Exam 1 - Drug-receptor Interactions and Pharmacodynamics

Question 1

pharmacokinetics = __________

Answer 1

ADME (absorption, distribution, metabolism, excretion)

Question 2

A small number of clinically useful drugs do not require a ____________ to evoke their biological response such as _______ drugs, _______ for heavy metal poisoning and most ________.

Answer 2

A small number of clinically useful drugs do not require a target receptor to evoke their biological response such as osmotic drugs, antidotes for heavy metal poisoning and most laxatives.

Question 3

Most drugs work in a __________ way, i.e. their therapeutic as well as toxic effects stem from their ___________, collectively known as __________.

Answer 3

Most drugs work in a structurally specific way, i.e. their therapeutic as well as toxic effects stem from their interactions with specific cellular target molecules, collectively known as receptors.

Question 4

Pharmacologically a receptor is a ________________ that is present mostly on the __________, but also within the __________ or __________ that binds to a specific molecule such as a neurotransmitter, hormone, metabolite, or a drug molecule and thereby initiating cellular response.

Answer 4

Pharmacologically a receptor is a cellular macromolecule that is present mostly on the cell membrane, but also within the cytoplasm or cell nucleus that binds to a specific molecule such as a neurotransmitter, hormone, metabolite, or a drug molecule and thereby initiating cellular response.

Question 5

Drug-induced changes in the biochemical and biophysical properties of the receptor result in ____________________ that constitute the ___________ of the drugs.

Answer 5

Drug-induced changes in the biochemical and biophysical properties of the receptor result in physiological changes that constitute the biological actions of the drugs.

Question 6

Receptors largely determine the quantitative relations between_____________ of drug and ____________.

Answer 6

Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects.

Question 7

The receptor’s __________ for binding a drug determines the ______________ of drug required to form a significant number of drug-receptor complexes, and ___________________________ may limit the maximal effect a drug may produce.

Answer 7

The receptor’s affinity for binding a drug determines the concentration of drug required to form a significant number of drug-receptor complexes, and the total number of receptors may limit the maximal effect a drug may produce.

Question 8

Multiple chemical interactions occur, some of which are fairly weak (such as___________) and some of which are extremely strong (such as ___________).

Answer 8

Multiple chemical interactions occur, some of which are fairly weak (such as van der Waals’ forces) and some of which are extremely strong (such as covalent bonding).

Question 9

______________, which is usually experimentally reported by the KD value, is a measure of the ___________

Answer 9

Affinity, which is usually experimentally reported by the KD value, is a measure of the favorability of a drug–receptor interaction.

Question 10

Even a minor variation in the functionalities of the drug molecules can significantly alter the binding interactions and thus the ___________ that eventually contributes to the overall _______, ________, and ________ of drug action.

Answer 10

Even a minor variation in the functionalities of the drug molecules can significantly alter the binding interactions and thus the affinity that eventually contributes to the overall potency, efficacy, and duration of drug action.

Question 11

Most drug receptors are __________ in nature and fall into multiple different categories

Answer 11

Most drug receptors are proteins in nature and fall into multiple different categories

Question 12

Receptor classes : inotropic receptors

Answer 12

inotropic receptors or ion channels are ligand gated channels and voltage gated channels

Question 13

receptor classes : Metabotropic receptors

Answer 13

receptor classes : Metabotropic receptors are G-protein coupled receptors that bind to endogenously produced hormones (neurotransmitters?)

Question 14

receptor classes: kinase linked and related receptors

Answer 14

kinase linked and related receptors are receptors for various growth factors and thus for some anticancer drugs.

Question 15

receptor classes: nuclear receptors are receptors for __________ hormone, some _________ and ________.

Answer 15

nuclear receptors are receptors for thyroid hormone, some fat soluble vitamins and steroids.

Question 16

What are the receptors that are proteins that don’t have the word “receptor” in their name.

there are 3

Answer 16

enzymes, cytoskeletal or structural proteins, transporters or carrier proteins.

