Pharmacodynamics

Question 1

pharmacodynamics

Answer 1

the actions of a drug on a living organism

• mechanism of action
• receptor interaction

Question 2

a drug can modify a particular ____

Answer 2

cellular function or the rate of that function

Question 3

a drug can’t impart ____ to a cell or target tissue

Answer 3

a new function

Question 4

drug effect depends on ____

Answer 4

what the cell is capable of accomplishing

Question 5

drugs must ____ to have an effect

Answer 5

interact with a molecular target

Question 6

target is usually referred to as a ____

Answer 6

receptor

Question 7

selectivity of drug action is due to ____

Answer 7

receptors

Question 8

action of agonists and antagonists is mediated by ___

Answer 8

receptors

Question 9

when a drug binds to a receptor, one of the following usually occur:

Answer 9

• an ion channel is opened or closed
• biochemical messengers (second messengers) are activated (initiate a series of chemical reactions)
• a normal cellular function is inhibited
• a cellular function is “turned on” (ex: DNA transcription)

Question 10

Law of Mass Action:

-the combinations of drug (ligand) and receptor depends on ____

Answer 10

the concentrations of each

Question 11

Law of Mass Action:

-the amount of drug-receptor complex formed determines the ____

Answer 11

magnitude of the response

Question 12

Law of Mass Action:

-a minimum number of drug-receptor complexes must be formed for ____

Answer 12

a response to be initiated (threshold)

Question 13

Law of Mass Action:

-as drug concentration increases, the number of drug-receptor complexes ____ and drug effect ____

Answer 13

increases;

increases

Question 14

Law of Mass Action:

• a point will be reached at which all receptors are bound to a drug
• no further ____ can be formed
• response ____

Answer 14

complexes;

does not increase any further (saturation)

Question 15

drug-receptor complex formation is proportional to the concentrations of drug and receptor, but the relationship is not ____; pharmacologists usually use a ___ graph to ____

Answer 15

linear;
semilogarithmic;
linearize the relationship

Question 16

drug response is regulated by 2 properties:

Answer 16

1) affinity- the ability of the drug to bind to its receptor

2) efficacy- the ability of the drug to alter the activity of its receptor

Question 17

affinity

Answer 17

the strength with which a drug forms a complex with its receptor

Question 18

affinity is influenced by:

Answer 18

• size and shape of drug molecules
• types, number, and spatial arrangement of drug binding sites (stereochemistry)
• intermolecular forces between drug and binding sites

Question 19

drug concentration effect on affinity

Answer 19

NONE

Question 20

types of intermolecular forces

Answer 20

• Van der Walls forces
• hydrogen bonds
• covalent bonds

Question 21

Van der Walls forces

Answer 21

• weak bonds
• transient
• reversible

Question 22

hydrogen bonds

Answer 22

• intermediate bonds
• transient
• reversible

Question 23

covalent bonds

Answer 23

• strong bonds

- long-lasting and/or irreversible

Question 24

binding of drug to receptor usually involves ___ bonds

Answer 24

weaker

Question 25

there is a continuous ____ of the drug with the receptor as long as the drug is present

Answer 25

association and dissociation

Question 26

the ___ is a measure of a drug’s affinity

Answer 26

dissociation constant (Kd)

Question 27

Kd represents the ____

Answer 27

concentration of drug needed to ensure that 50% of the total receptor population is bound to the drug

Question 28

Kd does not always indicate ____

Answer 28

half-maximal response

Question 29

each drug-receptor combination will have a characteristic Kd value;
high affinity= _____ value for Kd
low affinity= _____ value for Kd

Answer 29

small;

large

Question 30

a cell will respond only to the spectrum of drugs that exhibit ____

Answer 30

affinity for the receptors expressed by the cell

Question 31

the greater the affinity for one receptor, the ____, which ____

Answer 31

more selective the drug’s actions;

lowers the potential for side effects

Question 32

few drugs are entirely ____ for one receptor;

many are ____ towards certain receptors based on affinity

Answer 32

specific;

selective

Question 33

as concentration increases, the drug will bind to receptors for which it has ____

