Lecture 2: Pharmacokinetics

Question 1

in general, what is a drug?

Answer 1

any substance that causes a change in biological effect

Question 2

epinephrine is an ___ in the heart

Answer 2

agonist

Question 3

administration of epinephrine causes and increase in __ and __

Answer 3

heart rate and contractile force

Question 4

t/f an increase in concentration of epinephrine caused an increase in response

Answer 4

true

Question 5

what is represented by Emax?

Answer 5

the max physiologic effect achieved by a drug

Question 6

Emax is a measure of __

Answer 6

efficacy

Question 7

what is represented by Ed50?

Answer 7

the dose needed to reach 50% maximal response

Question 8

ED50 is a measure of __

Answer 8

potency

Question 9

two drugs can be equally effective, but Ifone drug requires a smaller dose to reach the same response, it is said to be more __

Answer 9

potent

Question 10

a lower ED50 means __

Answer 10

the drug is more potent

Question 11

comparisons of drugs should be made between drugs that produce the same ___ and ideally at the same __

Answer 11

response; receptor

Question 12

graded response curves are useful for comparing parameters in ____

Answer 12

controlled experimental system

Question 13

when comparing two drugs in a cell based assay, what type of dose curve would you use?

Answer 13

graded response curve

Question 14

quantal dose is important to determining ___ and ___

Answer 14

range of therapeutic doses and doses where toxicity arises

Question 15

therapeutic window

Answer 15

range of doses with therapeutic effect and minimal toxicity

Question 16

the therapeutic index is measured as the ration of ___ over __

Answer 16

Td50/Ed50

Question 17

as the therapeutic index (TI) increases, what will happen to the Effective and Toxic curves?

Answer 17

they will be further apart

Question 18

as a therapeutic index increases, what happened to the safety of the drug?

Answer 18

increases

Question 19

t/f the E and T curves can sometimes overlap

Answer 19

true

Question 20

what does it mean when the E and T curves overlap?

Answer 20

that in order for the drug to be effective, some patients required a dose that was found to be toxic in some other patients

Question 21

if a drug has a small therapeutic window, a small increase in dose could be expected to result in

Answer 21

more risk of adverse reactions

Question 22

patients should be closely monitored if the drug has a __ therapeutic window

Answer 22

small

Question 23

give an example of a drug with a small therapeutic window

Answer 23

warfarin

Question 24

drugs with a __ therapeutic index and window can be given in large doses to reach effective dose with little risk of adverse effects

Answer 24

large

Question 25

give an example of a drug with a large therapeutic window

Answer 25

penicillin

Question 26

what is a receptor?

Answer 26

protein within a cell that is capable of modulating cellular effects based on the binding of drug or endogenous molecules

Question 27

activation of a receptor results in __

Answer 27

cellular response

Question 28

agonist binds preferentially to ___ receptors and stabilizes this conformation, resulting in a shift towards more __ and therefore more __

Answer 28

active; active conformation and physiologic effect

Question 29

t/f binding of drug to receptor determines the level of effect

Answer 29

true

Question 30

what is represented by Bmax/

Answer 30

max receptor binding

Question 31

Kd is the __ constant

Answer 31

dissociation

Question 32

what is represented by the Kd?

Answer 32

drug concentration required to produce 50% receptor occupancy

Question 33

the Kd value is a measure of the drug __ for the __

Answer 33

Affinity; receptor

Question 34

if you increase the __ of a drug, you better the chances of receptor binding, even if the affinity is low

Answer 34

dose

Question 35

is there a 1:1 ratio between receptor binding and graded response?

Answer 35

not usually

Question 36

explain the concept of spare receptors

Answer 36

not all receptors may need to be bound to agonist in order for the full response to be achieved

Question 37

drug's affinity can be used as a measure of __

Answer 37

selectivity

Question 38

t/f it is very rare for a drug to be 100% selective for a specific receptor @ any given dose

Answer 38

treu

Question 39

in most cases, a drug is more selective because it has a higher ___ for one receptor than another

Answer 39

affinity

Question 40

how can knowledge about affinity be used to better drug therapy? Refer to example of prazosin and tamsulosin

Answer 40

prazosin and tamsulosin are drugs used to treat urine retention. praz has a higher affinity for A receptors in the blood vessels, but can cause orthostatic hypertension. Tamsulosin is designed to have higher affinity for B receptors in urinary tract (no dizziness)

Question 41

t/f Kd can provide indication of response, efficacy, and/or potency

Answer 41

false

Question 42

what causes off-target drug effect?

Answer 42

binding of drug to an unintended receptor

Question 43

what is one of the most common causes of adverse dug effects?

Answer 43

unintended and off-target drug effects

Question 44

what are three questions to ask when predicting off-target drug effects?

