1.6 Pharmacodynamics

Match receptor classification with duration of response.

• Ligand-gated ion channels

• Enzyme-linked receptors

• G protein–coupled receptors

• Intracellular receptors

• Response is very rapid and short (milliseconds)

• Duration of response is minutes to hours

• Duration of response is seconds to minutes

• Duration of response is weeks to months

• Ligand-gated ion channels → Response is very rapid and short (milliseconds)

• Enzyme-linked receptors → Duration of response is minutes to hours

• G protein–coupled receptors → Duration of response is seconds to minutes

• Intracellular receptors → Duration of response is weeks to months

Upon binding to α-adrenoceptors on the membranes of vascular smooth muscle, phenylephrine mobilizes intracellular Ca²⁺, causing contraction of actin and myosin filaments. The shortening of muscle cells decreases arteriole diameter, increasing resistance to blood flow and raising blood pressure. All effects resemble the endogenous ligand norepinephrine.

What kind of ligand is phenylephrine?

Answer choices:

a. Inverse agonist

b. Full agonist

c. Partial agonist

d. Competitive antagonist

e. Non-competitive antagonist

f. Antagonist

g. Allosteric modulator

b. Full agonist

Pindolol increases heart rate by activating β-adrenergic receptors in the absence of epinephrine and other β-adrenergic agonists. However, it decreases heart rate in the presence of epinephrine.

What kind of ligand is pindolol?

Answer choices:

• Non-competitive antagonist

• Inverse agonist

• Allosteric modulator

• Full agonist

• Competitive antagonist

• Partial agonist

• Antagonist

• Partial agonist

Epinephrine increases the force of cardiac contractions by activating β-adrenergic receptors. It may cause the same response even when some β-adrenergic receptors are occupied by their antagonist propranolol.

What is the role of “spare” β-adrenergic receptors in this event?

Answer choices:

• Spare receptors are intracellular and may differentiate into other receptor families

• Spare receptors are present if not all receptors are required for full effect

• Only adrenergic receptors may be spare

• Spare receptors differ from others in chemical structure

• Spare receptors are present if not all receptors are required for full effect

Histamine acts on histamine receptors and causes bronchial spasm. β-adrenergic agonist albuterol causes bronchial dilation and relieves bronchial spasm.

What kind of interaction occurs between histamine and albuterol?

Answer choices:

• Physiological antagonism

• Pharmacological antagonism

• Physical/chemical antagonism

• Pharmacological agonism

• Physiological agonism

• Allosteric modulation

• Physiological antagonism

Heparin acts on antithrombin III and inhibits the coagulation cascade. Protamine sulfate does not act on antithrombin III but binds heparin and inactivates it.

What kind of interaction occurs between heparin and protamine sulfate?

Answer choices:

• Pharmacological antagonism

• Physical or chemical antagonism

• Pharmacological agonism

• Physiological antagonism

• Physiological agonism

• Allosteric modulation

• Physical or chemical antagonism

What receptors have only hydrophobic ligands?

Answer choices:

• Spare receptors

• Ligand-gated ion channels

• Enzyme-linked receptors

• Intracellular receptors

• G protein–coupled receptors

• Intracellular receptors

Insulin acts at the extracellular domain of a membrane-spanning tyrosine kinase and causes its phosphorylation. The kinase then activates intracellular enzymes responsible for glucose catabolism.

To which family of receptors does tyrosine kinase belong?

Answer choices:

• Ligand-gated ion channels

• Enzyme-linked receptors

• Spare receptors

• Intracellular receptors

• G protein–coupled receptors

• Enzyme-linked receptors

Question:

What ligands do not bind to the agonist receptor site, but instead bind to another region of the receptor and change the response to an agonist?

Answer choices:

a. Inverse agonists

b. Allosteric modulators

c. Full agonists

d. Antagonists

e. Partial agonists

f. Competitive antagonists

g. Non-competitive antagonists

b. Allosteric modulators

What antagonists decrease the potency of an agonist but have no effect on its efficacy even in the absence of “spare” receptors?

Answer choices:

• Full agonists

• Non-competitive antagonists

• Allosteric modulators

• Partial agonists

• Competitive antagonists

• Antagonists

• Inverse agonists

• Competitive antagonists

What pharmacological antagonists form irreversible covalent bonds at the agonist receptor site?

Answer choices:

• Non-competitive antagonists

• Full agonists

• Competitive antagonists

• Antagonists

• Allosteric modulators

• Inverse agonists

• Partial agonists

• Non-competitive antagonists

A 55-year-old patient took diazepam daily for anxiety. Initially, 5 mg was effective. After several weeks, the same dose was ineffective. Increasing the dose to 10 mg produced the same relief as initially.

What phenomenon occurred, and what happened to potency and efficacy?

Answer choices:

• Efficacy of diazepam decreased

• Potency of diazepam decreased

• Potency of diazepam increased

• Efficacy of diazepam did not change

• Withdrawal

• Efficacy of diazepam increased

• Tolerance

• Potency did not change

• Potency of diazepam decreased

• Efficacy of diazepam did not change

• Tolerance

Select the true statements.

Answer choices:

• If 10 mg of drug A produces the same response as 100 mg of drug B, drug A has higher potency than drug B

• Variation in response is most likely with a large therapeutic index

• Potency is usually more important than efficacy

• If 10 mg of drug A produces the same response as 100 mg of drug B, drug A has higher efficacy

• A competitive antagonist increases the ED50

• Higher efficacy always means higher potency

• Drug A has higher clinical efficacy than drug B

• If 10 mg of drug A produces the same response as 100 mg of drug B, drug A has higher potency than drug B

• A competitive antagonist increases the ED50

Binding of an agonist causes receptor endocytosis and sequestration, preventing further agonist interaction.

What phenomenon is described, and what happens to efficacy if there are no spare receptors?

Answer choices:

• Efficacy of agonists decreases

• Efficacy is not affected

• Tachyphylaxis

• Pharmacodynamic tolerance

• Pharmacokinetic tolerance

• Efficacy increases

• Down-regulation of receptors

• Efficacy of agonists decreases

• Pharmacodynamic tolerance

• Down-regulation of receptors

What is the meaning of the letter “s” in G protein–coupled receptors (Gs)?

Answer choices:

• Activation of phospholipase

• Inhibition of phospholipase

• Activation of cyclases

• Inhibition of body functions

• Inhibition of cyclases

• Activation of cyclases

What is the correct sequence of events following binding of epinephrine to Gs protein–coupled receptors?

Answer choices (correct order):

• Activation of protein kinase

• Dissociation of G protein

• Replacement of GDP by GTP at α-subunit

• Increase in cAMP synthesis

• Activation of the receptor following ligand binding

• Formation of α-GTP and βγ subunits

• Stimulation of adenylyl cyclase

• Activation of the receptor following ligand binding

• Replacement of GDP by GTP at α-subunit

• Dissociation of G protein

• Formation of α-GTP and βγ subunits

• Stimulation of adenylyl cyclase

• Increase in cAMP synthesis

• Activation of protein kinase