Lecture 2 Flashcards
Formula for determining bioavailability
Concentration after gastric absorption
—————————————————
Total dose
The fraction of an administered drug that reaches the systemic circulation is ______.
Bioavailability
Drugs given IV have ___% bioavailability.
100
First pass hepatic elimination occurs via the _______.
Portal circulation
The liver can metabolize or excrete drugs via _____ and thus limiting their bioavailability.
Bile
Drugs with a high first-pass metabolism must be given in _____ doses parenterally.
Higher
Drugs that are too _____ may be poorly absorbed.
Lipophilic
Drugs that are too _____ have difficulty passing through the cell membranes.
Hydrophilic
The most commonly administered drugs are either weakly alkaline or weakly acidic due to the ______ characteristics of the drug.
Solubility
Why is insulin using given SQ and not PO?
It is chemically unstable in the GI tract
What 3 factors affect bioavailability?
Solubility characteristics of the drug
Chemical stability in the GI tract
Drug formulation
Rectal has a ____ first past effect than oral.
Smaller
Transdermal route usually has very ____ absorption, but it is used due to _____.
Slow
Lack of first-pass effect
Drugs that are mostly confined to the intravascular space (such as gentamicin or mannitol) have a _____ volume of distribution.
Smaller
After absorption, drugs must be ______ throughout the body.
Distributed
When there is less _____ in the blood to bind with, there is more free drug in the serum to bind to the receptor and become active.
Protein
Drugs that have an ______ appear to have a large volume of distribution.
Extensive distribution outside the plasma
Distribution is usually accomplished through _______.
Circulation via the blood stream.
What 3 things are distribution mostly dependent on?
Blood flow
Fat/water solubility
Protein binding
90 percent of steady state drug concentration is achieved in _____t1/2.
3.3
_____ occurs when a portion of the drug is bound to the proteins in the blood and therefore is not able to be free to bind to an active site and produce an effect.
Protein binding
Protein binding occurs when a portion of the drug is bound to the proteins in the blood and therefore is not able to _______________.
Be free to bind to an active site and produce an effect.
50 percent of steady state drug concentration is achieved in _____t1/2.
1
Only the _______ is available to bind with the receptor site.
Free drug not bound to the protein
Drugs that have extensive distribution outside the plasma (such as digoxin, diltiazem, labetalol, meperidine, or nortriptyline) appear to have a _____ volume of distribution.
Large
Low protein in plasma = _______ free drug
Greater
What happens if a second Drug B were in the blood stream in addition to protein-bound Drug A?
Drug B would compete and displace Drug A causing an increase in availability and effect of Drug A
The major determinant of hemp filtration is typically the amount of ______.
Protein binding
_______ are not well correlated with molecular weight.
Sieving coefficients
What are the 5 main ways your patients will eliminate drugs?
Urine Bile Hepatic metabolism Lung/oxygenator expiration Artificial filtration
______ is the time required for the concentration or amount of drug in the body to be reduced by one-half.
Half-life
_____ percent of steady state drug concentration is achieved in t1/2.
50
______ can be thought of as the volume of fluid that is required to contain an entire drug in the body at the same concentration measured in a given compartment.
Volume of distribution
Loading doses are particularly important with drugs that have _____.
Long half-lives
The half-life assumption assumes _______.
First order kinetics
First Order Kinetics means a ______ of the drug is metabolized per unit time.
Constant proportion
_____ percent of steady state drug concentration is achieved in 3.3t1/2.
90
How do you calculate clearance?
Clearance = (.693 x Vd) / (T1/2)
Some drugs are administered in such high doasages that they are eliminated by a constant amount over time because they’ve overwhelmed clearance mechanisms are called ______.
Zero-order kinetics
Repeated dosing of a drug won’t allow for the drug to accumulate in the body unless the dosing interval is ________.
Less than 4T1/2
________ of drugs into more polar molecules makes them less protein-bound at physiological pH and thus more readily filtered.
Biotransformation
Accumulation of a drug is necessary in order for the drug to reach a _____ in the plasma.
Steady state
Induced P450 enzymes metabolize drugs ______.
Faster
What directions do half-lives work?
Reaching a steady state
Elimination
What factors affect clearance?
Volume distribution
Half life
Kidney and liver function
Drugs that are mostly ________ space have a smaller volume of distribution.
Confined to intravascular space
What factors affect accumulation?
Method and frequency of dosing
Bioavailability
____ is the drug concentration that will produce the desired therapeutic effect?
Target concentration
Inhibited P450 enzymes metabolize drugs _____.
Slower
The liver(and the GI tract to a much lesser degree) extensively by a transform struggle through its _____. complexes
Cytochrome P450
Loading dose calculation
(Vd X target plasma concentration) / bioavailability
What can be done if there is not enough time to wait for multiple half-lived to pass to approach a steady-steady of drug accumulation?
