Lecture 2

Question 0

Formula for determining bioavailability

Answer 0

Concentration after gastric absorption
—————————————————
Total dose

Question 1

The fraction of an administered drug that reaches the systemic circulation is ______.

Answer 1

Bioavailability

Question 2

Drugs given IV have ___% bioavailability.

Answer 2

100

Question 3

First pass hepatic elimination occurs via the _______.

Answer 3

Portal circulation

Question 4

The liver can metabolize or excrete drugs via _____ and thus limiting their bioavailability.

Answer 4

Bile

Question 5

Drugs with a high first-pass metabolism must be given in _____ doses parenterally.

Answer 5

Higher

Question 6

Drugs that are too _____ may be poorly absorbed.

Answer 6

Lipophilic

Question 7

Drugs that are too _____ have difficulty passing through the cell membranes.

Answer 7

Hydrophilic

Question 8

The most commonly administered drugs are either weakly alkaline or weakly acidic due to the ______ characteristics of the drug.

Answer 8

Solubility

Question 9

Why is insulin using given SQ and not PO?

Answer 9

It is chemically unstable in the GI tract

Question 10

What 3 factors affect bioavailability?

Answer 10

Solubility characteristics of the drug
Chemical stability in the GI tract
Drug formulation

Question 11

Rectal has a ____ first past effect than oral.

Answer 11

Smaller

Question 12

Transdermal route usually has very ____ absorption, but it is used due to _____.

Answer 12

Slow

Lack of first-pass effect

Question 13

Drugs that are mostly confined to the intravascular space (such as gentamicin or mannitol) have a _____ volume of distribution.

Answer 13

Smaller

Question 14

After absorption, drugs must be ______ throughout the body.

Answer 14

Distributed

Question 15

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.

Answer 15

Protein

Question 16

Drugs that have an ______ appear to have a large volume of distribution.

Answer 16

Extensive distribution outside the plasma

Question 17

Distribution is usually accomplished through _______.

Answer 17

Circulation via the blood stream.

Question 18

What 3 things are distribution mostly dependent on?

Answer 18

Blood flow
Fat/water solubility
Protein binding

Question 19

90 percent of steady state drug concentration is achieved in _____t1/2.

Answer 19

3.3

Question 20

_____ 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.

Answer 20

Protein binding

Question 21

Protein binding occurs when a portion of the drug is bound to the proteins in the blood and therefore is not able to _______________.

Answer 21

Be free to bind to an active site and produce an effect.

Question 22

50 percent of steady state drug concentration is achieved in _____t1/2.

Answer 22

1

Question 23

Only the _______ is available to bind with the receptor site.

Answer 23

Free drug not bound to the protein

Question 24

Drugs that have extensive distribution outside the plasma (such as digoxin, diltiazem, labetalol, meperidine, or nortriptyline) appear to have a _____ volume of distribution.

Answer 24

Large

Question 25

Low protein in plasma = _______ free drug

Answer 25

Greater

Question 26

What happens if a second Drug B were in the blood stream in addition to protein-bound Drug A?

Answer 26

Drug B would compete and displace Drug A causing an increase in availability and effect of Drug A

Question 27

The major determinant of hemp filtration is typically the amount of ______.

Answer 27

Protein binding

Question 28

_______ are not well correlated with molecular weight.

Answer 28

Sieving coefficients

Question 29

What are the 5 main ways your patients will eliminate drugs?

