ADME tutorials Flashcards
Percentage of drugs that fail in clinical trials due to ADME
10%
Route with most rapid onset
intravenous
Morphine is a metabolite of codeine and this metabolite is responsible for the
analgesic effect when codeine is administered. In a patient who has a genetic
defect such that they cannot metabolize codeine, the magnitude of pain relief
would be expect to be _____________ compared to normal patients
Decreased
Slowing gastric emptying would be expected to have what effect on the absorption
of a drug absorbed by passive diffusion?
It will take longer to achieve peak concentration
Which mechanisms move drug down a concentration gradient?
Paracellular, transcellular, facilitated diffusion
Which mechanism goes against concentration gradient?
Active transport
Co-administration of an inhibitor of the efflux protein p-glycoprotein (pgp) would be
expected to have what effect on the oral absorption of a drug that is a substrate
for pgp?
Increase amount of drug absorbed
Which of the following modifications would be not expected to increase the
transcellular permeability of a drug molecule?
Removing ionized groups
Decreasing lipophilicity
reducing molecular size
Decreasing lipophilicity
A drug that is only distributed into vascular space will exhibit a monoexponential
blood concentration versus time curve after intravenous administration. True or
False?
False
Which of the following drugs is most likely to undergo transvascular transport via
convection?
a. Aspirin (MW 180 g/mole)
b. Cimetidine (MW 252 g/mole)
c. Vancomycin (MW 143 g/mole)
d. Idarucizumab (MW 47,766 Daltons)
Idarucizumab
A decrease in the plasma protein binding of a drug would be expected to have
what effect on the distribution of drug into tissue?
Increase amount of drug in tissue
A change in the structure of a drug molecule such that it is no longer transported
by pgp (MDR1) would be expected to have what effect on the CNS concentration
of drug compared to the original drug?
The new drug would have a higher concentration in the CNS
Which of the following renal excretory processes for drugs is most likely subject to
competitive drug-drug interactions?
tubular secretion
In examining the renal elimination of a series of chemically related compounds, as
molecular weight increases, the extent of filtration will ______________
Decrease
%in bile vs mw plot relationship
direct
What is the effect of enterohepatic recirculation (EHR) on the half-life of a drug?
Increases the half life
For a drug that is eliminated solely by glomerular filtration, a decrease in plasma
protein binding will result in a(n) ____________ in the renal elimination of the drug
Increase
Which of the following undergoes bioactivation in the kidney?
Vitamin D
Which pathway of metabolism is most likely to result in a significant increase in the
molecular weight of a drug?
Phase II
Which pathway of metabolism is most likely to result in a metabolite eliminated in
the bile?
Phase II
Which type of inhibitor of CYP450 would produce the longest lasting inhibition?
Mechanism base inhibition
In general, inducers of CYP450 are selective for one specific enzyme or enzyme
family
False
The fate of a drug once it enters the systemic circulation.
Disposition
The study of the absorption, distribution, biotransformation, and
elimination of xenobiotics.
Pharmacokinetics
The study of the molecular, biochemical, and physiological effects
of xenobiotics and their mechanisms of actions.
Pharmacodynamics
A chemical that is normally foreign to the body. This includes drugs,
occupational chemicals, environmental compounds, etc.
Xenobiotics
The passive movement of drug through lipid membranes. This
movement is driven by concentration gradient
Transcellular diffusion
The passive movement of drug between cells via tight junctions.
This movement is driven by concentration gradient.
Paracellular diffusion
A carrier-mediated process that involves a transport protein which
moves drug with a concentration gradient.
Facilitated diffusion
A carrier-mediated process that requires energy and can move drug
against a concentration gradient
Active transport
A process by which a cell engulfs and internalized a particle
Endocytosis
The movement of drug molecules across biological membranes into various
tissues in the body.
Distribution
The movement of drug molecules cross vascular endothelial
cells and into tissue interstitial space
Transvascular transport
A transvascular transport process that is driven by pressure.
Convection
A transvascular transport process that is driven by a concentration gradient.
Diffusion
The concentration of drug within a tissue due to pH differences that lead
to ionization of the drug in the tissue environment
Drug trapping
The initial movement of drug from highly perfused tissues to poorly
perfused tissues
Redistribution
Biotransformation of xenobiotics (a compound foreign to the body)
that includes oxidation, hydroxylation, and related changes that either introduce or expose
a functional group
Phase i Metabolism
Biotransformation of xenobiotics that involves conjugation with a
polar group (e.g., sulfate, glucuronic acid) yielding a polar metabolite that can be more
readily excreted in the bile or urine. These pathways are sometimes referred to as
conjugation reactions and can be influenced by the availability of the co-substrate (e.g.,
sulfate or activated sulfate).
Phase II Metabolism
The active transport of drug from blood into the renal tubule,
occurring primarily in the proximal tubule.
Active tubular secretion
The movement of solute from inside the renal tubule back into
the blood. This is primarily a passive process for drugs and is driven by the high
concentration effect that occurs as a result of the large fraction of filtrate that is
reabsorbed
Tubular reabsorption
The reabsorption of drug from the small intestine after drug
has been excreted through the bile into the intestine.
Enterohepatic recirculation
The process by which food stimulates release of bile, and drug contained
therein, into the small intestine, followed by reabsorption of the drug. This occurs because
release of bile into the small intestine in man is periodic, allowing drug to accumulate in
the gall bladder
Dose dumping
