Lecture 2: Pharmokinetics Flashcards
Drugs can be bound to______. This happens generally via _____
blood proteins
electrostatic attraction
only ________ can distribute into tissues and interact with targets to have a pharmacodynamic effect
free, non bound drugs
conditions that affect ______ can affect the levels of free drug in the body
plasma protein levels such as hypoalbuminemia with chronic renal failure
the percent of drug that is ______ stays stable regardless of the concentration in the blood
protein bound
protein binding of less than ____ is not clinicaly very relevant
80%
what is the name of the drug that has a protein binding of more than 99% and slowly dissociates?
convenia (cefovecin)
metabolism is acheived via reactions that increase the _______ of a drug
water solubility/polarity
the main site of drug metabolism is the
liver
drug metabolism has 2 phases which are
redox and enzymatic
list some factors that can affect metabolism function and speed
age, health, and species
what is the name of the enzymes located in the liver that are found in intracellular organelles that increase the water solubility of drugs via an oxidation reaction?
cytochrome P450
upregulation of CYP enzyme familis results in ______
down regulation of CYP enzymes results in _____
loss of therapeutic effect because metabolism will increase
toxicity of the drug because it is not being metabolized enough
phase 2 of metabolism involved increasing water solubility by ________
conjugating the drug to exogenous substrates
what are the 3 most common conjugation reactions?
which species can do which ones?
glucuronidation (cats deficient)
sulfate conjugation (pigs not very good)
acetylation (dogs can’t)
the most important drug transport protein is _____, also known as ______
P-glycoprotein
multidrug resistance protein 1
P-glycoprotein is a _____ that moves substrates ____ of cells
effulx transporter
OUT
all drugs are filtered by the _____, EXCEPT FOR ____
glomerulus
protein bound drugs
some drugs can be eliminated without _____
prior metabolism
rate of renal excretion =
filtration + secretion - reabsorption
doses of drugs that are excreted by the kidney at least ___ unmetabolized should be reduced.
50%
what kind of molecules are likely to be excreted by the bile?
large molecules
what is enterohepatic recirculation?
what is the result?
when a drug is excreted into the small intestine with bile and it is then reabsorbed by the small intestine
result is prolonged drug exposure, double peaks on concentration vs time graphs
What is Cmax?
highest concentration achieved by a drug in the plasma
what is Tmax?
the time it takes to reach Cmax
what is the AUC?
area under curve, total drug exposure
what is the half life?
time it takes for the concentration of the drug in the plasma to decrease by half
doubling a dose of a drug extends by _____ the time it takes to reach a specific concentration
one half life
if a dosing interval is more than 5 half lives, then…
no drug will accumulate in the body and it will be fully cleared with each dose
the dose of the drug is decided by
the minimum effective concentration and the toxic concentration
the dose interval is decided by
the half life and clearance of the drug
what is steady state?
steady state is usually achieved after ____ half lives
when the amount of drug going into the body equals the amount leaving the body over the doing interval
5
what is a loading dose and why would you use it?
giving a single larger dose at the beginning of therapy. you would use this when you want to reach higher concentrations wuickly but the half life of the drug is very long. it is used to shorten the time to clinical effects of the drug
in general, withdral times are how many half lives?
10
drugs that are more _____ and less _____ are more easily passed across cell membranes
lipophilic, polar
what is bioavailability?
percentage of a drug that reaches the systemic circulation. IV drugs have a bioavailability of 100%
what is the first pass effect?
loss of a drug occurring by metabolism/degredation in the intestinal wall and liver during absorption
drugs with a high first pass effect have a _____ bioavailability
lower
when the pKa is lower than the pH of the environment, the _____ will predominate. Meaning what?
protonated
acids will be non ionized
bases will be ionized
when the pKa is higher than the pH of the environment, the ____ form will predominate. Which means what?
deprotonated
acids will be ionized
bases will be non ionized
Absorption of drugs that are acids will be better in an ____ environment, and drugs that are bases will be absorbed better in a _____ environment
acidic, like stomach
basic, like small intestine
meloxicam is an acid, pKa of 4.1. Will it be more absorbed in the atomach or the SI?
the stomach since it is more acidic
if you give a drug with a pKa of 8.8, will it be more or less ionized in the stomach?
stomach has a pH of 2, so this means the deprotonated form will predominate, meaning the acid will be more ionized in the stomach. it will therefore be better absorbed in the SI where it is more basic and nonionized
drugs tend to distribute into ____ compartments or ____
fluid, fat
a low Vd means
a high Vd means
the drug stays in ECF, outside cells
the drug stays inside cells
Vd can be very large if
a drug accumulates at a specific site outside the blood
what is ion trapping?
the side of the membrane favoring the ionized drug will tend to accumulate more drug than the side favoring the non ionized drug.
you have a drug that is a weak acid, pKa=3.4. Will the drug more likely be “ion trapped” in the stomach (pH 1.3) or the plasma (pH 7.4)?
in the stomach, the protonated form predominates meaning the acid is nonionized
in the plasma, the deprotonated form predominates meaning the acid is ionized
the non ionized drug will move across the membrane, but the ionized form will exist at a much greater concentration on the plasma side since it promotes ionization
you give an acidic drug with a pKa of 2.7 to a cow. Will the drug accumulate in the milk (pH 6.8) or the plasma (pH 7.4)?
the ionized form will predominate in both environments (deprotonated form since pH is higher than the pKa in both locations). But the pKa is further from the pH of the plasma compared to the milk. This means the drug will be more ionized in the plasma than in the milk. This means the total drug concentration will be higher in the milk compared to plasma since more NONionized drug would be in the milk.
an acid is more non ionized in an acid
a base is more non ionized in a base
