Module 8

Question 1

What are the two receptor theories that we can use to describe drug receptor interactions?

Answer 1

1) The simple occupancy theory
2) The modified occupancy theory

Question 2

Explain the simple occupancy theory

Answer 2

1) The intensity of a drug’s response is proportional to the number of receptors occupied.
2) The maximal response occurs when all the receptors are occupied.

Question 3

Explain the modified occupancy theory

Answer 3

1) The intensity of a drug’s response is proportional to the number of receptors occupied.
2) Two drugs occupying the same receptor can have different binding strengths (i.e. affinity).
3) Two drugs occupying the same receptor can have different abilities to activate the receptor (i.e. intrinsic activity).

In summary, in addition to accounting for the number of receptors occupied, the modified occupancy theory takes into account the affinity of the drug for the receptor and the ability of the drug to activate the receptor.

Question 4

Define affinity

Answer 4

A measure of how avidly a drug binds to a receptor.

Question 5

Define intrinsic activity

Answer 5

A measure of the ability of a drug once bound to the receptor to generate an effect/activate the receptor.

Question 6

If a drug has a high affinity, it also has high what?

Answer 6

potency

high affinity/high potency

Question 7

If a drug has a high intrinsic activity, it also has a high what?

Answer 7

efficacy

high intrinsic activity/high efficacy

Question 8

Drugs with low intrinsic activity only minimally activate what?

Answer 8

the receptor

Question 9

Define agonist

Answer 9

Agonist –a molecule that binds to a receptor and activates

Question 10

Define antagonist

Answer 10

Antagonists – molecules that bind to a receptor but do not activate it.

Question 11

Define partial agonist

Answer 11

Partial Agonists – molecules that bind to the receptor but have minimal ability to activate it.

Question 12

Are endogenous molecules considered agonists?

Answer 12

Yes

• Since agonists are molecules that activate receptors, endogenous molecules that activate receptors are considered agonists. Some of these include neurotransmitters and hormones.
• Drugs that we design as agonists are often targeted to mimic the action of the body’s endogenous molecules.

Question 13

What can be thought of as having both affinity and intrinsic activity since they are able to bind and activate the receptor?

Answer 13

agonists

Question 14

Dopamine is able to what?

Answer 14

Increase urinary output, increase cardiac output, and decrease urinary output depending on the dose given.

Question 15

What are examples of antagonist drugs?

Answer 15

beta blockers
Antihistamines
gastric acid reducers
opioid receptors

Question 16

What are the three types of antagonists?

Answer 16

1) Competitive Antagonists – Binding occurs at the same site as the agonist and is reversible.
2) Irreversible Antagonists – Binding occurs at the same site as the agonist but is irreversible.
3) Allosteric Antagonists – Binding occurs at a different site than the agonist.

Question 17

When administering a competitive agonist, the dose response curve shifts which way?

Answer 17

To the right

Question 18

Describe competitive antagonists

Answer 18

• Compete for binding with an agonist at the same binding site.
• Binding is reversible.
• If the antagonist and agonist have equal affinity, the one with the highest concentration will occupy the binding site.
• Because the binding is reversible, the effect of a competitive antagonist can be overcome by increasing the concentration of the agonist.

Question 19

On the dose response curve when an irreversible antagonist is administered, the curve shifts in which direction?

Answer 19

Down (affecting the maximal efficacy)

Question 20

Is binding reversible or irreversible for an irreversible antagonist?

Answer 20

binding is irreversible and therefore non-competitive.

Question 21

Describe allosteric antagonists

Answer 21

• Allosteric antagonists bind to a different site on the receptor than the agonist does.
• Binding of the allosteric antagonist changes the conformation of the receptor so the agonist is no longer able to bind.
• The binding of an allosteric antagonist is reversible but not competitive.
• The binding is non-competitive because the agonist and allosteric inhibitor bind to different sites on the receptor.
• Similar to irreversible antagonists, the effects of allosteric antagonists cannot be overcome by increasing the dose of agonist.
• Allosteric antagonists effectively decrease the maximal response that the agonist may elicit.

Question 22

Which direction does a dose response curve shift when an allosteric antagonist is administered?

Answer 22

Down (affecting maximal efficacy)

Question 23

Describe partial agonists

Answer 23

• Partial agonists are agonists that have only minimal or moderate intrinsic activity.
• The maximal efficacy that a partial agonist can produce is less than that of a full agonist.
• Partial agonists are also able to act as antagonists. How is this possible? Remember that a partial agonist has only minimal or moderate activity to activate a receptor. Therefore binding of a partial agonist will cause minimal or moderate activation of the receptor but will also block the binding of a full agonist.

Question 24

Continual exposure to agonists may lead to drug tolerance. What are the three types of drug tolerance?

Answer 24

1) Desensitization – Continuous exposure to an agonist can cause receptor desensitization. In receptor desensitization, the receptor is internalized into the cell or destroyed. The net effect is a decrease in cell surface receptor expression and decreased drug effects.
2) Metabolic Tolerance – Continuous exposure to some drugs results in the induction of drug metabolizing enzymes. Induction of drug metabolizing enzymes may cause a decrease in the plasma concentration of the drug. (remember Module 4?)
3) Tachyphylaxis – A rapid decrease in the response to a drug. Some drugs require a drug free period between administrations to prevent rapidly developing tolerance.

Question 25

Describe receptor upregulation

Answer 25

• Continuous exposure to an antagonist has the opposite effect of tolerance.
• In this case the cell is said to become hypersensitive or supersensitive.
• This occurs because the cell synthesizes more receptors.
• Therefore there are a greater number of receptors at the cell surface and the response increases.