Pharmacokinetics 2 Flashcards
In which circumstance is a drug MORE likely to pass through a lipid membrane?
a. a weak base where the pH of the solution is > the pKa of the drug
b. a weak base where the pH of the solution is < the pKa of the drug
c. a weak acid where the pH of the solution is < the pKa of the drug
d. a weak acid where the pH of the solution is > the pKa of the drug
A & C
Ionization describes the process where
a molecule gains a positive or negative charge; this affects a molecule’s ability to diffuse through lipid membranes
A drug’s pKa equals the pH where
50% of the drug is ionized and the other 50% of the drug is non-ionized
Ionization affects a drug’s
pharmacologic activity as well as its ability to pass through cell membranes
A drug that’s a weak acid will
donate a proton to water (pH = 7)
A drug that’s a weak base will
accept a proton from water (pH= 7)
An acid is a substance that
donates a proton
HA+ <–> H+ + A
A base is a substance that
accepts a proton
B- +H+ <–> BH
The pH measures the concentration of
hydrogen ions in an aqueous solution
If you put a strong acid or a strong base in water, it will
dissociate completely
If you put a weak acid or a weak base in water,
a fraction will ionize, and the remaining fraction will be non-ionized
Ionization is dependent on the following two factors:
the pH of the solution
the pKa of the drug
The pKa tells us how much
a molecule wants to behave like an acid
low pKa= amazing acid
high pKa= terrible acid
In an acidic solution, weak bases are
more ionized and water-soluble
In a basic solution, weak bases are
more non-ionized and lipid-soluble
In an acidic solution, weak acids are
more non-ionized and lipid-soluble
In a basic solution, weak acids are more
ionized and water-soluble
A weak acid is paired with a positive ion such as
sodium, calcium, or magnesium
A weak base is paired with a negative ion such as
chloride or sulfate
Describe the solubility of an ionized drug
water soluble- hydrophilic, liphophobic
Describe the diffusion of an ionized drug across lipid bilayers.
does not diffuse across blood-brain barrier, GI tract, and placenta
Does an ionized drug have an active or inactive pharmacologic effect?
not active
Describe hepatic biotransformation and renal elimination for an ionized drug.
hepatic biotransformation- less likely
renal elimination- more likely
Describe the solubility of a non-ionized drug.
lipid soluble
-liphophilic
-hydrophobic
Describe the pharmacologic effect on a non-ionized drug.
active
Describe the diffusion across lipid bilayers for a non-ionized drug.
diffuses across blood-brain barrier, GI tract, & placenta
Describe the hepatic biotransformation and renal elimination of a non-ionized drug.
hepatic biotransformation- more likely
renal elimination- less likely
Which circumstance creates the STRONGEST gradient for the passage of local anesthetic from the mother to the fetus?
a. maternal acidosis and fetal acidosis
b. maternal acidosis and fetal alkalosis
c. maternal alkalosis and fetal acidosis
d. maternal alkalosis and fetal alkalosis C.
C.- maternal alkalosis and fetal acidosis
Fetal pH is typically _____ than maternal pH
lower
Lower fetal pH can lead to
ion trapping and increased fetal drug concentrations
The combination of ________ & __________ worsens the problem of ion trapping in the fetus.
maternal alkalosis & fetal acidosis
Of the commonly used anesthetics for neuraxial anesthesia, _______ is most likely to undergo fetal ion trapping.
lidocaine
Of the commonly used anesthetics for neuraxial anesthesia, _________ is least likely to undergo fetal ion trapping.
chloroprocaine
If a drug is 98% bound by plasma protein, and the bound fraction decreases to 96%, the free fraction will increase by
100
Plasma proteins include
albumin, alpha 1-acid glycoprotein, and beta-globulin
Albumin primarily binds with
acidic drugs
Alpha 1-acid glycoprotein and beta-globulin typically bind with
basic drugs
These conditions can decrease protein concentrations
liver disease, renal disease, old age, malnutrition, and pregnancy
_______ synthesizes plasma proteins
The liver
A drug bound to a plasma protein cannot
bind to a receptor nor can it be cleared by a clearing organ
The extent of plasma protein binding affects the
intensity of drug effect effect and the drug’s duration of action
The most plentiful plasma protein is
albumin
Albumin is decreased by
liver disease
renal disease
old age
malnutrition
and pregnancy
Alpha 1 acid glycoprotein concentration is increased by
surgical stress
myocardial infarction
chronic pain
rheumatoid arthritis
advanced age
Alpha 1 acid glycoprotein concentration is decreased by
neonates
pregnancy
The percent increase formula is:
percent change= ((new value- old value)/old value)) x 100%
positive result= increase
negative result= decrease
Changes in protein binding can result from
decreased plasma protein content or competition for binding sites on the protein
Factors that decrease plasma protein include
reduced synthetic function (liver disease, malnutrition)
altered distribution (3rd trimester of pregnancy)
increased protein excretion (renal disease)
The volume of distribution is ______- related to the degree of plasma protein binding
inversely
Highly protein-bound drugs typically have a ______ rate of metabolism and elimination
slower
The risk of adverse effects is greatest when a drug has a
narrow therapeutic index
Alterations in plasma protein binding can be a problem in several situations such as during
CPB (hemodilution and heparinization) as well as in ECMO circuits
Which kinetic model describes the process that metabolizes a constant amount of drug per unit time?
a. zero order
b. first order
c. second order
d. third order
a. zero order
Describe zero order kinetics.
constant amount of the drug is metabolized per unit time
Describe first order kinetics.
constant fraction of the drug is metabolized per unit time
