2.1 Pharm Exam1: Pharmacodynamics

Front 1

5 principles of Drug theory

Back 1

1. Bind specifically (receptor affinity)

2. Alter pathways (existing pathways)

3. Inhibit/Activate (physiological activity)

4. Compare basal (effectiveness)

5. Response proportional (to dose)

Front 2

Most drugs exist in a specific stereo-isomer & have a MW btwn ______ & ______ g/mole

Back 2

100 & 1000 g/mole

Front 3

list the following bonds from highest to lowest strength:

ionic, hydrogen, covalent, van der waals

Back 3

covalent

ionic

hydrogen

van der waals

Front 4

Binding affinity (KD) is a measure of how much of a drug is required to bind ____ of the receptors in a fixed population

Back 4

1/2

Front 5

The (higher/lower) the KD of a drug, the lower its affinity for the receptor

Back 5

higher

(bc it takes more of that drug to reach 1/2 saturation)

Front 6

How can KD (equilibrium disassociation constant) be calculated?

Back 6

at equilibrium:

KD= K1/K2 = [L][R]/[LR]

L + R --(K1)---> LR

L + R <--(K2)-- LR

Front 7

The receptor in this system has the greatest affinity for which of the drugs?

Back 7

Drug 2

(because it reaches 50% or 1/2 receptor saturation at lower concentration)

Front 8

Define efficacy

Back 8

the ability of the ligand (drug) (once bound to the receptor) to generated a biological response

(varies from 0-1)

(must have affinity to have efficacy)

Front 9

define

full agonist

Back 9

-substance that generates maximum biological response in a system, by activating 100% or less of the receptors

-affinity & efficacy = 1

Front 10

define

partial agonist

Back 10

-substance that produces less than the maximum achievable response, even when 100% of receptors are bound (only partially activate receptors)

-affinity & efficacy < 0 & > 1

Front 11

define

inverse agonist

Back 11

-substance that produces a decrease in the biological activity (from basal) (partially inactivates receptors)

Front 12

Allosteric agonists also increase the biological activity, how do they differ from other agonists?

Back 12

the do NOT bind to the agonist binding region, bind to another site & alter receptor conformation to increase efficacy or affinity for other substrates

Ex: Benzodiazepines for Ca2+ receptors

Front 13

define

chemical antagonist

Back 13

-substrate that binds to agonist & makes it inactive

Ex: chelator, used to treat metal poisoning by binding to Au, Hg, As, etc

Front 14

define

physiological antagonist

Back 14

-substrate that interacts on the same system as another agonist, independently & causes opposite effects

Ex: ach & epi have opposite effects on heart rate, are antagonists of one another, but do not interact

Front 15

define

indirect antagonist

Back 15

-substrate that inhibits a biological response by acting on a site beyond the receptor, agonist still acts on receptor but process is not completed

(usually inhibit agonists that act on multiple receptors)

Front 16

define

competitive antagonist

Back 16

-substrate that competes with agonist for binding site, prevents agonist binding & activation, have affinity but no efficacy

Front 17

Define

Equilibrium-competitive (reversible) antagonist

Back 17

-competitive antagonist that binds reversibly to the receptor

-antagonism CAN be overcome by increasing agonists

Front 18

Define

Nonequilibrium- Competitive (irreversible) antagonist

Back 18

-competitive antagonist that binds irreversible to the receptor via COVALENT bond

-antagonist CANNOT be overcome by increasing agonist

Front 19

define

allosteric antagonist

Back 19

-substrates that reduce the affinity &/or efficacy of agonists by binding to & altering a receptors conformation, do NOT bind to agonist binding region

Front 20

What is a graded response?

Back 20

One that changes proportionally w each dose of drug (agonist) given

-each single dose produces a single tissue response, curve is comprised of multiple responses generated separately by individual doses

Front 21

What is a quantal response?

Back 21

Response curves represents the "all or nothing" effect at different doses

-each dose produces a response in a certain percentage of test subjects, graph is made up using multiple doses of drug

Front 22

Potency compares the relative effectiveness of drugs that _______________, using ED50 values

Back 22

act by similar mechanisms ONLY

ED50= dose at which 50% maximum response is reached

Front 23

T/F

ED50 (potency) and KD (affinity) are directly related

Back 23

FALSE

Front 24

Which drug is more potent?

Back 24

Drug A

-has a lower ED50 dose

Front 25

Efficacy (KD) (or intrinsic activity) ranges btwn 0-1 for agonists & _____ for antagonists

Back 25

is 0 for antagonists

Front 26

Which drug is most potent?

Back 26

Drug A

(A & B have same max, but ED50 is lower for A)

Front 27

Which drug is a partial agonist?

