Introduction to Pharmacokinetics Flashcards
4 stages of drugs
ADME absorption distribution metabolism elimination
absorption–3 times
dissolution
absorption
circulation
2 types of passive absorption
filtration
diffusion
dont require energy and cant proceed against gradients
passive filtration determined by?
osmotic/hydrostatic pressure differential
passive diffusion determined by?
concentration gradient
most commonly utilized by drugs
passive absorption also depends on?
ionization status
2 ionization forms of drugs in body
ionized and unionized
must add up 100%
ionized compound solubility
lower lipid solubility; higher water solubility
do not easily diffuse across lipid bilayer membranes
unionized compounds solubility
higher lipid solubility; lower water solubility
easily diffuse across lipid bilayer membranes
ionization status depends on 2 factors
pka of medication (propensity of a compound to donate protons)
pH of membrane gradient/milieu
2 important areas of body where pH varies and commonly impacts ionization status
GI tract
kidneys
when is there a 50/50 ratio of ionized to unionized?
when pka=ph
base drugs become more unionized when?
as ph goes up
acid drugs become more unionized whe?
when ph goes down
what happens to ionized drugs?
are eliminated
do not get absorbed in GI tract or reabsorbed in kidney
what happens to unionized drugs?
are NOT eliminated
readily get absorbed in GI tract or reabsorbed in kidney
active absorption/transport is associated with?
energy requiring
saturable (competitive inhibition by other drugs)
movement against gradients
facilitated diffusion is different from active transport how?
does NOT require energy
does NOT proceed against gradients
2 stages for drugs related to serum protein binding
bound
unbound (active)
alpha represents what?
unbound fraction
small alpha=smaller unbound
alpha is opposite of % protein bound
What happens when there is low protein binding with low displacement? (30% bound; 70% free–>10% competition)
3% absolute change yet 4.3 % relative change
high protein binding with low displacement–what happens (98% bound; 2% free–>10% competition)
10% absolute change yet 500% relative change
what does metabolism do?
increases likelihood of drug elimination from body
alteration of drug to 1 or more chemically diff compounds (metabolites) which are pharmacologically active or inactive
Are metabolites more or less active than the parent compound?
can be either more or less active
2 main types of biotransformation reactions used by body
phase 1 and phase 2
What are phase 1 reactions?
formation of new or modified functional group or cleavage (oxidation, reduction, hydrolysis)
CYP 450
Phase 2 reaction
conjugation (covalent linkages–glucuronidation, sulfation, acetylation) with an endogenous substance (glucuronic acid, sulfate, glycine)
CYP450 naming
family–numbers
subfamily–capital letter
individual–numbers
ex: 2C19
CYP 450 main sites of actin
liver
GI tract
brain
kidney
CYP 450 different drug types
substrate needs CYP 450 to be metabolized
inducers–induces CYP 450 system
inhibitors–inhibits CYP 450 system
first pass metabolism/effect what is it?
orally administered drugs that go straight to liver (gets chewed up to be inactive)
routes of elimination
liver and kidneys are primary
lungs
skin
bile/feces
elimination of parent drug vs metabolite
active vs inactive
ionization status
elimination–what can necissitate a dosing change?
reduced renal or hepatic function
3 main processes of renal elimination
passive glomerular filtration (blood flow dependent)
passive tubular diffusion (passive or distal tubules–ionization and conc status dependent)
active tubular secretion (weak acids/bases secred into proximal tubules
