume of distribution formula
dose/plasma concentration
what does the volume of distribution represent?
the degree to which a drug is distributed in body tissue rather than plasma
what does a higher Vd mean?
greater amount of tissue distribution
plasma protein effect
bind to free drugs
reduce their ability to diffuse into tissue fluid, reducing renal clearance of drugs
where does drug metabolism mainly take place?
liver
two phases of metabolism + briefly processes that occur
phase 1- oxidation and reduction, hydrolysis
phase 2- conjugation using glycine, glutathione, methylation, acetylation, sulfation
clearance definition
volume of plasma that is cleared of drug per unit of time
does not say how much drug is cleared, as this depends on volume of distribution
clearance equation
rate of elimination/plasma concentration
what does chemical modification do to the drug?
inactivates it
half life definition
the period of time required for the concentration or amount of a drug in the body to be reduced by half
what does a drug’s plasma half life depend on?
how quickly it is excreted or translocated to another compartment of destroyed
governed by clearance and distribution
elimination is first order, what does this mean?
the time taken for half the drug to be eliminated is constant
what is done to maintain prolonged therapeutic activity?
repeated oral dose regimens
what does the time profile for repeated oral dose regimens look like?
concentration of drug drops after each dose but no longer drops as far as it did before
eventually begins to plateau
time profile for continuous intravenous infusion described
drug is infuesed for a long period of time at a constant rate
concentrations increase until they approach a constant concentration
this is where the rate of elimination is equal to the infusion rate
why must drugs be metabolised?
need to be made polar so they can be excreted from the body (prevents reabsorption)
where may drugs be uptaken? + found in main two excrements
gut
bile and urine
renal effect
lipid solubility and pKa can effect excretion at the kidneys
if the urine is acidic/alkaline the drugs may become non ionised or ionised and thus reabsorbed or excreted