Back 27

Drug C

-never reaches 100% response

Front 28

If drug B represents the normal curve, which drug represents a Reversible antagonist?

Back 28

Drug D

-Reversible antagonists cause a RIGHT shift = decrease in potency, while still allowing max response

Front 29

If drug B represents the normal curve, which drug represents an Irreversible antagonist?

Back 29

Drug C

-Irreversible antagonists cause a DECREASE in MAX response (indirect antagonist will cause same change in graph)

Front 30

What is the only way to reactivate receptors, when nonequillibrium-competitive/ irreversible antagonist has been used?

Back 30

via synthesis of new receptors

Front 31

What happens when you add a partial agonist along to a full agonist?

Back 31

partial agonist acts as an antagonist bc it takes receptors and has a lower efficacy than the full agonist attached receptors

(eventually outcompetes full agonist)

Front 32

________ receptors allow a max response to be achieved when only a small fraction (< 1/2) of receptors are occupied, even with a partial agonist

Back 32

spare receptors

Front 33

The fewer spare receptors present, the (more/less) receptors will need to be activated (by a full agonist) to reach maximal effect

Back 33

more receptors

Front 34

Most drugs act on (molecules essential to normal cell fxn/ enzymes/ DNA or molecules involved in specific intercellular communication)

Back 34

molecules involved in specific intercellular communications

Front 35

4 types of endogenous activators that act on 7-TMS G-Protein coupled receptors

Back 35

norepinephrine

serotonin

acetylcholine

histamine

Front 36

Norepinephrine activates what 7-TMS G-Protein coupled receptors?

Back 36

adrenergic receptors (alpha & beta)

Front 37

Serotonin acts on what receptors?

Back 37

serotonergice receptors (5-HT receptors)

Front 38

Acetylcholine acts on what receptors?

Back 38

muscarinic cholinergic receptors (M1, M2, M3, M4, M5)

Front 39

Histamine acts on what receptors?

Back 39

histamine receptors (H1 & H2)

Front 40

What are the 3 main Galpha subtypes?

Back 40

alphas, alphai, & alphaq/11

Front 41

What are the main effectors of as (alphas) ?

Back 41

-increase adenyl cyclase activity--> increase cAMP

Front 42

What are the main effectors of ai?

Back 42

-decrease adenyl cyclase--> decrease cAMP

Front 43

What are the main effectors of aq/11?

Back 43

-increase phospholipase C--> increase protein Kinase C, IP3, & Ca2+

Front 44

What are the as (a stimulatory) receptors?

Back 44

B1

B2

AR

glucagon receptor

Front 45

What are the ai (a inhibitory) receptors?

Back 45

a2

AR

uOR

Front 46

What are the aq/11 receptors?

Back 46

a1

AR

angiotensin

Front 47

Which 2 subtypes are physiological anatagonists?

Back 47

ai & as, act to antagonize each others actions (adenyl cyclase & cAMP, one is inhibitory while other stimulates)

Front 48

Desensitization, tachyphylaxis, tolerance, & adaption all lead to what?

Back 48

decrease in receptor activity due to long term dosing

Front 49

When chronic exposure leads to receptor down-regulation, the only way to increase effect is to ......

Back 49

resynthesize receptors

Front 50

Sensitization (super sensitivity) commonly occurs as a result of ___________

Back 50

receptor blockade removal

-causes more receptors to be made, then when removed there is an increase in receptors available = increased drug response

Front 51

_____________ receptors, such as nicotinic ach receptors & GABA receptors, act w/i miliseconds, & can be acted on by ____________ ligands

Back 51

Ionotropic receptors (ligand-gated ion channels)

ionic ligands (+ or -)

Front 52

___________ receptors, regulate transcription of genes involved in cell growth & differentation, act w/i minutes/hours/days & can be acted on by ________ ligands

Back 52

tyrosine-kinase receptors

cytoplasmic enzymes (tyrosine kinase, serine kinase, guanylate cyclase)

extracellular hormones (EGF, insulin, PDGF, ANF)= endogenous activators

Front 53

__________ receptors, such as JAK-STAT receptors, regulate genes involved in inflammation & hematoposis, act w/i hours/day & can be acted on by __________ ligands

Back 53

cytokine receptors

extracellular hormones (Growth Hormone, erythropoietin, interferon = endogenous activators

Front 54

___________ receptors, regulate gene transcription, act w/i hours/days & can be acted on by ____________ ligands

Back 54

intracellular receptors

hormone ligands: glucocortoids, mineralcorticoids, sex steriods, vit D, thyroid hormones = endogenous activators

Front 55

What is one property of ALL drugs that act as nuclear receptors?

Back 55

hydrophobic