Pharmacodynamics

Question 1

Definition of pharmacodynamics

Answer 1

effects of drugs on the body; drug receptors, dose-response curves, mechanisms of drug actions

Question 2

Definition of receptor

Answer 2

specific molecule in a biological system that plays a regulatory role

Question 3

Definition of ligand

Answer 3

molecule that binds to a receptor

Question 4

Emax

Answer 4

maximal effect that can be produced by drug

Question 5

ED50

Answer 5

dose of drug that produces 50% of its maximal effect

Question 6

Graded dose-response curve is used for…

Answer 6

measuring the magnitude of a response with given doses, typically represents the mean value within a population or single subject

Question 7

Quantal dose-response curve is used for…

Answer 7

determining if the “response” occurs, requires a pre-defined response

Question 8

Non-cumulative quantal dose response curve

Answer 8

number or % of individuals responding at a dose of a drug and only at that dose

Question 9

Cumulative quantal dose response curve

Answer 9

number or % of individuals responding at a dose of a drug AND at all doses lower than that dose

Question 10

TD50

Answer 10

median toxic dose

Question 11

LD50

Answer 11

median lethal dose

Question 12

Therapeutic index

Answer 12

TD50/ED50

Question 13

Therapeutic window definition

Answer 13

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

Question 14

Potency

Answer 14

describes amount of drug required to produce a specific pharmacological effect; represented by ED50

Question 15

Efficacy

Answer 15

maximal pharmacological effect a drug can produce, represented by Emax, related to total number of receptors available to bind a drug

Question 16

Parameters that describe the interaction of a drug with a receptor

Answer 16

binding, affinity, selectivity, intrinsic activity

Question 17

Covalent bond in drug-receptor binding

Answer 17

irreversible, requires drug removal and receptor activation requires re-synthesis of receptor or enzymatic removal of the drug

Question 18

Non-covalent bonds in drug-receptor binding

Answer 18

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

Question 19

Affinity

Answer 19

how readily and tightly the drug will bind to the receptor

Question 20

Bmax

Answer 20

maximal binding

Question 21

Kd

Answer 21

equilibrium dissociation constant, drug concentration at which 50% of the drug receptor binding sites are occupied by the drug

Question 22

Kd/affinity relationship

Answer 22

lower Kd, higher affinity; higher Kd, lower affinity

Question 23

selectivity

Answer 23

determined by its affinities at various binding sites

Question 24

Kd ratio

Answer 24

Kd, off target / Kd target

Question 25

Intrinsic activity

Answer 25

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

Question 26

Agonists

Answer 26

bind to receptor and stabilize it in a particular conformation, producing physiological response

Question 27

Antagonists

Answer 27

receptor antagonists bind to receptor but do not change its function, prevent activation of the receptor in the presence of an agonist

Question 28

Full agonist

Answer 28

fully activates receptors, produce a max pharmacological effect and has maximal intrinsic activity

Question 29

Partial agonists

Answer 29

partially activate the receptor, producing a sub-max effect

Question 30

Inverse agonist

Answer 30

produce an effect opposite to a full or partial agonist, decreases receptor signaling and response at receptors with a significant level of constitutive receptor activity

Question 31

Pharmacologic antagonism

Answer 31

action at the same receptor as endogenous ligands or agonist drugs

Question 32

Chemical antagonism

Answer 32

when chemical antagonist makes the other drug unavailable

Question 33

Physiologic antagonism

Answer 33

occurs between endogenous pathways regulated by different receptors

Question 34

Competitive antagonists

Answer 34

compete with endogenous chemicals or agonist drugs for binding receptor, can be displaced

Question 35

Non-competitive antagonists

Answer 35

irreversible or allosteric receptor inactivation

Question 36

Irreversible antagonists

Answer 36

irreversibly bind to and occlude agonist site on receptor by forming covalent bonds

Question 37

Allosteric antagonists

Answer 37

bind to a site other than the agonist site to prevent or reduce agonist binding or activation of receptor

Question 38

EC50 / Emax relationship in competitive antagonism

Answer 38

agonist EC50 increases, Emax does not change

Question 39

Emax / EC50 relationship in noncompetitive antagonism

Answer 39

agonist Emax decreases, EC50 does not change

Question 40

Signal transduction definition

Answer 40

process by which cells transmit, receive, and respond to info from their environment and from each other

Question 41

Steps of GPCR activation

Answer 41

1. GPCR receives ligand 2. Agonist activates receptor 3. GDP release from Ga protein 4. GTP enters into nt binding site 5. G protein regulates activity of an effector enzyme or ion channel 6. GTP hydrolysis and return to steady state

Question 42

Gs activation result

Answer 42

adenylyl cyclases activated

Question 43

Gi activation result

Answer 43

adenylyl cyclases inhibited

Question 44

Gq activation result

Answer 44

PLC activation

Question 45

G12/13 activation result

Answer 45

Rho GTPases resulting in cytoskeletal rearrangements

Question 46

cAMP second messenger pathway

Answer 46

Gs protein activates adenylyl cyclase and produces cAMP (hydrolyzed by PDE). Phosphorylated protein subunit produces a response

Question 47

DAG/IP3 signaling

Answer 47

G protein activates PLC which splits PIP2 into DAG and IP3. Ca-CaM complex forms and creates a response along with the phosphorylated protein substrate

Question 48

JAK-STAT path overview

Answer 48

Cytokine binds to JAK, resulting in phosphorylation of STAT molecules. STAT dimers travel to nucleus and regulate transcription

Question 49

JAK-STAT common cytokines

Answer 49

EPO, leptin, GH, leptin, Interferons, IL-2 to 10 and 15

Question 50

RTK pathway overview

Answer 50

cytokine binds and converts RTK to active dimeric state, auto-phosphorylate tyrosine residues which catalyzes the phosphorylation of other substrates, such as RAS GTPase

Question 51

RTK common cytokines

Answer 51

IGF-1, Insulin, VEGF, EGF, NGF, PDGF

Question 52

Mutations in Ras proteins are most common in which types of cancer

Answer 52

pancreatic adenocarcinomas

Question 53

Mutations in Raf proteins are most common in which types of cancer

Answer 53

melanomas

Question 54

Nuclear receptors

Answer 54

ligand-activated transcription factors that modulate gene activity, ligands are lipophilic molecules that are able to cross the cell membrane

Question 55

Common ligands for nuclear receptors

Answer 55

lipophilic molecules, steroid hormones, thyroid hormones, Vitamins D and A, lipid mediators