Pharmacokinetics Flashcards
Pharmacokinetics
the relationship between dose regiment and drug concentration
Pharmacodynamics
relationship between drug concentration and the theraputic/toxic effetcs
Pharmacokinetic Interactions
changes in outcome are the result of changes in relationship between the DOSE and the CONCENTRATION
the pharmacologic effect has changed as a result in a change in the drug concentrations
something is happening a the ADME level
Pharmacodynamic Interaction
changes in the OUTCOME are the result of changes in the relationship between the DRUG CONCENTRATION and EFFECT.
the pharmacological effect has changed despite lack of change in drug concentrtion
something is happening as the receptor level
Drug Absorption
process of drug moving from site of administration to systemic circ. (bypassed by IV administration)
Cell membranes
fxn as barriers to drugs
divide body into compartments
lipid-soluble=move freely across
not lipi-soluble=move less freely acorss
Bioavailability
amnt of drug that reaches systemic circ.
expressed as percent or frac. of drug administered which reaches the systemic circ.
AUC
area under curve: pharmacokinetic parameter which quantifies drug exposure
Absolute Bioavailability
situation when one of the AUC’s being compared is in a dose form with which there is 100% (absolute) absorption (with and IV dose form)
Relative AUC
comparing 2 dose forms in terms of relative amounts of drug that reaches systemic circulation
comparing AUC of 1 product RELATIVE to another
Bioavailability depends on
absorption characteristics of the drug & dose form
metabolism prior to drug reaching systemic circ (intestinal wall, liver, 1st pass effect)
presence of interacting substances (drugs/food)
Salt form differences
when changing from dose forms, have to consider differences in extent of absorption and amnt contained in the formulation
ex:salt forms have less than 100% of drug
Volume of Distribution (Vd) is higher in drugs with
HIGHER lipid solubility
lower protein binding
GREATER tissue binding
how would you use Vd to calculate the dose required to achieve target max. concentratipn (cpmax)
Cpmax=Dose/Vd
or
Dose=Cpmax x Vd
What can Vd be used for
determining drug doses
providing clinician w/sense of the spaces/areas/compartments into which drug distributes
Changes in fluid status would mostly likely affect a drug that has a
SMALL Vd (drugs are confined to the central compartment, so more or less fluid there will affect the response of the drug)
For a drug to be removed by dialysis, the Vd would be…
small Vd
the drug will stay in the central compartment (blood stream) so it will be removed by Hd
Two general mechanisms that eliminate drugs
Biotransformation (metabolism): drug chemically altered to form a “excretable” metabolite
Excretion: removal of a drug/metabolite from body via organ
Biotransformation
enzyme in organ modify chemical structure of drug (usually liver)
byproduct is metabolite
metabolite:less/no pharmacological activity (unless prodrug)
Mechanisms of Hepatic Biotransformation
Phase 1 & Phase 2
Phase 1 Reactions
introduce functional groups to prepare drugs for phase 2 rxns, occurs in LIVER
Oxidation-mediated by cytocrhome P450 (which are sensitive to induction/inhibition &aging/impairment of liver)-most common phase 1 rxn
Reduction-
Hydrolysis
Phase 2 Reactions
-drug/metabolite conjugated with glucuronic acid, methyl group, acetyl group, sulfate group
-rxns mediated by transferases (enzymes)
(transferases less sensitive to inhibiton/induction)
-produce less lipophilic (more polar) metabolite
more polar metabolite will stay in central compartment be excreted by kidney
Excretion
primarily kidney
Nephron-drug is filtered by glomaruluous, pass to renal tubule, and excreted in urine
if less polar, may be reabsorbed from tubule & re-enter systemic ciruc.
Drugs whos elimination processes are not easily maximized, elimination rate of the drug increases…..
in DIRECT proportion to the serum drug concentration concentration
would have linear pk
First order elimination
elimination rate of the drug increases in direct proportion to serum drug concentration
would have linear Pk
Drugs whos elimination process ARE easily maximized the elimination rate of the drug is…..
CONSTANT
Zero order Elimination
when the elimination of the drug is constant
once you max elimination of drug, the elimination rate doesnt change at higher concentration (the organ cant increase elimination and it stays constatn)
In Zero order elimination the serum drug concentration are…..
disproprtional to the dose administered.
would have non linear pk
once youre at theraputic level, change in dose causes BIG change in concentration
In Zero Order elimination, small increases in dose produce…
LARGE increases in serum drug concentration
In zero order elimination, the half life is…
DEPENDET of drug concentration
higher exposure=longer half life
In first order elimination, the half life is…
INDEPENDENT of drug concentration
half life is always the same
At Steady State, the rate of drug going into a pt…
is EQUAL to the rate of drug leaving the pt
At Steady State, the amount of drug eliminated over the dosing interval…..
is EQUAL to the dose admininstered over this time
What happens with regard to drug accumulation during steady state?
drug accumulation reaches EQUILIBRIUM
Factors that can cause a pt’s drug regime to be knocked out of steady state
anything that changes the input or out put
frequency of dosing, change in absorption, change in fluid volume, adding another drug, change in dose interval,
Primary determinate of how long it will take for a drug regime to reach steady state
the time to reach steady state is dependent on half life
drug w/longer half life will takw longer to reach steady state
drugs with shorter half lives will take less time to get to steady state
Drug Clearance
Volume of blood that is cleared of drug per/time
Elimination Half Life
Time it takes for the concentration of drug to be reduced by 1/2
How drug clearance & elimination 1/2 life have an effect on dosing regiment
A drug with a faster clearance or shorter elimination half life will probably need to be dosed more frequently, and vice versa