You can give a bigger loading dose
______ P450 enzymes metabolize drugs slower.
Inhibited
_________ can turn non-biologically active drugs into active drugs or convert drugs into even more active forms.
Biotransformation
Formula for volume of distribution (Vd)
D/C^0
Amount of drug in body (dose) —————————————————————————— Concentration of drug in given compartment at time zero
Cytochrome P450 Complexes are a large family of _____ with the enormous genetic variation.
Heme-containing enzymes
______ are generally the same doses given at regular intervals.
Maintenance doses
Maintenance dose formulas
Dosing rate X dosing interval
(Clearance X target plasma concentration) / bioavailability
_____ is the rate of drug metabolism and elimination is directly proportional to the concentration of free drug.
First order kinetics
______ P450 enzymes metabolize drugs faster.
Induced
________ administration of a drug results in oscillations in plasma concentrations that are influenced by both by both the rate of drug absorption and elimination.
Repeated fixed dose
Phase ___ Biotransformation conjugates the drug with another chemical.
2
A _____ dose given orally results in a single peak in plasma concentration followed by a continuous decline in drug level.
Single fixed dose
The plasma concentrations during oral therapy fluctuate around the steady-state levels attained with ______.
Intravenous therapy
When dosages are doubled, halved, are stopped during steady-state administration, the time required to achieve a new steady-state level is ____________________.
Independent of the route administration
Where does the majority of biotransformation occur?
Liver
Some drugs/chemicals make the Cytochrome P450 system more active by increasing the rate of synthesis are decreasing the rate of the degradation, which is called ______.
Induction
______ are a large family of heme-containing enzymes with the enormous genetic variation.
Cytochrome P450 Complexes
Noncompetitive antagonist reduce agonist _____.
Efficacy (decrease Emax)
________ can shorten the drugs biological half-life.
Biotransformation
Phase ____ Biotransformation metabolizes the drug into a more polar form.
1
What effect does biotransformation of a drug into a polar molecule?
Can greatly decrease activity and half-life
Many lipophilic drugs are tightly bound to protein and thus unavailable for excretion by the _______.
Kidneys
The drug receptor complex initiate alterations in biochemical and or molecular activity of a cell by a process called _____.
Signal transduction
The phenomenon of desensitizing is called _______.
Tachyphylaxis
During the recovery phase, unresponsive receptors are said to be ____.
Refactory
____ of receptors can make the cells more sensitive to agonist and/or more resistant to the effect of the antagonist.
Up-regulation
______ is a measure of the amount of drug necessary to produce an effect of a given magnitude.
Potency
______ is the magnitude of response I drug causes when it interacts with the receptor.
Efficacy
What does efficacy depend on?
The number of drug-receptor complexes formed
Intrinsic activity of the drug
______ antagonist reduce agonist efficacy (____ Emax).
Noncompetitive
Decrease
_______ is the drugs ability to activate the receptor and cause a cellular response.
Intrinsic activity
What does maximum efficacy assume?
That all receptors are occupied by the drug, and no increase in response is observed if a higher concentration of drug is obtained.
The ______ of a drug determines its ability to fully or partially activate the receptors.
Intrinsic activity
And agonist binds to a receptor it and produces a _____ based on the concentration of the agonist and the fraction activated receptors.
Biological response
What is the value of the intrinsic activity for partial agonist?
Greater than zero but less than one
This type of at antagonist binds to a site other than the agonist binding site and prevents the receptor for being activated by its agonist.
Allosteric
_____ have an intrinsic activity less than zero, reverse the activity of receptors, and exert the opposite pharmacological effect of agonists.
Inverse agonist
Competitive antagonist reduce agonist ______.
Potency (increase EC50)
Which antagonist are considered non-competitive?
Irreversible
Allosteric
_____ bind to a receptor with high affinity but possess zero intrinsic activity.
Antagonist
An antagonist has no affect in the absence of an _____.
Agonist
If both the antagonist in the agonist bind to the same site of the receptor in a reversible manner, they are said to be _____.
Competitive
What does a competitive antagonist do?
Prevents the agonist from binding to its receptor which leaves the receptor in its in active state.
_____ antagonist bind covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist.
Irreversible
And Allosteric antagonist causes _____ shift of the Emax, with _____ shift of the EC50 values of agonist.
Downward
No
______ antagonist reduce agonist potency (____ EC50).
Competitive
Increase
An Irreversible antagonist causes _____ shift of the Emax, with _____ shift of the EC50 values (unless spare receptors are present).
Downward
No
This antagonist acts at a completely separate receptor, initiating effects that are functionally opposite those of the agonist
Functional antagonist
What does the larger therapeutic index mean?
There is a wide margin between doses that are effective in doses that are toxic.
Agents with low therapeutic index, which the dose is critically important, are those drugs for which ____ critically alters the therapeutic effects.
Bioavailability
