Pharmacodynamics

Question 1

pharmacodynamics

Answer 1

what the drug does to the body

Question 2

two concepts of pharmacodynamics

Answer 2

receptor activation & dose response

Question 3

four ways a drug can bring about an effect

Answer 3

1. drug/receptor complex=effect
2. drug/receptor complex=effector molecule=effect
3. drug/receptor complex=activation of coupling molecule=effector molecule=effect
4. drug/receptor complex=inhibition of endogenous activator metabolism=increased activator=increase effect

Question 4

receptor

Answer 4

a protein that binds a signaling molecule and in doing so generates a signal of its own

Question 5

constitutively active receptor

Answer 5

receptors that remain in active conformation even in absence of agonist binding

Question 6

agonist

Answer 6

a molecule that binds to and activates a receptor to bring about an effect

Question 7

full agonist

Answer 7

drug/agonist that saturates receptor pool, binds to active form, and stabilizes it so that large percent is in Ra-D form. brings about higher maximum response

Question 8

partial agonist

Answer 8

drug with low intrinsic activity. binds to Ra and stabilizes it so that a low % stays in Ra-D pool regardless of dose

Question 9

inverse agonist

Answer 9

drug has higher affinity for inactivated receptor and stabilizes large fraction of Ri-D pool. constitutive activity of receptor is lost

Question 10

antagonist

Answer 10

molecule that prevents activation of receptor by an agonist by binding to the active site. maintain same level as constitutive activity

Question 11

potency

Answer 11

concentration of drug required to achieve a certain effect (EC50: half of the maximum effect)

Question 12

efficacy

Answer 12

magnitude of the drugs action at the limit of its concentration (Emax, plateau)

Question 13

action of allosteric activator

Answer 13

amplifies agonist by binding to separate site on receptor. increases efficacy

Question 14

allosteric inhibitor

Answer 14

binds to separate site of receptor and cause conformational change that prevents agonist from binding or lowers its affinity once bound. changes the maximal response of the drug

Question 15

competitive inhibition

Answer 15

fights for binding site with agonist. causes reduction in response but ultimately drug still reaches maximal effect. can be overcome by increasing concentration of agonist

Question 16

dose response relationship

Answer 16

receptors largely determine the quantitative relationship between dose or concentration of drug and pharmacologic effect

Question 17

5 types of transmembrane signaling mechanisms

Answer 17

steroid receptors, cytokine receptors, receptor tyrosine kinase, ion channel, GCPRs

Question 18

steroid receptors

Answer 18

a lipid soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor

Question 19

cytokine receptors

Answer 19

signal binds to the EC domain of the receptor, activating the enzymatic activity of the cytoplasmic domain of the receptor (JAK STAT)

Question 20

receptor tyrosine kinase

Answer 20

signal binds to the EC domain of the receptor bound to a tyrosine kinase, which it then activates via phosphorylation

Question 21

ion channel

Answer 21

signal binds and directly regulates the channel’s opening. electrical potential of membrane is altered

Question 22

GCPRs

Answer 22

the signal binds to a cell surface receptor linked to an effector enzyme by a G protein

Question 23

mechanism of action of GCPR

Answer 23

extracellular ligand binds to cell surface receptor, receptor triggered activation of a G protein located on cytoplasmic face of plasma membrane, activated G protein changes activity of effector element, which changes the concentration of intracellular second messenger

Question 24

effector elements associated with GPCRs

Answer 24

adenylyl cyclase, ion channel, etc

Question 25

intracellular second messengers associated with GPCRs

Answer 25

cAMP, Ca2+

Question 26

Gs

Answer 26

associated with adenylyl cyclase. s=stimulation, increases levels of cAMP

Question 27

Gi

Answer 27

associated with adenylyl cyclase. i=inhibition, decreases levels of cAMP

Question 28

Gq

Answer 28

associated with phospholipid C (PLC-beta). stimulatory. increases intracellular calcium levels

Question 29

epinephrine receptor

Answer 29

beta adrenergic receptors increase cAMP via Gs

Question 30

acetylcholine receptor

Answer 30

muscarinic or nicotinic receptors decrease cAMP via Gi

Question 31

Gq associated with histamine in bronchiolar smooth muscle

Answer 31

associated with H1 receptor. increased Ca levels via PLC leads to vessel constriction

Question 32

Gs associated with epinephrine in bronchiolar smooth muscle

Answer 32

associated with B2 receptor. increases cAMP levels via adenylyl leading to vessel dilation

Question 33

TxA2 action in platelets

Answer 33

goes through Gq pathway in which increased Ca levels lead to platelet aggregation

Question 34

prostaglandin 2 (PGI2) action in platelets

Answer 34

goes through Gs pathway in which increased cAMP leads to disaggregation (relaxation)

Question 35

histamine via Gq

Answer 35

in bronchiolar smooth muscle cells. leads to contraction (anaphylaxis)

Question 36

histamine via Gs

Answer 36

in vascular smooth muscle cells. leads to relaxation/vasodilation

Question 37

GPCR downregulation

Answer 37

heterodimerization leading to endocytosis and then recycling or destruction

Question 38

GPCR desensitization

Answer 38

response to drugs/agonist diminishes over time.

Question 39

how does desensitization occur?

Answer 39

phosphorylation of the serene residues in the GPCR carboxyl tail recruits beta arrestin, which decreases receptor ability to interact with G protein subunit.

Question 40

is desensitization reversible/irreversible?

Answer 40

reversible following exposure to more agonist

Question 41

G protein structure

Answer 41

heterotrimeric (alpha, beta, gamma). dissociates upon ligand binding

Question 42

therapeutic leverage

Answer 42

can target drug action by synthesizing molecule to pick out a specific subtype of receptor

Question 43

graded dose response

Answer 43

with increasing dose, there is an increase in response

Question 44

quantal dose response

Answer 44

all or none dose response

Question 45

narrow therapeutic index

Answer 45

the difference between lethal dose and effective dose is small

Question 46

K3

Answer 46

measurement of a drugs intrinsic activity

Question 47

K3=1

Answer 47

drug is an agonist

Question 48

K3=0

Answer 48

drug is an antagonist

Question 49

1>K3>0

Answer 49

drug is a partial agonist

Question 50

threshold dose

Answer 50

the dose at which we start seeing a response to the drug

Question 51

Emax

Answer 51

the maximal effect of a drug. where it plateaus. if you add any more drug, no further effect will be seen, but toxicity will occur

Question 52

left shifted dose curve

Answer 52

indicative of higher potency

Question 53

competitive antagonist

Answer 53

involves receptors, completely reversible with increased agonist concentration

Question 54

noncompetitive antagonist

Answer 54

involved receptors, agonist fails to reverse it

Question 55

chemical antagonist

Answer 55

one drug binds to another drug, inactivating it or blocking its absorption

Question 56

physiologic antagonist

Answer 56

one drug does exactly the opposite of another drug and works on a different receptor

Question 57

ED50

Answer 57

the median dose required to have effects on 50% of people

Question 58

LD50

Answer 58

the median dose required to cause death in 50% of people

Question 59

therapeutic index formula (TI)

Answer 59

LD50/ED50

Question 60

what TI makes for a safe drug?

Answer 60

>10/15

Question 61

safety index

Answer 61

LD01/ED99