Di Cera Leture (Pharmacology Block One)

Front 1

1) Define pharmacology
2) Define Medical Pharmacology

Back 1

1)The study of substances that interact with living systems through chemical processes

2)Study of substances used to prevent, diagnose, or treat disease

Front 2

Define Toxicology

Back 2

The branch of pharmacology which deals with the undesirable effects of chemicals on living systems

Front 3

Define Pharmacogenomics

Back 3

relation of the individual’s genetic make-up to his/her response to specific drugs

Front 4

Define "Drug"

Back 4

Substnce which brings about a change in biological function through chemical actions at a receptor

Front 5

Define Hormone

Back 5

Drug synthesized within the body

Front 6

Define poison

Back 6

Drugs that have almost exclusively harmful effects.

Front 7

Define Toxin

Back 7

poisons of biological origin (from plants or animals)

Front 8

Define Xenobiotic

Back 8

Drugs not synthesized in the body

Front 9

1) Optimal drug size is MW= ?
2) Why bad if too low?
3) why bad if too high?

Back 9

1) 0.1 - 1 kD
2) may not be specific enough
3) problems with diffusion

Front 10

Which type of drug-receptor bond is ALWAYS short range and is mainly responsible for controlling dissociation and specificity?

Back 10

Hydrophobic (Van der Wall)

Front 11

Why is SC-558 (approx =Celebrex) selective for COX-2.

Back 11

The additional steric interaction of the drug Sulphonamide moiety with Ile (COX-1) over Val (Cox-2) blocks binding of SC-558 to COX1

Front 12

Argatroban is an inhibitor of?

Back 12

Thrombin

Front 13

1) k1 (association constant) is limited by?

2) what factors influence this limit?

Back 13

limited by diffusion to 6.5 108 M-1s-1

influenced by dimensionality, electrostatics, solution conditions

Front 14

Specificity is mainly controlled by which kinetic parameter?

Back 14

k-1 ( dissociation constant)

Front 15

k-1 is limited by?

Back 15

No upper limit

Front 16

How does the rate of equilibration of a system (L, R, and RL) relate to the timescales of the dissociation and dissociation?

Back 16

Equilibrium is always reached faster than the fastest time scale

Front 17

How do we calculate a:
1) Association time constant (tau)?
2) Dissociation time constant (tau)?

Back 17

1) 1 / (k1 x [L])
2) 1 / k-1

Front 18

1)Define Kd and give it's units.
2) describe what higher and lower values mean in terms of affinity.

Back 18

Kd (M) is the equlibrium dissociation constant which is the concentration of FREE ligand when the receptor is 50% occupied,

2) The lower the Kd, the higher the affinity.

Front 19

Ka is the association constant.
1) What are its units?
2) A higher Ka means what in terms of affinity?

Back 19

1) 1/M

2) higher Ka means higher affinity.

Front 20

Give another way to mathematically represent Kd

Back 20

[L]50

Front 21

Given another way to represent [RL]50

Back 21

[R0] / 2

Front 22

The more negative the Delta H the ________ the affinity of L for R

Back 22

Higher

Front 23

The more _________ the delta S, the higher the affinity of L for R

Back 23

positive

Front 24

Each tenfold increase in __1___ decreases Delta G by ____2____

Back 24

1) Ka
2) 1.4 kcal/mol at 37C

Front 25

delta H greater than zero means ____thermic

Back 25

endothermic

Front 26

Define induced fit

Back 26

When R binds L, a conformational change occurs
such that RL goes to R*L.
R* and L have a greater affinity than R and L. Affinity is enhanced over initial step of recognition

Front 27

Selective binding

Back 27

you know this, it is the thing where R is in an eq with R* and L bind R* to drive the equilibrium in a LeChatelier kind of way.

Front 28

Define Allosteric binding

Back 28

L binds preferentially (not exclusively) to one conformation
affinity is decreased or increased relative to the step of recognition

Front 29

1)Define Kcat
2) give its units

Back 29

1) turn over ate

2) 1/s (per second)

Front 30

1) Define Km
2) give its units

Back 30

1) [S] at half Vmax
2) Molar

Front 31

1) What is the specificity constant?
2) units?
3) what limits it?

Back 31

1) Kcat/Km
2) M-1s-1
3) diffusion

Front 32

Lineweaver Burk plot:
1) x-int = ?
2) y-int = ?
3) slope = ?
4) units of x-axis?

Back 32

1) -1/Km
2) 1/Vmax
3) Km/Vmax
4) 1/[S]
5) 1/Vo

Front 33

Competitive inhibition
1) Change in Vmax?
2) Change in Km?
3) define

Back 33

1) no
2) increase
3) I binds only to E

Front 34

Un-competitive inhibition:
1) Change in Vmax?
2) Change in Km?
3) define

Back 34

1) Decrease
2) Decrease (proportional)
3) I binds only to ES

Front 35

Non-competitive Inhibition
1) Change in Vmax?
2) Change in Km?
3) define

Back 35

1) Decrease
2) same
3) I binds to E or ES

Front 36

Give an alternate way to describe Kcat

Back 36

k for ES to E +P

Front 37

1) define Tight binding inhibition
2) slope of T vs. [P] curve goes to?

Back 37

1) inhibitor binding /dissociation rates are slow
2) constant positive slope

Front 38

1) define Irreversible inhibition
2) slope of T vs. [P] curve goes to?

Back 38

1) inhibitor will not release E
2) slope goes to zero

Front 39

what kind of inhibitor

Back 39

competitive

Front 40

what kind of inhibitor

Back 40

competitive
Vmax same
Km increase

Front 41

what kind of inhibitor?

Back 41

competitive
Vmax same
Km increase

Front 42

what kind of inhibitor?

Back 42

irreversible

Front 43

what kind of inhibitor?

Back 43

non-competitive
Km same
Vmax Decreases

Front 44

what kind of inhibitor?

Back 44

non-competitive
Km same
Vmax Decreases

Front 45

what kind of inhibitor?

Back 45

tight-binding

Front 46

what kind of inhibitor?

Back 46

uncompetitive
Km and Vmax both decrease

Front 47

what kind of inhibitor?

Back 47

uncompetitive
Km and Vmax both decrease