Module A-1

Question 1

Signal Transduction

Answer 1

Process by which a cell converts one kind of signal into another, think signal cascade or second messenger pathway

Question 2

Types of signal Transduction:

Answer 2

Ion Channel- think acetylcholine as ligand for receptor vs voltage gated
G-coupled protein receptor-spans 7 times, w/ three subunits-conformational change with GDP-GTP
Enzyme linked-Ex. tyrosine kinase-signal molecule triggers dimerization/phosphorylation of residues with starts cascade

Question 3

GPCR Ex.

Answer 3

Question 4

Drug receptor Sensitivity

Answer 4

Drug response occurs from a low concentration

Question 5

Drug receptor selectivity

Answer 5

Structurally similar chemicals illicit drug response

Question 6

Drug receptor Specificity

Answer 6

Measure of a receptors ability to respond to a single ligand

Question 7

Affinity VS. Potency

Answer 7

Affinity-strength of attraction
Potency-magnitude of drug effect (dose dependent)

Question 8

Agonist

Answer 8

Binds specific receptor and triggers a response in a cell-mimics an endogenous ligand

Question 9

Agonist

Answer 9

Binds specific receptor and triggers a response in a cell-mimics an endogenous ligand

Question 10

Antagonist

Answer 10

Affinity for receptor but no efficacy

Question 11

Partial agonist

Answer 11

Activates receptor but cannot produce maximum response- may also block full effect of true agonist

Question 12

Inverse Agonist

Answer 12

Binds receptor-results in opposite action of agonist

Question 13

Non competitive antagonism

Answer 13

Binds allosteric site- cannot be displaced

Question 14

Allosteric modulators

Answer 14

Binding site adjacent/separate from receptor- can be agonist or antagonist!!

Question 15

Two state model

Answer 15

Constant flux in equilibrium between resting and active states that are conformationally distinct- active state has a higher affinity for an agonist

Question 16

Upregulation

Answer 16

An increase in number/sensitivity of receptors

In response to:
-less stimulation from ligands
-chronic antagonist exposure
Ex. Chronic use of beta adrenergic antagonists (Beta blockers)- rebound hypertension if stopped due to upregulation

Question 17

Down regulation

Answer 17

Decrease in number/sensitivity of receptors due to:
-Repeated agonist exposure

Ex. Chronic beta-agonist use for asthma
-increase dose (side affects) or swap drugs

Question 18

Tolerance

Answer 18

Chronic exposure- increased drug clearance. increasing dose is usually an option

Question 19

Tachyphylaxis

Answer 19

Short term- stepwise reduction in physiological response due to down regulation of receptors-which means increasing the dose will not work

Question 20

Therapeutic response variation with pharmacogenetics and population variation

Answer 20

-age, sex, BSA, weight, metabolic rate, pathological state and genetic profile will all impact therapeutic response

Pharmacogenetics can alter receptor sensitivity and drug metabolism between individuals

Question 21

Mean

Answer 21

Average dose to elicit a response

Question 22

Median

Answer 22

Dose on either side of which half the responses occur

Question 23

Mode

Answer 23

Dose with greatest percentage of responses

Question 24

Standard deviation

Answer 24

Variability of a response within a population

Question 25

Standard error of the mean

Answer 25

SD of the mean Obtaining the mean on different populations with same dose response measurements….

Question 26

ED-50

Answer 26

Median effective dose

Question 27

ED95

Answer 27

95% effective dose

Question 28

Emax

Answer 28

Maximal drug effect

Question 29

LD50

Answer 29

Lethal dose 50%

Question 30

Therapeutic index

Answer 30

LD50/ED50 Therapeutic Saftey margin Larger the index the safer the drug (how far apart are the ED and LD)

Question 31

Therapeutic window

Answer 31

The range of therapeutically effective concentrations, most of the efficacy curve and less than 10% of toxicity curve

Question 32

Addition

Answer 32

1+1=2 Drugs act in same pathway Sulfamethoxazole+trimethoprim

Question 33

Synergism

Answer 33

1+1=4 One drug allows the other to perform its function Ex. Carbidopa+levodopa (keeps levodopa from being degraded in peripheral tissue)

Question 34

Antagonism example:

Answer 34

Phentolamine displaces Norepinephrine

Question 35

What increases the tendency to form the drug-receptor complex?

Answer 35

Higher concentration of free drug Presence of unoccupied receptor

Question 36

Law of mass action

Answer 36

Rate of a reaction is proportional to the product of the concentrations of each reactant

Question 37

Second messengers and response to: Catecholamines, caffeine and milrinone

Answer 37

(cAMP) Response: kinase release, beta receptor stimulation, inotropic and chronotropic cardiac effects, production of adrenal and sex steroids, etc…

Question 38

Second messengers and response to Lithium

Answer 38

Phosphoinositides and Calcium Activates calmodulin

Question 39

Nitroglycerin and Nitroprusside second messengers

Answer 39

cGMP Activates protein kinases

Question 40

Fig 5.1-major modes of signal transduction

Answer 40

Question 41

Potentiation

Answer 41

Effect of a drug is enhanced by a drug with no effect of its own 1+0=3

Question 42

Chiral

Answer 42

Not superimposable on its mirror image, optically active

Question 43

Stereoisomer

Answer 43

Isomers that differ in the 3-D dimensional arrangement of atoms

Question 44

Enantiomer

Answer 44

Stereoisomers that are non-superimposable

Question 45

Racemic mixture

Answer 45

A mixture containing two enantiomers in equal proportions will be optically inactive, Enantiomers can differ in dosages/efficacy/side effects but are sometimes given in racemic form

Question 46

Specificity vs selectivity phrase

Answer 46

Select chemicals illicit a specific response

Question 47

Describe GPCR second messenger system

Answer 47

Question 48

Describe GPCR second messenger system

Answer 48