Answer 29

``` Urine Bile Hepatic metabolism Lung/oxygenator expiration Artificial filtration ```

Question 30

______ is the time required for the concentration or amount of drug in the body to be reduced by one-half.

Answer 30

Half-life

Question 31

_____ percent of steady state drug concentration is achieved in t1/2.

Answer 31

50

Question 32

______ 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.

Answer 32

Volume of distribution

Question 33

Loading doses are particularly important with drugs that have _____.

Answer 33

Long half-lives

Question 34

The half-life assumption assumes _______.

Answer 34

First order kinetics

Question 35

First Order Kinetics means a ______ of the drug is metabolized per unit time.

Answer 35

Constant proportion

Question 36

_____ percent of steady state drug concentration is achieved in 3.3t1/2.

Answer 36

90

Question 37

How do you calculate clearance?

Answer 37

Clearance = (.693 x Vd) / (T1/2)

Question 38

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 ______.

Answer 38

Zero-order kinetics

Question 39

Repeated dosing of a drug won't allow for the drug to accumulate in the body unless the dosing interval is ________.

Answer 39

Less than 4T1/2

Question 40

________ of drugs into more polar molecules makes them less protein-bound at physiological pH and thus more readily filtered.

Answer 40

Biotransformation

Question 41

Accumulation of a drug is necessary in order for the drug to reach a _____ in the plasma.

Answer 41

Steady state

Question 42

Induced P450 enzymes metabolize drugs ______.

Answer 42

Faster

Question 43

What directions do half-lives work?

Answer 43

Reaching a steady state | Elimination

Question 44

What factors affect clearance?

Answer 44

Volume distribution Half life Kidney and liver function

Question 45

Drugs that are mostly ________ space have a smaller volume of distribution.

Answer 45

Confined to intravascular space

Question 46

What factors affect accumulation?

Answer 46

Method and frequency of dosing | Bioavailability

Question 47

____ is the drug concentration that will produce the desired therapeutic effect?

Answer 47

Target concentration

Question 48

Inhibited P450 enzymes metabolize drugs _____.

Answer 48

Slower

Question 49

The liver(and the GI tract to a much lesser degree) extensively by a transform struggle through its _____. complexes

Answer 49

Cytochrome P450

Question 50

Loading dose calculation

Answer 50

(Vd X target plasma concentration) / bioavailability

Question 51

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?

Answer 51

You can give a bigger loading dose

Question 52

______ P450 enzymes metabolize drugs slower.

Answer 52

Inhibited

Question 53

_________ can turn non-biologically active drugs into active drugs or convert drugs into even more active forms.

Answer 53

Biotransformation

Question 54

Formula for volume of distribution (Vd)

Answer 54

D/C^0 Amount of drug in body (dose) —————————————————————————— Concentration of drug in given compartment at time zero

Question 55

Cytochrome P450 Complexes are a large family of _____ with the enormous genetic variation.

Answer 55

Heme-containing enzymes

Question 56

______ are generally the same doses given at regular intervals.

Answer 56

Maintenance doses

Question 57

Maintenance dose formulas Dosing rate X dosing interval

Answer 57

(Clearance X target plasma concentration) / bioavailability

Question 58

_____ is the rate of drug metabolism and elimination is directly proportional to the concentration of free drug.

Answer 58

First order kinetics

Question 59

______ P450 enzymes metabolize drugs faster.

Answer 59

Induced

Question 60

________ administration of a drug results in oscillations in plasma concentrations that are influenced by both by both the rate of drug absorption and elimination.

Answer 60

Repeated fixed dose

Question 61

Phase ___ Biotransformation conjugates the drug with another chemical.

Answer 61

2

Question 62

A _____ dose given orally results in a single peak in plasma concentration followed by a continuous decline in drug level.

Answer 62

Single fixed dose

Question 63

The plasma concentrations during oral therapy fluctuate around the steady-state levels attained with ______.

Answer 63

Intravenous therapy

Question 64

When dosages are doubled, halved, are stopped during steady-state administration, the time required to achieve a new steady-state level is ____________________.

Answer 64

Independent of the route administration

Question 65

Where does the majority of biotransformation occur?

Answer 65

Liver