Answer 33

lower affinity

Question 34

only those tissues ____ will respond to the drug

Answer 34

possessing receptors

Question 35

the more restricted the distribution of drug receptor, the _____

Answer 35

more selective will be the effects of drugs that interact with that receptor

Question 36

dose-response curve

Answer 36

gives representation of the relationship between amount of drug given and the anticipated effect

Question 37

2 types of dose-response curves

Answer 37

• graded

- quantal

Question 38

graded dose-response curve:

• measures ____
• similar shape to ____
• key points: ____

Answer 38

continual effect;
drug-receptor occupancy curve;
Emax, EC50

Question 39

Emax (graded dose-response curve)

Answer 39

dose beyond which no further response is achieved (maximal effect); measure of efficacy

Question 40

EC50

Answer 40

concentration (dose) that produces 50% of maximal response; measure of potency

Question 41

quantal dose-response curve:

• measures ____
• gives the relationship between ____
• key points: ____

Answer 41

responses that are all or none;
drug dose and the frequency with which a biologic effect occurs;
ED50, Emax

Question 42

ED50

Answer 42

dose of drug that produces a response in 50% of the population

Question 43

Emax (quantal dose-response curve)

Answer 43

dose at which all of the patients respond to the drug

Question 44

quantal dose-response curve:

-can be plotted for _____ effects

Answer 44

therapeutic, toxic, and lethal

Question 45

TD50

Answer 45

dose that produces toxic effects in 50% of the patient population

Question 46

LD50

Answer 46

dose at which 50% of patients die

Question 47

therapeutic index (TI)

Answer 47

a measure of the safety of a drug (larger is better!);

found by dividing the LD50 (or TD50) by the ED50

Question 48

agonist

Answer 48

binds to receptor and elicits a response

Question 49

antagonist

Answer 49

binds to receptor but does not elicit a response

Question 50

full agonists

Answer 50

produce maximum activation of the receptor and elicit a maximum response from the tissue

Question 51

partial agonists

Answer 51

produce weaker activation than full agonist or endogenous ligand; must be bound to more receptors to produce same effect as full agonist

Question 52

inverse agonists

Answer 52

inhibit receptors that exhibit activity in the absence of agonist binding; binding of inverse agonist reduces the baseline activity of the receptor; technically an agonist because it causes a response

Question 53

antagonists

Answer 53

have zero intrinsic activity; do not cause a reaction, simply prevent the receptor from being occupied by another molecule

Question 54

competitive reversible antagonists

Answer 54

• antagonist competes directly with the agonist molecule
• increasing the concentration of the agonist will eventually overcome the antagonism
• Emax is the same but curve shifted to the right

Question 55

competitive irreversible antagonists

Answer 55

• compete directly with agonist for receptor binding site
• bond is so strong that it is irreversible
• permanently reduces number of receptors available to an agonist
• reduces the maximal agonist effect

Question 56

noncompetitive antagonist

Answer 56

• do not compete with agonist for same binding site
• impair the ability of the agonist to bind to or activate the receptor
• both antagonist and agonist can be bound at the same time
• increasing concentration of agonist will not reverse the inhibitory action
• similar curve to irreversible agonist
• difference may be in duration of action

Question 57

4 families of receptors

Answer 57

• ligand-gated ion channels
• G protein-coupled receptors
• enzyme-linked receptors
• intracellular receptors

Question 58

ligand-gated ion channels

Answer 58

• regulates ion flow across membranes
• flow of ions through these channels is dependent on binding of a ligand (neurotransmitter, drug) to the receptor on the channel
• ion channel possesses a receptor for an endogenous ligand (agonist usually binds to same receptor)
• activation by endogenous ligand or agonist opens the channel (antagonists prevent activation of the channel or cause it to remain closed)

Question 59

ligand-gated ion channel examples

Answer 59

• cholinergic receptors: found in nervous system, binding of agonist opens sodium channels and causes initiation of action potential
• GABA receptors: found in CNS, binding of agonist opens chloride channels, causing hyperpolarization (reduce probability of action potential)