Question 17

What are the non protein receptors? there are 3

Answer 17

nucleic acids (RNA, DNA), membranes, and fluid compartments

Question 18

Many of the receptor subfamilies, notably the ________________ superfamily and _______________ receptors, can be coupled to respective _________ or _________ components that orchestrate diverse cellular effects which may occur over a wider time scale.

Answer 18

Many of the above receptor subfamilies, notably the G-protein coupled receptor (GPCR) superfamily and growth factor receptors, can be coupled to respective executioner or effector components that orchestrate diverse cellular effects which may occur over a wider time scale.

Question 19

Describe occupancy theory

Answer 19

the more receptors that are occupied by a drug the higher the response. This theory also suggests that if all the receptors are occupied by the drug then the maximum possible response is initiated.

Question 20

The term Kd is a ____________ and it quantifies the “__________” for a particular drug for its receptor. If the Kd is _____, the binding affinity is ________ and_________

Answer 20

The term Kd is a concentration and it quantifies the “affinity” for a particular drug for its receptor. If the Kd is low, the binding affinity is high, and vice versa

Question 21

Since concentration of receptor is __________ within a tissue, a large increase in drug concentration will lead to ____________ binding with various nonspecific sites other than the t_____________. this may create ________________.

Answer 21

Since concentration of receptor is finite within a tissue a large increase in drug concentration will lead to secondary less affinity binding with various nonspecific sires other than the target receptor protein. this may create unwanted side effects.

Question 22

What are the limitations to occupancy theory (2)

Answer 22

1. even at extremely high doses partial agonists are unable to achieve maximum response

2.some agonists are able to achieve maximal effectiveness at extremely low receptor occupancies.

Question 23

In most cases, tissues rather have ‘_______________________’ and drugs need to occupy only a minor proportion (≤10%) of the total receptor population to _____________________.

Answer 23

In most cases, tissues rather have ‘spare receptors or receptor reserve’ and drugs need to occupy only a minor proportion (≤10%) of the total receptor population to evoke a maximum response.

Question 24

Are Kd and EC50 always equal?

Answer 24

no, because of the spare receptors.
if there are spare receptors EC50 does not = Kd

Question 25

The overall transduction process that links drug occupancy of receptors and pharmacologic response is called___________.

Answer 25

The overall transduction process that links drug occupancy of receptors and pharmacologic response is calledcoupling.

Question 26

Coupling is also determined by “____________” biochemical events that transduce receptor occupancy into ______________

Answer 26

Coupling is also determined by “downstream” biochemical events that transduce receptor occupancy into cellular response

Question 27

Receptors are said to be “spare” for a given pharmacologic response if it is possible to elicit a ________________________ at a concentration of agonist that does not result in occupancy of all of the available receptors .

Answer 27

Receptors are said to be “spare” for a given pharmacologic response if it is possible to elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of all of the available receptors .

Question 28

Upon binding at specific binding site(s) on their receptors, drugs can either mimic the action of endogenously produced ligands as _________ or can oppose the biological effects of the endogenous ligands as __________.

Answer 28

Upon binding at specific binding site(s) on their receptors, drugs can either mimic the action of endogenously produced ligands as agonists or can oppose the biological effects of the endogenous ligands as antagonists.

Question 29

In the presence of a fixed concentration of agonist, increasing concentrations of a___________________ progressively inhibit the agonist response; high __________ concentrations prevent the response almost completely.

Answer 29

In the presence of a fixed concentration of agonist, increasing concentrations of acompetitive antagonist progressively inhibit the agonist response; high antagonist concentrations prevent the response almost completely.

Question 30

conversely, sufficiently high concentrations of agonist can __________________ of the antagonist; that is, the Emaxfor the agonist remains the same for any fixed concentration of antagonist.

Answer 30

onversely, sufficiently high concentrations of agonist can surmount the effect of a given concentration of the antagonist; that is, the Emaxfor the agonist remains the same for any fixed concentration of antagonist.

