Block 1 Lecture 3 -- Pharmacodynamics I

Question 1

ligand:

Answer 1

molecules that binds to some other type of biological entity

Question 2

receptor:

Answer 2

protein that interacts with a ligand resulting in a change in physiological activity

Question 3

drug mechanism of action:

Answer 3

the physicochemical relationship between a drug and its specific target, and the cascade of biochemical signaling that ensues

Question 4

placebo response:

Answer 4

inert substance given to a patient that leads to clinical improvement

Question 5

nocebo response:

Answer 5

inert substance that causes a worsening of Sxs or development of ADRs

Question 6

adverse drug response:

Answer 6

undesirable drug response

Question 7

idiosyncratic drug response:

Answer 7

a quantitatively abnormal drug response

Question 8

drug allergy:

Answer 8

an adverse immunologic reaction to a drug

Question 9

agonist:

Answer 9

ligand that binds receptor and activates it

Question 10

partial agonist:

Answer 10

a drug with less than maximal effect in comparison to a full agonist

Question 11

indirect-acting agonist:

Answer 11

drug that increases synaptic concentration of endogenous neurotransmitter

Question 12

allosterically-acting ligand:

Answer 12

ligand that interacts at a non-orthosteric site where it can potentiate functional response to an endogenous ligand

Question 13

chemical antagonist:

Answer 13

a compound that chemically combines with a xenobiotic to prevent delivery of that substance to its normal site of action

Question 14

physiologic antagonist:

Answer 14

a drug that blocks a physiological response related to a particular condition without actually affecting the state of that condition

Question 15

receptor (pharmacological) antagonist:

Answer 15

drug that prevents formation of agonist-receptor complexes

Question 16

competitive antagonist:

Answer 16

drug that competes with NTs for access to orthosteric binding sites

Question 17

non-competitive antagonist:

Answer 17

drug that binds receptor at a non-orthosteric site

Question 18

irreversible antagonist:

Answer 18

drug that binds covalently to a receptor

Question 19

indirect antagonist:

Answer 19

drug that decreases synaptic concentration of NT

Question 20

inverse agonist:

Answer 20

drug that produces physiological effects opposite to those of an agonist

Question 21

potency:

Answer 21

the relationship between a drug concentration and its biological response in comparison to another drug

Question 22

Quantal Dose Response Curve:

Answer 22

graph used to plot “all or nothing” drug responses; commonly used to assess responses across large patient population

Question 23

efficacy

Answer 23

the ability of a drug to produce a desired effect

Question 24

constitutive activity:

Answer 24

activity present in the GPCRs of some systems to produce physiologically active effects even in the absence of agonist

Question 25

on-target ADR:

Answer 25

drug hits intended target excessively or in the wrong location

Question 26

off-target ADR:

Answer 26

drug interacts with unintended targets

Question 27

direct-acting agonist:

Answer 27

drug with enough structural similarity to an endogenous ligand to bind to and directly activate NT receptors

Question 28

Partial agonists are aka…

Answer 28

functional antagonists

Question 29

What are the mechanisms by which indirect-acting agonists might work?

Answer 29

1) block NT degradation
2) block re-uptake transporters
3) increase pre-synaptic release

Question 30

What are the types of antagonism?

Answer 30

1) PK
2) chemical
3) physiologic
4) receptor (pharmacological)

Question 31

Describe the structure of the nAChR

Answer 31

5 subunits like GABAa but excitatory

Question 32

Describe structure of the GABAa receptor

Answer 32

5 subunits surrounding inhibitory Cl- channel

• 2 orthosteric GABA sites
• allosteric: EtOH, BZDs, neurosteroids, barbiturates

Question 33

Axes of a DRC:

Answer 33

% response vs. [drug]

Question 34

ED50:

Answer 34

[agonist] that produces a 50% maximal response

Question 35

IC50

Answer 35

ED50 for antagonist–

[antagonist] to decrease agonist response by 50%

Question 36

examples of irreversible antagonists:

Answer 36

organophosphates

snake toxins

Question 37

examples of chemical antagonism:

Answer 37

1) mercury + dimercaprol
2) anti-venoms
3) immunotherapy for addiction

Question 38

examples of physiologic antagonism:

Answer 38

1) epinephrine + histamine

2) beta-blockers in hyperthyroidism

Question 39

example of receptor antagonism:

Answer 39

propranolol + NE

Question 40

What are the mechanisms by which indirect antagonists might work?

Answer 40

1) block NT synthesis

2) decrease pre-synaptic NT release

Question 41

What factors could cause an idiosyncratic drug response?

Answer 41

1) reactive metabolites
2) non-allergic changes in pt immune system
3) specific gene mutations in receptor