Question 60

voltage-gated ion channels

Answer 60

• change conformation in response to changes in membrane voltage
• binding of drugs to these channels causes a change in the response of the channel
• open, closed, or inactive state may be lengthened or shortened
• ex: local anesthetics

Question 61

G-protein coupled receptors

Answer 61

• single peptide that has seven membrane-spanning regions
• linked to a G-protein
• binding of ligand to the extracellular region of the receptor activates the G-protein

Question 62

G-protein has ___ subunits: ____

Answer 62

3;

alpha, beta, and gamma

Question 63

activation of G-protein coupled receptors

Answer 63

• GTP replaces GDP on the alpha subunit
• alpha-GTP and beta-gamma subunits dissociate and interact with other cellular effectors (enzymes or ion channels)
• change the concentrations of intracellular second messengers that are responsible for further actions within the cell
• slightly slower response but lasts longer (several seconds to minutes, “slow on” and “slow off”)

Question 64

second messengers are important in ____

Answer 64

conducting and amplifying signals from G-protein coupled receptors

Question 65

enzyme-linked receptors

Answer 65

• have cytosolic enzyme activity as part of their structure and function
• binding of the ligand to the receptor activates or inhibits the activity of the enzyme
• receptor undergoes conformational change upon binding
• longer duration (minutes to hours)

Question 66

enzyme-linked receptors:

• ____ can modify the three-dimensional structure of the target protein
• acts as a ____
• ____ that multiplies initial signal
• examples: ___

Answer 66

addition of a phosphate group;
molecular switch;
cascade activation;
insulin receptor, VEGF

Question 67

intracellular receptors

Answer 67

• receptors are located intracellularly
• ligand must be lipid soluble
• example: steroid hormones
• binding of ligand with its receptor causes dissociation of a small repressor peptide and activates the receptor
• complex migrates to the nucleus where it binds to specific DNA sequences
• results in regulation of gene expression
• much longer time course (due to change in gene expression, 30 mins or more to observe response, response lasts hours to days)

Question 68

spare receptors

Answer 68

• in some cases, a maximal response can be achieved when only a fraction of receptors are occupied (EC50 is much lower than the Kd)
• due to amplification of signal duration and intensity
• common with G-protein linked receptors

Question 69

spare receptors:

amplification occurs by two phenomena

Answer 69

• a single ligand receptor complex can interact with many G-proteins
• an activated G-protein can persist for a longer duration than the original ligand-receptor complex

-because the amplification only involves a fraction of the total receptors for a specific ligand, the system is said to have spare receptors

Question 70

receptor desensitization

Answer 70

• repeated or continuous administration of a ligand may lead to changes in the responsiveness of the receptor
• evolved to prevent cell damage

Question 71

two mechanisms of receptor desensitization

Answer 71

• tachyphylaxis

- endocytosis

Question 72

receptor desensitization: tachyphylaxis

Answer 72

receptor is still present but is unresponsive to the ligand

Question 73

receptor desensitization: endocytosis

Answer 73

• binding causes conformational change in receptor

- receptor undergoes endocytosis and is sequestered from further activation

Question 74

tolerance

Answer 74

• decreased response to a drug
• dose must be increased to achieve the same effect
• can be metabolic, cellular (downregulation), or behavioral

Question 75

dependence

Answer 75

• patient needs a drug to function “normally”

- usually physical but CAN have a psychological component

Question 76

withdrawal

Answer 76

• drug is no longer given to a dependent patient

- symptoms are often the opposite of the effect of the drug

Question 77

there may be considerable variation in the way that patients respond to medication for multiple reasons:

Answer 77

• alteration in the concentration of drug that reaches the receptor
• variation in concentration of endogenous ligand
• alteration in number of receptors
• changes in components of response

Question 78

most drugs interact with receptors that will determine ____

Answer 78

selective therapeutic and toxic effects of the drug

Question 79

receptors largely determine the _____

Answer 79

quantitative relations between dose of a drug and pharmacologic effect