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NURP 424 - Pharm Exam 1 Study Guide.
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NURP 424 - Pharm Exam 1 Study Guide.
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PHARMACOKINETICSBioavailability- F value- fraction of unchanged drug reaching systemic circulation. Greater in
meds that go straight into circulation like IV meds. 100% unchanged drug. Oral way less.
Factors that can affect bioavailability- drug formulations, how drug is transported across
the membrane, how it interacts with gastric acid & enzymes in GI tract, what binder were used.
Absorption- how blood gets into body. Rate at which drug leaves site of administration
and passes to systemic circulation
Factors that affect- blood flow to area of absorption sites, food, drug formulation, size
of molecule, whether its lipophilic or hydrophilic, cellular environment, is it passively going into
cell or need a signal transducing?
Lipophilicity- have an easier time getting through the cell wall. For a drug to be readily
absorbed it must be largely liphophilic yet have some solubility in aqueous solutions.
Mechanics of absorption-
Passive diffusion -Depends on difference in concentration. Strength of barrier and
distance of molecule needs to travel/ and particle size. Higher concentration to lower
concentration. Not charged not ionized easier
Facilitated diffusion- passive but uses a membraine protein to move polar charged
substances across membrane using transporter protein. No energy used.
Active transport- larger ionized molecules. Requires ATP to move substances across
cell membranes. Pump moves sodium ions out of cell and decreases amount of
potassium entering cell = allows substances to enter cell
Ionization- loss or gain of electrons. In clinical trials goal is to make drugs into either a
weak acid or weak base for effective absorption. Uncharged (easier to absorb) More basic (small
intestine absorption) More acidic (stomach absorption) LIKE DISSOLVES LIKE
First Pass Effect – reduces bioavailability of drug. Hits the stomach, and then has much less of the
drug available to systemic circulation. Need considerably higher dose. All done via clinical trials.
Distribution- where will drug go. Transport of drugs in body fluids from site of absopriton
to receptor site, maybe a storage site, and then to elimination site. Once drug absorbed must
reach its site of action to exert an effect.
, Volume of distribution- measure of apparent space in body available to contain the drug.
Theoretical process to predict concentrations, absorption and acculumaton. Extent of drug
movement out of blood into tissues or, stays in blood. Impacted by clearance.
3 compartments
Larger Vd- concentrates in tissues (liphophilic drugs) going to sit in your
body a little longer (Diazepam or valium)
Smaller Vd- concentrates in plasma (hydrophilic drugs) stays mainly in the blood (ex.
Warfarin)
Properties that affect distribution
Molecular size
Lipid solubility - lipophilic drugs distribute more easily into fats, hydrophilic distribute more
easily into extracellular spaces.
pH of environment- bases become nonionized in basic environments, vice versa.
Ionization-acidic drugs ionized & concentrated in blood. Basic drugs ionized in stomach
Acidic stays ionized in basic environments, Basic stays ionized in acidic environments
Nonionized cross cell membranes much more freely
Protein binding- major carrier protein is albumin. Drug that’s bound to the protein is inactive. Its actually
whats not bound to the protein that’s the active component of the drug. ONLY THE UNBOUND DRUG
CAN EXERT AN EFFECT. Important to look at drug to drug interactions for this reason.
Host related factors of distribution –
Nutrition status (lower protein, possibly more free drug available, might need to
reduce the dose, weight,
circulation ( if poor circulation, not distributed as well )
Renal failure or liver failure – possibility of toxicity b/c volume of distribution is increased due to
impaired plasma protein binding. More free drug available. Need to dose reduce. More lipophilic
drugs can pass the blood brain barrier easily, keep in mind for elderly patients with confusion.
Metabolism- how is it broken down? Chemically altered by enzyme into metabolites. If we
want the drug to get out of the body we want it to be more polar or more hydrophilic.
LIVER - Phase 1- oxidation, reduction, hydrolysis reactions- prepare drug for further metabolism/
make it more polar for excretion. Can make drugs more or less pharm activity, which occurs
when drugs interact with CYP450 system. Even more of a red flag to check
drug-drug interactions.
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