S1B5 - Pharmacodynamics

Question 1

Describe the effects of a partial agonist in the setting of low endogenous ligand concentrations.

Answer 1

Partial agonists can display both agonistic and antagonistic effects:

• When the amount of endogenous ligand is high → competitive antagonist
• When the amount of endogenous ligand is low → agonist

Question 2

What effect do competitive antagonists have on a particular drugs efficacy?

Answer 2

100% of maximal response can still be attained by adding more agonist (overcome competitive inhibition). The efficacy remains unchanged.

Question 3

You are a physician-scientist in charge of investigating a certain Drug X. During a phase I clinical trial, you find that co-administration of a commonly prescribed Drug Y causes the dose-response curve of Drug X to shift to the right. In this circumstance, what is happening to the potency of Drug X?

Answer 3

The administration of a second agent can affect the potency of a drug or agonist, which appear as horizontal shifts of the dose-response curve:

• Left shift = Increased potency
• Right shift = Decreased potency

Question 4

In the case of spare receptor phenomena, what occurs when a drug only partially occupies the available receptor population?

Answer 4

Emax is often reached at a drug concentration which does NOT occupy 100% of the receptors.

• This is due to a concept known as spare receptors.
• Receptors are referred to as spare when the administration of a drug dose that only causes partial occupation of the receptor population results in a maximal biological or physiological response.

Question 5

How will the addition of a competitive antagonist affect the potency and efficacy of a drug?

Answer 5

Competitive antagonists decreases drug potency, causing the curve to shift to the right

Question 6

What effect does a noncompetitive antagonist have on the potency of a drug?

Answer 6

Noncompetitive antagonists do not affect potency.

• Since noncompetitive antagonists bind to a site separate from the active site for a receptor, any receptor that the antagonist binds to is effectively non-functional.
• This decreases efficacy, or Emax, as previously mentioned. However, this also means that the EC50 decreases to the same extent. As a result, the concentration of agonist at which EC50 is reached does not change.

Question 7

What graphical representations are used to evaluate pharmacodynamics?

Answer 7

Pharmacodynamics describe the effect of the drug on the body, which is typically expressed through dose-response curves.

Question 8

For a given drug or pharmacologic agonist, what does “efficacy” mean? On which axis of the dose-response curve is it found?

Answer 8

Efficacy (Emax) is defined as the maximal response produced by the drug/agonist. On a dose-response curve for a given drug, efficacy is represented by the y axis.

Question 9

When do noncompetitive antagonists behave like competitive antagonists? What other antagonist do noncompetitive antagonists behave like?

Answer 9

At low concentrations noncompetitive antagonists behave like competitive antagonists. Irreversible competitive antagonists also behave similarly to noncompetitive antagonists.

Question 10

How will the addition of a noncompetitive antagonist affect the efficacy of a drug?

Answer 10

Noncompetitive antagonists cannot be overcome with increased agonist substrate concentration, which causes a decrease in efficacy (Emax).

• This means that for a given agonist (i.e. norepinephrine), the co-administration of a noncompetitive antagonist decreases the maximal response possible in the target tissue of interest.
• As a result, the dose-response curve shifts downward.

Question 11

On a dose-response curve, which axis represents the potency of a drug?

Answer 11

Potency (EC₅₀) is represented by the x axis on a dose-response curve. Potency represents the concentration at which a drug or an agonist elicits 50% of its maximal response.

Question 12

How do partial agonists compare with full agonists in terms of efficacy and potency?

Answer 12

Partial Agonist have a lower efficacy at all doses relative to a full agonists. Potency is an independent factor (can have more, less, or equal potency compared to the original agonist).

Question 13

Atropine is injected into a cholinergic nerve terminal within a salivary gland and the dose response curve is measured. Curve AB represents the nerve in the absence of atropine and curve CD represents the nerve terminal in the presence of atropine. The Y axis represents increasing gland secretions. The X-axis represents increasing ACh dosage. Which of the following is an accurate statement?

A) Atropine is a noncompetitive antagonist

B) Potency of ACh is decreased with Atropine present

C) Atropine bindes and activates the ACh receptor

D) Atropine decreases the efficacy point of the dose response curve

E) Atropine does not bind on ACh receptor

Answer 13

Potency of ACh is decreased with Atropine present

Answer Explanation

Atropine is a competitive antagonist that binds on the ACh site but does not activate the receptor in any way. This is shown by the competitive antagonist dose response curve. In the chart shown, the curve from A to B represents acetylcholine dose/response in the absence of atropine. The curve from C to D is in the presence of atropine. In the presence of atropine, ACh shows decreased potency but equal efficacy. As with any competitive antagonist, increasing the substrate (ACh) will ameliorate the antagonist effect of atropine