Pharm Ii (Mod, Test #1) Set 3

Front 1

What are two receptor signaling mechanisms?

Back 1

1. Conformational change in the receptor (eg, ligand-gated receptor)
2. Activation of one or more biochemical pathways within the cell

Front 2

What has to occur for the conformational change in the receptor?

Back 2

Agonist (ligand) binds to cell membrane receptor and causes and ion channel to open within the receptor

Front 3

What are examples of receptors that have conformational changes?

Back 3

Nicotinic ACh receptor and GABA receptor

Front 4

What are two ways activation of one or more biochemical pathways occurs?

Back 4

1. Intracellular receptors
2. G-proteins and second messengers

Front 5

Intracellular receptors,the agonist is? the receptor is?

Back 5

agonist is lipid soluble; receptor is in the cytosol or cell nucleus

Front 6

What is an example of an intracellular receptor?

Back 6

Ex: steroids bind to intracellular receptors (glucocorticoid receptor), which then bind to DNA sequences in the cell nucleus and stimulate gene transcription

Front 7

Describe the agonist in G-proteins and second messengers

Back 7

many agonists act by increasing the intracellular concentrations of second messengers, which, in turn, cause the cellular response to the agonist

Front 8

Describe the receptor in G-proteins and second messengers

Back 8

the receptor is a transmembrane protein; the extracellular domain of receptor binds the agonist; this, in turn, causes activation of a G-protein on the cytoplasmic surface of the cell membrane (so called b/c the protein is activated by the binding of GTP)

Front 9

What does the activated G-protein then do?

Back 9

alters the activity of some intracellular effector, usually an enzyme or an ion channel

Front 10

What are some examples of G proteins?

Back 10

Gs, Gq, Gi

Front 11

What are some examples of second messengers?

Back 11

cyclic AMP (cAMP), cyclic GMP (cGMP), inositol triphosphate (IP3), calcium

Front 12

Cell receptor concentrations are in a?

Back 12

dynamic state, responsive to both endogenous and exogenous factors

Front 13

Down-regulation

Back 13

reduction in receptor concentration, ie, due to repeated or prolonged exposure of cells to excess agonist; may result in drug TOLERANCE

Front 14

Up-regulation

Back 14

increases in receptor concentration, ie, due to prolonged exposure of cells to an antagonist; can result in hyperresponsiveness ("overshoot") to agonist when the antagonist is abruptly withdrawn

Front 15

Dose-response curve is the quantitative relation between?

Back 15

drug dose (concentration) and drug response

Front 16

This dose-response curve is?

Back 16

a hyperbolic curve; resembles curve that describes the interaction between a ligand and a receptor

Front 17

If drug effect is plotted against the LOGARITHM of drug dose or concentration, the resulting curve is?

Back 17

sigmoidal (S-shaped) and has a linear midportion; this approach is very useful for comparison of dose-response curves for different drugs

Front 18

Potency is located on the curve along the ______ axis?

Back 18

dose (more to left=more potent)

Front 19

Potency is determined by?

Back 19

the binding affinity of receptors for the drug as well as the efficiency of coupling of binding to response

Front 20

Potency is the _______ potency of drugs

Back 20

relative

Front 21

Slope relationship between

Back 21

change dose and change effect

Front 22

Steep slope means

Back 22

that small increases in drug concentration result in large increases in drug effect

Front 23

Efficacy

Back 23

maximal drug effect -- reflected by the plateau of dose-response curve

Front 24

Efficacy is probably more important than?

Back 24

potency when deciding which drug to administer

Front 25

Are efficacy and potency related?

Back 25

no

Front 26

Variability is found within a given individual and between individuals, may reflect differences in?

Back 26

pharmacokinetics (absorption, distribution, clearance) and/or differences in pharmacodynamics (receptor responsiveness, drug concentration)

Front 27

drug responses are influenced by?

Back 27

bioavailability, renal function, hepatic function, cardiac function, and age

Front 28

Competitive antagonists shift the curve to the?

Back 28

right; agonist efficacy is not reduced

Front 29

Noncompetitive antagonists shift the curve?

Back 29

down (reduced efficacy) and to the right

Front 30

Median effective dose (ED50)

Back 30

the dose at which 50% of individuals exhibit a specified, or quantal, drug effect

Front 31

Can ED50 be different for different drug actions?

Back 31

Yes, ex: the ED50 for aspirin effect to relieve headache is less than the ED50 to relieve pain of arthritis

Front 32

Median toxic dose (TD50)

Back 32

dose of drug required to produce a particular toxic effect in 50% of animals

Front 33

Median lethal dose (LD50)

Back 33

is used if the toxic effect is defined as death

Front 34

Therapeutic index (TI)

Back 34

TD50/ED50 "margin of safety," want the ratio as high as possible

Front 35

What are 4 examples of drug effects not mediated by receptors?

Back 35

1. Enzyme inhibition, eg, MAO inhibitors
2. Enzyme activation
3. Direct membrane effects
4. Antacids: buffer gastric acid

Front 36

What is an example of a drug with enzyme activation?

Back 36

nitric oxide (NO) activates the cytosolic enzyme guanylyl cyclase to produce cyclic GMP (cGMP) ---> smooth muscle relaxation

Front 37

Which drugs have direct membrane effects?

Back 37

inhalational anesthetics

Front 38

Drug interactions

Back 38

one drug alters the intensity of the effects of another drug administered at the same time

Front 39

What are possible net results of drug interactions?

Back 39

may be enhanced or diminished effects of one or both of the drugs

Front 40

Pharmacokinetic interactions

Back 40

one drug alters the absorption, distribution, or clearance of another drug

Front 41

Pharmacodynamic interactions

Back 41

one drug alters the drug-receptor interaction of another drug

Front 42

Interactions can be?

Back 42

beneficial or adverse

Front 43

Additive effect

Back 43

total pharmacological effect of two drugs is the algebraic sum of the individual effects of the drugs

Front 44

Synergistic effect

Back 44

two drugs interact to produce a pharmacological effect which is greater than the sum of the individual effects

Front 45

Gs protein are receptors for? What is the effector/signaling pathway?

Back 45

beta-adrenergic amines
Increased adenylyl cyclase ---> increased cAMP

Front 46

Gi1, 2, 3 are receptors for? What is the effector/signaling pathway?

Back 46

alpha2-adrenergic amines, acetylcholine (muscarinic), opioids
Decreased adenylyl cyclase --> decrease cAMP

Front 47

Gq are receptors for? Effector/signaling pathway?

Back 47

acetylcholine (muscarinic)
Increase phospholipase C --> IP3 (2nd messenger, mobilizes Ca in cell causing a response)