Pharmacodynamics (Konorev)

Question 1

Define pharmacodynamics

Answer 1

effects of drugs on the body including:

• drug receptors
• dose-response curves
• mechanisms of drug actions

Question 2

Define receptor vs. ligand in regards to pharmacology

Answer 2

receptor: a specific molecule in a biological system that plays a regulatory role. Receptor interacts with a drug and initiates the biochemical events leading to drug effects

ligand: it is a molecule like a hormone or drug which binds to a receptor

Question 3

What is a dose-response curve

Answer 3

the relationship between a drug and its effects is described quantitatively using a dose-response curve

when you plot drug dose arithmetically on the x-axis vs. drug effect on the y-axis you typically get what is called a hyperbolic curve

Question 4

How is a concentration-effect curve commonly presented?

Answer 4

by graphing the logarithm of the drug dose vs. the response in which case you get a sigmoidal curve

Question 5

Define Emax

Define ED50

Answer 5

Emax is teh maxmial effect that can be produced by the drug

ED50 is the effective dose 50 or the dose of the drug that produces 50% of its maximal effect

Question 6

What is a graded response (curve)?

Answer 6

Answers: How Much?

• Magnitude of a response varies continuously
• typically represents the mean value within a population or a single subject

Question 7

What is the quantal dose-response (curve)?

Answer 7

All or none, yes/no binary responses

answers the question: Does the response? occur, or how many?

• requires a pre-defined response
• used to examine the frequency of a response within a large population

Question 8

What is a non-cumulative quantal dose response curve?

Answer 8

Number of % of individuals responding at a dose of a drug and only at that dose

Question 9

What is a cumulative quantal dose response curve?

Answer 9

Number of % of individuals responding at a dose of a drug and at all doses lower than that dose

Question 10

Define:

ED50

TD50

LD50

Answer 10

ED50: median effective dose

TD50: median toxic dose

LD50: median lethal dose

Question 11

Drug safety index can be described by the therapeutic index

Answer 11

TI=TD50/ED50 (the higher the TI, the safer the drug)

Question 12

What is the therapeutic window?

Answer 12

the range of doses of a drug or of its concentration in a bodily system that provides for the safe and effective therapy

Question 13

Define drug potency

Answer 13

describes the amount of drug required to produce a specific pharmacological effect

• Describes the amount of a drug required to produce a specific effect
• represented by the ED50
• the lower the ED50, the more potent the drug
• determines the drug dose to be used clinically

Question 14

Define drug efficacy

Answer 14

describes the maximal pharmacological effect that a drug can produce

• represented by the Emax
• the greater the Emax, the more efficacious the drug
• efficacy is related to the total number of receptors available to bind a drug
• determines the magnitude of clinical effect

Question 15

What are the four ways a drug can interact with its receptor?

Answer 15

binding

affinity

selectivity

intrinsic activity

Question 16

Describe covalent drug-receptor binding

Answer 16

irreversible, requires resynthesis of the receptor or enzymatic removal of the drug

Question 17

Describe non-covalent drug-receptor binding

Answer 17

reversible, most drugs bind to receptors via non-covalent bonds

Question 18

Describe affinity of a drug for a receptor

Answer 18

The affinity of a drug for its receptor describes how readily and tightly that drug binds to its receptor

• high affinity: strong drug-receptor interaction, less drug needed to produce a response
• low affinity: poor drug receptor interaction; more drug needed to produce a response

Question 19

What is Kd?

Answer 19

describes affinity

drug concentration at which 50% of the drug receptor binding sites are occupied by the drug

unit is in molar concentrations

lower Kd indicates higher affinity for receptor

higher Kd indicates lower affinity of a drug for a receptor

Question 20

Describe drug selectivity

Answer 20

Selectivity is a property of a drug determined by its affinities at various binding sites

measured by comparing affinities of a drug to different receptors

a more selective drug would have higher Kd ratio and affect fewer targets over a specific concentration range

Question 21

How does selectivity relate to adverse effects

Answer 21

more selective drugs have fewer adverse effects

less selective drugs have more adverse effects

Question 22

What is Intrinsic activity?

