Lecture 29

Question 1

With what bond does drug mostly bind to drug receptor? (3)

Answer 1

hydrogen, ionic, or hydrophobic bonds with receptor

*Rarely, drugs form covalent bonds with their receptor

Question 2

Which characteristics of drug determine whether it will bind to a particular receptor or not? (3)

Answer 2

size, shape, and charge of a drug

Question 3

3 examples of drug that target ion channel

Answer 3

local anesthetics (block voltage-gated sodium channel)
Sedative-hypnotics
Anti-epileptics

Question 4

How does drug targeting ion channel work?

Answer 4

drugs act by altering the conductance of ion channels

Question 5

How does local anasthetic work?

Answer 5

the drug permeate through cell membrane and bind to cytosolic side of voltage-gated sodium channel blocking the channel.

Question 6

2 examples of drugs that target g-protein linked receptor

Answer 6

1. albuterol (beta2-agonist)

2. Propranolol (beta-antagonist)

Question 7

2 examples of enzyme-linked receptor

Answer 7

1. insulin receptor

2. epidermal growth factor receptor

Question 8

What happens if gain-of-function mutation occur in tyrosine kinase receptor?

Answer 8

Tyrosine kinase receptors play a role in cellular growth and differentiation, so it is proto-oncogene. If the mutation occur, it can lead to cancer. So inhibitor of receptor is anticancer agents.

Question 9

What is the drug imatinib?

Answer 9

tyrosine kinase inhibitor effective for leukemia

Question 10

3 examples of nuclear receptor

Answer 10

1. steroid hormone
2. thyroid hormone
3. vitaminD

Question 11

Mechanism of nuclear receptor

Answer 11

hormone permeates through cell membrane and binds to intracellular receptor in cytosol. Then, hormone-receptor complex enters nucleus to bind to DNA, which leads to transcription.

Question 12

3 examples of drugs that target enzyme

Answer 12

aspirin, ibuprofen, omeprazole

Most of these drugs work by inhibiting enzyme

Question 13

examples of drugs that target transporter

Answer 13

prozac block serotonin re uptake by bind to transporter at synamptic cleft (used for treating psychiatric disorder)

Question 14

examples of drugs that target structural proteins

Answer 14

some anticancer drugs bind to tubulin and prevent polymerization of spindle fiber, arresting cell division at metaphase.

Question 15

1 examples of drugs that does not bind to receptor

Answer 15

antacids does not interact with receptor, but neutralize gastric acid chemically.

Question 16

2 types of dose-response curves

Answer 16

graded & quantal

Question 17

Equation and shape of graded dose-response curve

Answer 17

E= (Emax *C) / (C+EC50)

Hyperbolic curve

Question 18

B= (Bmax*C) / (C + KD)

What does equation mean?

Answer 18

it is a relation between drug bound (B) to receptors and the concentration (C) of free drug

Question 19

B= (Bmax*C) / (C + KD)

In this equation, what does KD mean?

Answer 19

KD characterize the receptor’s affinity for the drug. Lower the KD, binding affinity is high.

Question 20

Compare binding curve and dose-response curve

Answer 20

shape looks the same (hyperbolic)
but binding curve is the relationship between drug bound to receptors and concentration of free drug while drug-response curve is relationship between concentration of drug and maximal effect of drug.

Question 21

How does logarithm of concentration change the shape of graded-dose-response curve and binding curve?

Answer 21

change from hyperbolic to sigmoidal curve

Question 22

What does it mean if EC50 is lower than KD?

Answer 22

It means an agonist does not have to occupy all receptor to evoke a full response. because certain number of receptors are spare and signal amplification occur. Due to signal amplification, not all receptor has to be bound to induce full effect of drug.

Question 23

Efficacy

Answer 23

magnitude of the response a drug produces.

maximal efficacy = E max

Question 24

Potency

Answer 24

a measure of concentration or amount of drug necessary to produce an effect of a given magnitude, determined by EC50

Question 25

Difference between agonist and antagonist and their effect on efficacy and affinity.

Answer 25

Agonist binds to receptor and brings about an effect, thus have receptor affinity and efficacy. Antagonist inhibits the action of an agonist but has no effect in the absence of agonist. Thus it has receptor affinity but no efficacy.

Question 26

Competitive antagonism can be reversible and irreversible. Compare and contrast in terms of Emax and EC50.

Answer 26

For reversible, Emax is the same, EC50 moves to left. The antagonist is surmountable by adding more agonist For irreversible, Emax is reduced, EC50 same. The antagonist is insurmountable, since receptor can respond to agonist.

Question 27

What is noncompetitive antagonism? (in terms of Emax, EC50)

Answer 27

it is allosteric antagonism, where antagonist binding at different site of agonist reduces action of agonist. * Insurmountable, thus Emax decreased, EC50 decreased

Question 28

The curve shape of irreversible competitive antagonism and noncompetitive antagonism, are the same?

Answer 28

YES

Question 29

Two types of nonreceptor antagonism

Answer 29

physiological and chemical antagonism

Question 30

What is physiological antagonism? & example

Answer 30

One drug opposes another drug but through different receptors ex) epinephrine (increase BP and bronchodilation) & histamine (decrease BP and bronchoconstriction)

Question 31

What is chemical antagonism? & example

Answer 31

a chemical antagonist reacts chemically with an agonist to form an inactive product. ex) protamine, a protein which is positively charged, counteracts the effect of heparin (negatively charged)

Question 32

Difference between full and partial agonist. Their effect on Emax and efficacy

Answer 32

Partial agonist produce submaximal response at full receptor occupancy than agonist >> lower E max >> less efficacy * Partial agonist can act as competitive antagonist in the presence of full agonist, by competing with full agonist for receptor occupancy.

Question 33

What is constitutive activity of receptor?

Answer 33

many receptor system shows some activity in the absence of agonist, that fraction of the receptors is always in the active state

Question 34

What is inverse agonist

Answer 34

it reverse the constitutive activity of the receptor

Question 35

What is quantal dose-effect curves?

Answer 35

it plots the fraction of population that responds to a given dose of drug as a function of drug dose, unlike graded, it defines response as either present or not present.

Question 36

Difference between ED50, TD50, LD50

Answer 36

ED50 : Dose at which 50% individuals exhibit specified quantal effect TD50: Dose at which a particular toxic effect in 50% of animals produced LD50 : Dose required to cause death in 50% of animals

Question 37

Therapeutic index (2)

Answer 37

TD50/ED50 or LD50/ED50

Question 38

Describe safe drug in terms of TD50 and ED50

Answer 38

Safe drug will have large toxic dose and a small effective dose

Question 39

What is therapeutic window?

Answer 39

the dosage range between the minimum effective therapeutic concentration and the minimum toxic concentration