Question 66

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 ______.

Answer 66

Induction

Question 67

______ are a large family of heme-containing enzymes with the enormous genetic variation.

Answer 67

Cytochrome P450 Complexes

Question 68

Noncompetitive antagonist reduce agonist _____.

Answer 68

Efficacy (decrease Emax)

Question 69

________ can shorten the drugs biological half-life.

Answer 69

Biotransformation

Question 70

Phase ____ Biotransformation metabolizes the drug into a more polar form.

Answer 70

1

Question 71

What effect does biotransformation of a drug into a polar molecule?

Answer 71

Can greatly decrease activity and half-life

Question 72

Many lipophilic drugs are tightly bound to protein and thus unavailable for excretion by the _______.

Answer 72

Kidneys

Question 73

The drug receptor complex initiate alterations in biochemical and or molecular activity of a cell by a process called _____.

Answer 73

Signal transduction

Question 74

The phenomenon of desensitizing is called _______.

Answer 74

Tachyphylaxis

Question 75

During the recovery phase, unresponsive receptors are said to be ____.

Answer 75

Refactory

Question 76

____ of receptors can make the cells more sensitive to agonist and/or more resistant to the effect of the antagonist.

Answer 76

Up-regulation

Question 77

______ is a measure of the amount of drug necessary to produce an effect of a given magnitude.

Answer 77

Potency

Question 78

______ is the magnitude of response I drug causes when it interacts with the receptor.

Answer 78

Efficacy

Question 79

What does efficacy depend on?

Answer 79

The number of drug-receptor complexes formed | Intrinsic activity of the drug

Question 80

______ antagonist reduce agonist efficacy (____ Emax).

Answer 80

Noncompetitive Decrease

Question 81

_______ is the drugs ability to activate the receptor and cause a cellular response.

Answer 81

Intrinsic activity

Question 82

What does maximum efficacy assume?

Answer 82

That all receptors are occupied by the drug, and no increase in response is observed if a higher concentration of drug is obtained.

Question 83

The ______ of a drug determines its ability to fully or partially activate the receptors.

Answer 83

Intrinsic activity

Question 84

And agonist binds to a receptor it and produces a _____ based on the concentration of the agonist and the fraction activated receptors.

Answer 84

Biological response

Question 85

What is the value of the intrinsic activity for partial agonist?

Answer 85

Greater than zero but less than one

Question 86

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.

Answer 86

Allosteric

Question 87

_____ have an intrinsic activity less than zero, reverse the activity of receptors, and exert the opposite pharmacological effect of agonists.

Answer 87

Inverse agonist

Question 88

Competitive antagonist reduce agonist ______.

Answer 88

Potency (increase EC50)

Question 89

Which antagonist are considered non-competitive?

Answer 89

Irreversible | Allosteric

Question 90

_____ bind to a receptor with high affinity but possess zero intrinsic activity.

Answer 90

Antagonist

Question 91

An antagonist has no affect in the absence of an _____.

Answer 91

Agonist

Question 92

If both the antagonist in the agonist bind to the same site of the receptor in a reversible manner, they are said to be _____.

Answer 92

Competitive

Question 93

What does a competitive antagonist do?

Answer 93

Prevents the agonist from binding to its receptor which leaves the receptor in its in active state.

Question 94

_____ antagonist bind covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist.

Answer 94

Irreversible

Question 95

And Allosteric antagonist causes _____ shift of the Emax, with _____ shift of the EC50 values of agonist.

Answer 95

Downward No

Question 96

______ antagonist reduce agonist potency (____ EC50).

Answer 96

Competitive Increase

Question 97

An Irreversible antagonist causes _____ shift of the Emax, with _____ shift of the EC50 values (unless spare receptors are present).

Answer 97

Downward No

Question 98

This antagonist acts at a completely separate receptor, initiating effects that are functionally opposite those of the agonist

Answer 98

Functional antagonist

Question 99

What does the larger therapeutic index mean?

Answer 99

There is a wide margin between doses that are effective in doses that are toxic.

Question 100

Agents with low therapeutic index, which the dose is critically important, are those drugs for which ____ critically alters the therapeutic effects.

Answer 100

Bioavailability