Pharm I Receptors

Front 1

For receptor time-response, place the following in order of response: G-protein, Ion channel, Enzyme linked , DNA transcriptional contol (milisec, sec, min, hours)

Back 1

milisec: ion channel… Seconds: G-protein… Minutes: Enzyme Linked… Hours: DNA transcriptional control

Front 2

Give the equation for the binding affinity constant: Ka

Back 2

Ka = k1/k2

Front 3

Give the equation for the dissociation constant: Kd

Back 3

Kd = k2/k1 = [D][R]/[DR]

Front 4

When 50% of receptors are bound, what is the value of [R] (receptors)? And what is the value of Kd?

Back 4

Given that Kd = [D][R]/[DR]… At 50% receptor saturation, [R]=[DR]… thus Kd=[D]

Front 5

If Kd is low, what is the receptor/drug affinity?

Back 5

High

Front 6

If the Kd is high, what is the receptor/drug affinity?

Back 6

Low

Front 7

Give the formula for determining the amount of bound drug to receptors

Back 7

B=(Bmax X [D])÷(Kd + [D])

Front 8

Given the fomula for BOUND DRUG:

B=(Bmax X [D])÷(Kd + [D])

Define B, Bmax, [D] and KD

Back 8

For B=(Bmax X [D])÷(Kd + [D])

B is the amount of bound drug…

Bmax is the maximum amount of specific binding sites
[D] is the amount of free drug at equilibrium

Kd is the equilibrium dissociation constant

Hint 8

None

Front 9

When does the Kd = [D]?

Back 9

when 50% of the receptors are bound to drug

Front 10

Given a saturation for curve specific binding that shows Bmax (and 1/2-Bmax), how do you determine the equilibrium constant (KD)?

Back 10

KD is found along the X-axis where Bmax = 50%

Hint 10

None

Front 11

What does EC50 represent?

Back 11

EC50= [D] when 50% of the max effect (Emax) is seen...

Or

EC50 is the [drug] that produces half of the maximal effect

Hint 11

None

Front 12

Are Kd and EC50 the same?

Back 12

not necessarily

Front 13

What does Kd represent?

Back 13

Given that Kd=[R][D]÷[DR]

Kd determines the fraction of receptors bound to Drug at a given [D], independent of the [B].

Hint 13

None

Front 14

Which cannot be saturated by excess drug, specific binding or non-specific binding?

Back 14

non specific binding

Hint 14

None

Front 15

How do you determine the number of specific binding, given the total number of binding and the total number of non-specific binding?

Back 15

Specific Binding = total binding - non-specific binding

Front 16

What does cell sensitivity to drug dependent upon?

Back 16

Affinity (Kd) and degree of spareness

Front 17

Give the formula for the effect of a drug and define the terms: E =?

Back 17

Effect of a drug:

E=(Emax x [D])÷ (EC50 + [D]

where Emax is the maximum effect of a drug at highest concentration…

[D] is the concentration of free drug…

EC50 is is the concentration of drug that produces 1/2 of the maximum effect

Hint 17

None

Front 18

Given a graph that shows the maximum effect of a drug at highest concentration (Emax) and 50% of Emax, where would you determine EC50? (the concentration that produces 1/2 of the maximum effect)

Back 18

EC50 is the point along the X-axis where Emax is at 50%

Front 19

how can the maximal biological effect of a drug occur with only a fraction of receptors being occupied?

Back 19

Spare receptors

Front 20

how is it that spare receptors increase the sensitivity of a receptor to its ligand?

Back 20

there is a greater likelihood of the ligand binding with more receptors, therefore, since there is an excess of receptors, activation requires less ligand (drug)

Front 21

What is an antagonist?

Back 21

binds to receptor but does not produce a response

Front 22

How would you reverse the effects of a competitive antagonist?

Back 22

apply a higher concentration of agonist so as to out-compete the antagonist

Front 23

What is a non-competitive antagonist?

Back 23

Cannot be reversed by any concentration of agonist

Front 24

Is an irreversible antagonist always non-competitive?

Back 24

yes

Front 25

Is a non-competitive antagonist always irreversible?

Back 25

No

Front 26

Graphically, which antagonist resembles a partial agonist? A competitive or non-competitive antagonist?

Back 26

graphically, a non-competitive antagonist resembles a partial agonist, because in both cases the full effect cannot be attained regardless of how much agonist is applied

Front 27

If a receptor without a drug is mostly in an inactive state and a receptor that is bound to an agonist is mostly in an active state, what state is a partial agonist in?

Back 27

only partially active

Front 28

what is a partial agonist?

Back 28

bind and produces response , but not = in response to full agonist

Front 29

What does a partial agonist look like on a graph?

Back 29

like an agonist combined with an non-competitive antagonist

Hint 29

None

Front 30

what affect does a partial agonist have on a full agonist?

Back 30

act somewhat like a non-competitive antagonist

Hint 30

None

Front 31

What is an inverse agonist?

Back 31

Inverse agonists stablize a receptor in its "off" state: So it binds to a receptor and produces a response that is opposite to an agonist

Front 32

Of the following, (parial agonist, antagonist, inverse agonist)which will have the greatest NEGATIVE affect on a circuit that is on (due to an agonist)? (Hint: place in order)

Back 32

Greatest to lowest negative effect: inverse agonist > antagonist > partial agonist

Front 33

Of the following, (partial agonist, agonist, inverse agonist), which will have the most POSITIVE affect on the circuit that is off (due to an antagonist)? (Hint: place in order from greatest to lowest positive effect:

Back 33

Greatest to lowest positive affect: Agonist > partial agonist > inverse (no positive effect)

Front 34

Define Efficacy and Potency

Back 34

Efficacy: the extent of the biological response to a drug (a infinite concentration)… Potency: the amount of drug needed to produce a biological effect (where more potent drugs require less concentration to have an effect - albeit not necessarily a maximal effect)

Front 35

On a drug response curve how is a) greater potency demontrated… b) greater efficacy demonstrated?

Back 35

a) more potent the curve is to the left… b) greater efficacy goes higher in reponse

Front 36

On a curve that shows 3 drugs, one has NO cooperativity and the other two have either positive cooperativity and negative cooperativity, how is demontrated?

Back 36

Postive cooperativity has a steeper curve… where negative cooperativity is a shallower curve… both relative to the "no cooperativity" curve

Front 37

Do cooperative curves show Michaelis Menton?

Back 37

no

Front 38

Define desensitization, homo desensitization, and hetero desensitization.

Back 38

Desensitization: decreased response to an agonist over a short period of time… Homologous D: only the stimulated receptor is desensitized… Heterologous D: other receptors are alos desensitized even though they are not stimulated by the initial agonist.

Front 39

what does a quantal dose effect curve show?

Back 39

response is reduced to "plus" or "minus", and a fraction of individuals who respond is plotted vs dose

Front 40

What is the usefulness of quantal dose curves?

Back 40

They are useful in determining therapeutic indices.

Front 41

what are three potential mechanisms for therapeutic vs toxic effects?

Back 41

(1) one DR interaction--> one effector, which can have a therapeutic or toxic toxic effect… (2) one DR interaction --> two effectors: on effector has a therapeutic effect the other receptor has a toxic effect… (3) D+R1 and D+R2 --> each effects a different effector, one effector has a therapeutic effect and the other effector has a toxic effect

Front 42

Give the equation for the therapeutic Index

Back 42

therapeutic index = TD50/ED50… where TD50 is the dose at which a toxic effect is seen in 50% of individuals… ED50 is the dose at which a efficacy is seen in 50% of indivduals

Hint 42

None