Answer 22

intrinsic activity describes the ability of a drug to change a receptor function and produce a physiological response upon its binding to a receptor

Question 23

What is an agonist?

Does it have intrinsic activity?

Answer 23

an agonist binds to the receptor and stabilize it in a particular conformation, producing a physiological response

Has intrinsic activity

Question 24

What is an antagonist?

Does it have intrinsic activity?

Answer 24

A receptor antagonist binds to the receptor but do no change its function. They prevent activation of the receptor in the presence of an agonist

Does not have intrinsic activity

Question 25

What is a full agonist?

Answer 25

Fully activate receptors produce a maximal pharmacological effect when all receptors are occupied maximal intrinsic activity

Question 26

What is a partial agonist?

Answer 26

partially activate the receptor upon binding produce a sub-maximal pharmacological effect when all receptors are occupied intrinsic efficacy caries depending on drug, but is always submaximal

Question 27

What is an inverse agonist?

Answer 27

produces an effect opposite to a full or partial agonist * decreases receptor signaling * decreases response at receptors with a significant level of constitutive receptor activity * intrinsic activity is present and related to the inhibition of receptor function

Question 28

What is pharmacologic (receptor) antagonism?

Answer 28

action at the same receptor as endogenous ligands or agonist drugs

Question 29

What is chemical antagonism?

Answer 29

When chemical antagonist makes the other drug unavailable

Question 30

What is physiologic antagonism?

Answer 30

occurs between endogenous pathways regulated by different receptors

Question 31

What are competitive antagonists?

Answer 31

* compete with endogenous chemicals or agonist drugs for binding the receptor * can be displaced from the receptor by other drugs (effects are surmountable)

Question 32

What are non-competitive antagonists?

Answer 32

* receptor inactivation is not surmountable * **irreversible antagonists**: irreversibly bind to and occlude the agonist site on the receptor by forming covalent bonds * **allosteric antagonists**: bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor

Question 33

How does EC50 and Emax change in competitive antagonism?

Answer 33

Agonist EC50 increases Emax does not change

Question 34

How does Emax and EC50 change in noncompetitive antagonism?

Answer 34

EC50 does not change Agonist Emax decreases

Question 35

How do full agonists work?

Answer 35

mimic actions of endogenous chemicals at receptors example: activation of mu opioid receptors by opioid analgesics such as morphine and codeine

Question 36

How to antagonists, partial and inverse agonists, work?

Answer 36

block the actions of endogenous lignads at receptors example: blockade of the a1 adrenoceptors receptors by the antihypertensive drug, prazosin

Question 37

What are the major classes of drug targets?

Answer 37

membrane receptors nuclear receptors ion channels transport proteins enzymes drugs are designed to target important regulatory proteins in the existing cell signaling pathways

Question 38

G protein families:

Answer 38

Gs-AC activation Gi-AC inhibition Gq-PLC activation G12/13-Rho GTPases, cytoskeletal rearrangements

Question 39

GPCR signaling cascades are either

Answer 39

cyclic AMP second messenger pathway lead or DAg/IP3 lead

Question 40

JAKs transmit the effect of a number of hormones and cytokines to activate the JAK-STAT pathway including

Answer 40

growth hormone (somatotropin) erythropoietin letpin itnerferons interleukins 1-10, 15

Question 41

RTKs transmit the action of growth factors such as

Answer 41

IGF-1 insulin VEGF EGF NGF PDGF

Question 42

RTK signaling pathways as drug targets for oncogenes in growth factor pathways including

Answer 42

overexpression or amplifications of GF point mutations or amplifications of GF receptors point mutations in RAS point mutations in Raf targeted anticancer drugs inhibit upregulated growth factor signalging

Question 43

nuclear receptors are ligand-activated transcription factors that modulate gene expression

Answer 43

ligands are lipophilic molecules that are able to cross cell membranes including steroids and thyroid hormones vitamines A and D lipid mediators

Question 44

Ion channels as drug targets used for

Answer 44

maintaining resting membrane potential shape action potentials change the concentration of ions in cytosol (used for arrythmias, angina pectoris, hypertension, constipation)