Pharmacodynamics

Question 1

which one of Paul Ehrlich’s theories used the analogy of a lock & key?

Answer 1

the side chain theory & concept of the receptor

Question 2

what was the lock and key analogy implying relating to a ligand & a receptor?

Answer 2

1. key goes in and out (reversible binding)
2. key must fit lock (selective binding)
3. only certain keys turn the lock (selectivity of action)
4. thermodynamic (energetically favorable to obtain binding/action)

Question 3

most receptors have endogenous naturally occurring molecule that

Answer 3

bind to them

Question 4

exogenous drugs have to be designed to

Answer 4

bind and mimic the endogenous substance at the same receptor

Question 5

give an example of an endogenous molecule and exogenous drug acting through the same receptor class

Answer 5

endorphins & morphine bind to opiate receptors in the brain

Question 6

what chemical bond determines if a drug-receptor complex is irreversible

Answer 6

covalent

Question 7

what chemical bond determines if a drug-receptor complex is reversible by altering pH

Answer 7

ionic

Question 8

what chemical bond determines if a drug-receptor complex is readily reversible

Answer 8

• hydrogen
• hydrophobic
• van der Waals

Question 9

define stereoisomers

Answer 9

chemical structures that are chemically identical but have different orientations around the single bond

Question 10

what effect can stereoisomers have on drug affinity?

Answer 10

it can alter affinity of a drug to its receptor therefore affecting its potency

Question 11

define hydrophobic

Answer 11

• water hating
• fat loving
• nonpolar

Question 12

define hydrophilic

Answer 12

• water loving
• fat hating
• polar

Question 13

define lipophilicity

Answer 13

allows drugs to move among body compartments and bind to receptors

Question 14

what are the 4 requirements for good drug binding

Answer 14

1. receptor specificity
2. type of bond formed
3. stereoselectivity
4. solubility characteristic

Question 15

define agonists

Answer 15

bind to produce and elicit
- max. activation of receptor
- max response from the tissue

Question 16

define antagonists

Answer 16

bind but produce
- NO activation of receptor
- block response from tissue

Question 17

define partial agonists

Answer 17

produce weaker activation of receptor than full agonists or endogenous ligands

Question 18

define inverse agonists

Answer 18

inhibit rather than activate the receptor

Question 19

define allosteric modulators

Answer 19

bind to receptors at alternate binding site

Question 20

define potency

Answer 20

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

Question 21

what is EC50

Answer 21

the [] of a drug needed to produce 50% of the maximum effect

Question 22

what is ED50

Answer 22

dose that produces 50% of maximal response

Question 23

define efficacy

Answer 23

ability of a bound drug to change the receptor in a way that produces an effect

Question 24

what is Emax

Answer 24

the maximal efficacy of a drug

Question 25

define therapeutic index (TI)

Answer 25

ratio of LD50/TD50 and ED50

Question 26

which if the 2, efficacy or potency, is a more useful value?

Answer 26

efficacy

Question 27

why is the efficacy a more clinically useful value than potency?

Answer 27

b/c a drug with greater efficacy is more therapeutically beneficial that one that is more potent

Question 28

what is LD50

Answer 28

the dose at which 50% of patients die

Question 29

what is TD50%

Answer 29

the dose at which toxicity occurs in 50% of patients

Question 30

drugs with which type of therapeutic window are more desirable?

Answer 30

those with a greater/wider therapeutic window

Question 31

drug binding specificity involves

Answer 31

molecular recognition between ligand and receptor

Question 32

drug binding specificity requires

Answer 32

spatially & energetically complementary domains

Question 33

explain the concept of binding affinity/ binding energy

Answer 33

- recognition between receptor and ligand - spatially/ energetically complementary domains

Question 34

equilibrium binding constant KD represents...

Answer 34

rate of dissociation/ rate of association

Question 35

what information does KD provide about a drug?

Answer 35

drugs w/ a high affinity display a small KD value

Question 36

KD= the drug concentration that gives

Answer 36

50% bound receptors

Question 37

KD is inversely related to

Answer 37

drug binding affinity

Question 38

receptor classifications are named after an

Answer 38

endogenous ligand w/ various subtypes of receptors named for exogenous agents

Question 39

what is an example of a ligand gated ion channel?

Answer 39

in skeletal muscles for movement of NA+ and Ca2+ - nicotinic cholinergic receptors - endogenous ligand acetylcholine

Question 40

explain GPCRs | G-protein coupled receptors

Answer 40

7 transmembrane domains spanning region of the receptor w/ few allosteric modulator binding sites

Question 41

GPCRs activate

Answer 41

2nd messenger systems within the intracellular space

Question 42

which receptors represent the largest protein class of receptors in the human genome?

Answer 42

GPCRs

Question 43

gives examples of GCPR receptors

Answer 43

- muscarinic cholinergic receptors - adrenergic (a & b ) - dopaminergic - serotonergic

Question 44

give examples of endogenous ligands that bind to GCPRs

Answer 44

- acetylcholine - epinephrine - norepinephrine - dopamine - serotonin - GABA - glucagon

Question 45

the GCPR are found in the

Answer 45

- heart - respiratory system - digestive system - blood vessels

Question 46

what are RTKS | receptor tyrosine kinases

Answer 46

single transmembrane spanning regions

Question 47

describe the mechanism of RTKs

Answer 47

binding of ligand causes dimerization of the kinases following phosphorylation by ATP

Question 48

give examples of ligands that bind to RTKs

Answer 48

- insulin - GF GH

Question 49

ligand binding occurs on what side of the cell?

Answer 49

on the extracellular side

Question 50

nuclear receptors are ..

Answer 50

receptor residues that are on the inside of the cell or within the nucleus

Question 51

in nuclear receptors the ligand-receptor complex binds to

Answer 51

DNA segment for transcription

Question 52

what is a unique characteristic of nuclear receptors?

Answer 52

they have longer lasting effects than other ligand-binding receptors

Question 53

what are some examples of endogenous receptors that bind to nuclear receptors?

Answer 53

- corticosteroids - mineralocorticoids - sex steroids (estrogen & testosterone) - vit. A and D

Question 54

what are the 4 known changes that can occur in receptor quantities?

Answer 54

- receptor quantities are not constant - internalization & degradation - change in receptor synthesis rate - can be unregulated or downregulated

Question 55

describe upregulation

Answer 55

receptor number increase due to a decrease of activity in the receptor

Question 56

describe downregulation

Answer 56

receptor number decreases due to an increase making the cell less sensitive to the ligand

Question 57

describe desensitization/tolerance

Answer 57

continued stimulation of a receptor system will depress the effect produced by an administered drug - a higher dose is requires to each the same effect