Lecture 1 part 3 Flashcards
is drug permeation a pharmacokinetic or dynamic principle
kinetic
drug permeation proceeds by how many mechanisms?
name them
4:
-aqueous diffusion
-lipid diffusion
-special carriers
-exocytosis and endocytosis
give an example of a molecule that needs a special carrier to permeate
glucose
true or false
passive diffusion in an aqueous or lipid medium is common
true
active processes play a role in the movement of drugs, especially with what kind of molecules —
those that are too large to diffuse readily
what is aqueous diffusion driven by?
usually by the concentration gradient of the drug
-downhill movement described by FICK’S LAW
Where does aqueous diffusion occur (3 places)
within larger aqueous compartments of the body
across epithelial tight membrane junctions
across the endothelial lining of blood vessels (through pores that permit 20,000-30,000 MW)
true or false
drug molecules that are bound to large plasma proteins like albumin will not permeate through aqueous pores
true
what is the most important RATE LIMITING FACTOR for drug permeation and why?
lipid permeation
bc there are a large number of lipid barriers that separate aqueous compartments of the body
what determines how readily the drug molecule moves between the aqueous and lipid media?
the lipid:aqueous partition coefficient
the higher the partition coefficient……..
the higher the lipid solubility
special carriers exist for what kind of substances?
that are important for cell function but too big or too insoluble in lipid to passively diffuse through membranes
-peptides
-amino acids
-glucose
how do these special carriers bring about movement
active transport or facilitated diffusion
special carrier transport mechanisms are ___ and ____
saturable and inhibitable
how is it that drugs can use special carriers used for endogenous substances like glucose, amino acids, and peptides, for their own transport?
because many drugs resemble these molecules
a few substances are so large that they can only enter cells how?
by endocytosis
define endocytosis
process in which the substance is engulfed by the cell membrane and carried into the cell by pinching off the newly formed vesicle inside the membrane
substance then released inside the cytosol bc of breakdown of vesicle membrane
endocytosis is responsible for the transport of what?
explain the transport mechanism
iron and vit B12
each forms a complex with binding proteins. they cross the wall of the gut and get into the blood
what is the reverse process of endocytosis? what is it responsible for?
exocytosis
the secretion of many substances from cells
give a specific example of exocytosis
many neurotransmitters are stored in membrane-bound VESICLES in nerve endings to protect them from metabolic destruction in cytoplasm.
therefore, only when the nerve ending is activated the storage vesicle fuses with the cell membrane and expulses the contents into the extracellular space
define Fick’s law and give the formula
passive flux of molecules DOWN a concentration gradient
flux = C1(higher conc)-C2 * [Area (where diffusion happening * permeability coefficient] / thickness of diffusion path
flux = number of molecules diffusing/unit time
in the case of _____ diffusion, the lipid: aqueous partition coefficient is a major determinant of the mobility of the drug.
why?
lipid diffusion
it determines how readily the drug enters the lipid membrane from the aqueous medium
true or false
the ionization of drugs reduces their ability to permeate through membranes
true
due to the electrostatic charge – attracts water dipoles and results in a polar, relatively water-soluble and lipid insoluble complex
true or false
a small fraction of drugs today are weak acids/bases
false - large fraction
what is the best buffer
the body
define a weak acid
acids that do not completely dissociate into their constituent ions when dissolved in solution
give 5 examples of weak acids
phosphoric acid
nitrous acid
methanoic acid
acetic acid
ascorbic acid
define a weak base
base that, when dissolves in water, does not dissociate completely. the resulting solution contains only small proportion of hydroxide ions
give 6 ex of weak base
ammonia (NH3)
aluminum hydroxide
lead hydroxide
ferric hydroxide
copper hydroxide
zinc hydroxide
what is the most important application of the principle of the ionization of weak acids/bases
the manipulation of drug excretion by the kidney
where are almost all drugs filtered?
the glomerulus
what will happen if a drug is too lipid-soluble when passing through the renal tubule
a significant fraction will be reabsorbed by simple passive diffusion back into the body
if the goal is to ACCELERATE the excretion of the drug, what is important?
how can it be accomplished?
prevent the reabsorption of the drug from the tubule and back into the body
can be done by adjusting the urine pH to make most of the drug ionized. The drug will be trapped in the urine
true or false
weak acids are usually excreted faster in acidic urine
false
alkaline
true or false
weak bases are usually excreted faster in acidic urine
true
in metabolism, lipophilic drugs are metabolized to form relatively more hydrophilic metabolites.
what can you say about these metabolites
they are more easily excreted (harder to be reabsorbed into the body)
true or false
lipophilic substances are harder to be reabsorbed than hydrophilic
false
hydrophilic are harder to be reabsorbed and more easily excreted from the kidney