Question 31

The ability of a ligand to initiate receptor activation is termed as _____________. Agonists therefore have both __________ and _______ for cognate receptors.

Answer 31

The ability of a ligand to initiate receptor activation is termed as efficacy. Agonists therefore have both affinity and efficacy for cognate receptors.

Question 32

Compare full, partial and inverse agonists
full - mimic _________ ________
partial - activate receptors but are unable to ________________
inverse - causes _______________.

Answer 32

full - mimic physiological agonists
partial - activate receptors but are unable to elicit the mac response of the receptor system
inverse - causes active targets to become inactive.

Question 33

Antagonists thus have _______ but lack ______ for their target receptors.

Answer 33

Antagonists thus have affinity but lack efficacy for their target receptors.

Question 34

competitive antagonists are also known as (usually) ________ and are bound through a ________ bond

Answer 34

reversable
non-covalent

Question 35

non-competitive or __________ inhibition are the _______- bonds.

Answer 35

irreversible inhibition
covalent bonds

Question 36

Competitive inhibitor occupies the active site and prevents _____________ (i.e. ________ produced) __________.

Answer 36

Competitive inhibitor occupies the active site and prevents binding of the physiological (i.e. endogenously produced) ligands.

Question 37

Non-competitive or irreversible inhibitor covalently binds at the active site of the enzyme and _____________.

Answer 37

Non-competitive or irreversible inhibitor covalently binds at the active site of the enzyme and irreversibly inhibits it.

Question 38

Allosteric inhibitor binds at sites other than the active site, causing a ___________________ in the enzyme that prevents it from __________________-.

Answer 38

Allosteric inhibitor binds at sites other than the active site, causing a conformational change in the enzyme that prevents it from binding to its physiological substrate.

Question 39

Physiological antagonists: two drugs acting on different ___________ have opposing ________________

Answer 39

Physiological antagonists: two drugs acting on different cognate receptors have opposing pharmacological actions;

Question 40

Pharmacokinetic antagonists: reduce ____________, and thus the concentration of an agonist at its site of action through ____________________ in the liver

Answer 40

Pharmacokinetic antagonists: reduce bioavailability, and thus the concentration of an agonist at its site of action through induction of drug metabolizing enzymes in the liver

Question 41

partial agonists competitively inhibit the responses produced by full agonists. this mixed “______________” property of partial agonists can have both beneficial and deleterious effects in the clinic.

Answer 41

partial agonists competitively inhibit the responses produced by full agonists. this mixed “agonist-antagonist” property of partial agonists can have both beneficial and deleterious effects in the clinic.

Question 42

Go over the 5 types of mechanisms of transmembrane signaling

Answer 42

k

Question 43

Potency refers to the __________________ or __________________ of a drug required to produce 50% of that drug’s __________.

Answer 43

Potency refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect.

Question 44

what is an example of inverse agonists

Answer 44

antihistamines to H1 receptors

Question 45

competitive examples

Answer 45

ACEI, renin inhibitors, angiotensin

Question 46

non competitive examples

Answer 46

acetyl coa inhibitors, physostigmine, neostigmine, cyclooxygenase inhibition by aspirin, phenoxygenzamine,

Question 47

allosteric inhibitor examples

Answer 47

nonnucleotide reverse transcriptase inhibitors, antihistamines

Question 48

Pharmacokinetic agonists

Answer 48

reduced bioavailability of receptors

Question 49

What does potency mean

Answer 49

the concenttration or dose of a drug required to produce 50% of that drugs maximal effect

Question 50

Theraputic index

Answer 50

the ratio of TD-50 to ED-50

Question 51

Therapeutic window

Answer 51

the range between the minimum toxic dose and the minimum therapeutic dose.

Question 52

Idiosyncratic drug response:

Answer 52

unusual and infrequent response mostly due to generic factors