Answer 44

1. is the target receptor expressed in other tissues? 2. does the drug easily distribute to other tissues? 3. does the drug have affinity for other tissue receptors?

Question 45

t/F off-target drug effects are always adverse

Answer 45

false

Question 46

explain the example of histamine as an on-target but in wrong tissue

Answer 46

blocking histamine receptors in the periphery manages the symptoms of allergies, but blocking the receptors in the CNS results in sedation

Question 47

what are idiosyncratic effects?

Answer 47

effects that have origin/cause that is unrelated to known interactions of drug / receptors

Question 48

allergic effects can sometimes be predicted, but are unrelated to the ___ of the drugs and are rather caused by __

Answer 48

pharmacological properties; immune system

Question 49

propanolol is an example of a __ blocker

Answer 49

beta

Question 50

if propranolol (a beta blocker) is administered before a dose of epinephrine, what is the result on heart rate?

Answer 50

no change

Question 51

antagonists are classes by __

Answer 51

method used to reach blocking / inhibitory effect

Question 52

non-receptor class antagonists do not __

Answer 52

bind to receptor

Question 53

what are chemical non-receptor antagonists?

Answer 53

drugs that bind to another to prevent action of agonist

Question 54

provide an example of chemical non-receptor antagonist

Answer 54

protamine sulfate to heprin

Question 55

what are physiological non-receptor antagonists?

Answer 55

counteract agonist effect by modulating a different target

Question 56

give an example of physiological non-receptor antagosnt

Answer 56

diazepam against epinephrine

Question 57

explain the concept of receptor antagonists

Answer 57

interact with the receptor in the same way the agonist would

Question 58

what are the 2 types of receptor class antagonists?

Answer 58

1. orthostatic ("active") | 2. allosteric

Question 59

what is the role of orthostatic receptor antagonists?

Answer 59

binds to same site as agonist and can be reversible or irreversible

Question 60

reversible orthstatic receptor antagonists are called

Answer 60

competitive antagonists

Question 61

irreversible orthostatic antagonists are called

Answer 61

non-competitive antagonists

Question 62

allosteric receptor antagonists bind to ___

Answer 62

non-active site of receptor

Question 63

t/f allosteric receptor antagonist binding can be either reversible or irreversible

Answer 63

true

Question 64

both reversible and irreversible allosteric receptor antagonists are called

Answer 64

allosteric antagonist

Question 65

most antagonist binding is __

Answer 65

reversible

Question 66

ASA binding is ___ and inhibits ___ (the key enzyme in platelet aggregation

Answer 66

irreversible; COX-1

Question 67

why is ASA binding irreversible?

Answer 67

platelets cannot make new receptors because they do not have a nucleus and will just die away anyway

Question 68

competitive antagonists can be __ by the agonist

Answer 68

bumped out of place

Question 69

you can totally negate the antagosnt by __. However, the agonist will still experience a significant loss in __

Answer 69

increasing the concentration of agonist; potency

Question 70

non-competitive antagonists interact __ with the agonist site or bind the ___ site

Answer 70

strongly; allosteric

Question 71

why does increasing the concentration of agonist not affect response when in the presence of a non-competitive antagonist?

Answer 71

the antagonist binds to a site different than active site the agonist binds to

Question 72

when an allosteric antagonist binds, it makes a ___ to the receptor, which prevents __

Answer 72

conformational change; binding of agonist to active site

Question 73

non-ciometive antagonists cause a decrease in __- and possibly ___

Answer 73

efficacy and potency

Question 74

if an antagonist binds irreversibly, what must happen to restore full response?

Answer 74

new receptor must be made

Question 75

if an antagonist binds reversibly, what must happen to restore full response?

Answer 75

wait it out, time course is amount of time taken for antagonist to release from the allosteric site

Question 76

allosteric antagonists may also be called __

Answer 76

negative allosteric modulators

Question 77

what is the effect of allosteric antagonists?

Answer 77

can decrease or increase the ability of the agonist to bind

Question 78

positive allosteric modulators bind to what site on receptor?

Answer 78

non-active site

Question 79

positive allosteric modulators may increase both __ and __

Answer 79

efficacy and potency

Question 80

benzodiazepines are PAMs of the __ receptors

Answer 80

GABA

Question 81

t/f antagonists are capable of producing a response on their own

Answer 81

false

Question 82

t/f antagosnts have no defined Emax for efficacy

Answer 82

true

Question 83

role of inverse agonists

Answer 83

cause reduction of effect below baseline levels by stabilizing the inactive receptor conformation

Question 84

inverse agonists cause the equilibrium to shift towards __

Answer 84

Ri

Question 85

it is very difficult to measure the effect of inverse agonists if the constitutive activity is very __ and in this case, it may be classed as a __ agonist

Answer 85

low ; neutral

Question 86

t/f it is not clinically clear if there is a difference between antagonists and inverse agonists

Answer 86

true