4&5- Pharmacokinetics Flashcards
drug delivery via the GI tract
enteral administration
drug delivery via a route that does not involve the GI tract. requires piercing the skin
parenteral administration
advantage of sublingual and buccal over oral administration
sublingual and buccal enter the venous system and therefore bypass 1st exposure
administration via an injection into the subarachnoid space for delivery of drugs into the CNS
intrathecal administration
the ________ form is readily able to cross lipid membranes
non-ionized form
the non-ionized form of a WA =
protonated WA (aka HA)
the non-ionized form of a WB =
unprotonated WB (aka B)
where are weak acids better absorbed- stomach or intestine?
stomach
where are weak bases better absorbed- stomach or intestine?
intestine
when pH
protonated form will predominate if the pH is less than the pKa
increase cardiac output = _________ distribution
increase
increase regional blood flow = _________ distribution
increase
increase capillary permeability = __________ ddistribution
increase
increase binding to plasma proteins = _________ distribution
decrease ***
*important
increase drug molecule size = _____ distribution
decrease
increase lipid solubility of drug = ______ distribution
increase
goal of biotransformation
make the molecule more water soluble (more polar) for eventual excretion
prodrug
makes use of biotransformation to activate the drug
oxidative
reductive
hydrolytic
phase 1 biotransformation
cytochrome P450 enzymes
phase 1 biotransformation
glucoronidation
sulfation
acetylation
phase 2 biotransformation
conjugation
phase 2 biotransformation
first pass effect
large percentage of a drug absorbed by stomach or intestine will be carried to the liver by the portal vein and exposed to metabolism before entering circulation –> drug can be inactivated before reaching target
primary mechanism of drug elimination
renal excretion
increase GFR = ________ filtration
increase
increase binding to plasma prtns = ________ filtration
decrease
V =
volume of distribution
measure of space in body available to contain the drug
C =
concentration of drug in blood
a low volume of distribution indicates…
most of the drug stays in the blood circulation
a higher V would indicate that the drug is highly distributed throughout the body or concentrating somewhere
CL=
clearance
rate of elimination in relation to drug concentration
capacity of drug removal by organs
clearance that is independent of drug concentration
zero order elimination
concentration of drug has saturate the elimination capacity of the system and mimics zero order kinetics
capacity limited elimination
if dosing rate > elimination rate, the concentration will continue to _________ in blood
increase
dangerous for toxic effects
constant fraction of drug is eliminated
first order elimination
the greater the flow the _______ rate of elimination
greater
kinetics of flow-limited elimination mimic first order elimination
rate of elimination
rate of elimination = k
k = 0.693/ t.5
accumulation of a drug in the body will be detectable if the dosing interval is shorter than ______ half lives
4
amount of drug that reaches systemic circulation
bioavailability
ER =
extraction ratio
Q =
hepatic blood flow (usually 90)
F =
bioavailability
f =
extent of absorption (gut)
TC =
target concentration
what is the therapeutic window?
concentration range between MEC for desired effects and MEC for toxic effects
Css =
steady state concentration
point during a dosing regimen when elimination of a drug is equal to bioavailability of drug
should be within the therapeutic window
you will always reach the Css within ____ half lives
4
the time it takes to reach Css is _________ of dose or dosing rate but is ___________ upon the half-life
independent
dependent
dose needed to maintain steady state concentrations
maintenance dose
why is decreasing the dosing rate potentially problematic?
this will increase the dosing interval and the peak and trough may excede the therapeutic interval with a larger maintenance dose
LD =
loading dose
initial dose that can be given in order to achieve the target concentration rapidly
