Pharmacodynamics

Question 1

What are the four major receptor families?

Answer 1

Transmembrane ligand-gated ion channels, transmembrane G protein-coupled receptors, enzyme linked receptors, and intracellular receptors.

Question 2

Give an example of a ligand-gated ion channel, and state how long the response might last.

Answer 2

Cholinergic nicotinic receptors; a few milliseconds.

Question 3

Give an example of a transmembrane G protein-coupled receptor, and state how long the response might last.

Answer 3

Alpha and Beta adrenoreceptors; several seconds to minutes.

Question 4

Give an example of an enzyme-linked receptor, and state how long the response might last.

Answer 4

Insulin receptors; minutes to hours.

Question 5

What is one key feature of the most common types of enzyme-linked receptors?

Answer 5

Tyrosine kinase activity; when the ligand binds, it causes conformational changes in the enzyme, leading to autophosphorylation of the tyrosine kinase. The tyrosine kinase is now activated and can now phosphorylate tyrosine residues on other proteins in the cell.

Question 6

Give an example of an intracellular receptor, and state how long the response might last.

Answer 6

Steroid receptors; hours to days.

Question 7

How do intracellular receptor ligands enter the cell?

Answer 7

They diffuse through the cell membrane, meaning they are reasonably lipid-soluble.

Question 8

What are some common targets of intracellular receptor ligands?

Answer 8

Most often, transcription factors; also structural proteins, enzymes, RNA, and ribosomes.

Question 9

Why are cellular responses to intracellular receptor activation not observed until 30 minutes or more have passed?

Answer 9

Since most intracellular receptors are transcription factors, effects aren’t observed until the modified gene expression (and therefore protein synthesis) has had time to occur. This is also why the effect of intracellular receptor activation is significantly longer than other types of receptors.

Question 10

What is the definition of an agonist?

Answer 10

An agent that can bind to a receptor and elicit a biologic response.

Question 11

What is the definition of an antagonist?

Answer 11

A drug that decreases or opposes the actions of another drug or endogenous ligand. The key point here is that an antagonist has no effect is an agonist is not present.

Question 12

What does EC50 represent?

Answer 12

The concentration of a drug producing an effect that is 50% of the maximum.

Question 13

What is efficacy?

Answer 13

The ability of a drug to elicit a response when it interacts with a receptor.

Question 14

What is maximal efficacy, and what condition is necessary to assume it?

Answer 14

Maximum efficacy is when no increase in response is observed if more drug is added. This assumes that all receptors are occupied by the drug.

Question 15

What is potency?

Answer 15

A measure of the amount of drug necessary to produce an effect of a given magnitude.

Question 16

What does Kd represent?

Answer 16

The equilibrium dissociation constant for the drug from the receptor. (The higher the value of Kd, the weaker the interaction of the drug with the receptor.)

Question 17

What is a way to mathematically represent the relationship between drug concentration and bound receptors?

Answer 17

[DR]/[Rt] = [D]/(Kd + [D])
Where [DR] is the concentration of bound drug, [Rt] is the total concentration of receptors, [D] is the concentration of free drug, and Kd is the equilibrium dissociation constant for the drug from the receptor.

Question 18

If we wish to mathematically represent drug concentration and effect, what assumptions must be met?

Answer 18

1: Magnitude of the response is proportional to the amount of receptors bound.
2: Emax occurs when all receptors are bound.
3: Binding of the drug to to the receptor exhibits no cooperativity.

Question 19

What is a way to mathematically represent the relationship between drug concentration and effect?

Answer 19

[E]/[Emax] = [D]/(Kd + [D])
Where [E] is the effect of the drug at concentration [D], [Emax] is the maximal effect of the drug, [D] is the concentration of free drug, and Kd is the equilibrium dissociation constant for the drug from the receptor.

Question 20

What is a full agonist?

Answer 20

A drug that binds to a receptor and produces a maximal biologic response that mimics the response to the endogenous ligand. Full agonists generally have strong affinity for the receptor and good efficacy.

Question 21

What is a partial agonist?

Answer 21

An agonist that cannot reach Emax but does have an efficacy greater than zero. A partial agonist may have a greater affinity for a receptor than a full agonist, meaning that it has potential to act as an antagonist of a full agonist in certain conditions.

Question 22

What is an inverse agonist?

Answer 22

A drug that stabilizes the inactive form of a receptor as opposed to the active form. These drugs exert an opposite pharmacological effect of receptor agonists.

Question 23

What is a competitive antagonist?

Answer 23

A drug which binds to the same site on a receptor as the receptor’s agonist. Competitive antagonists shift the drug response curve to the right, since the effect of the antagonist can be overcome with increasing concentration of agonist. (Emax can still be reached.)

Question 24

What is an irreversible antagonist?

Answer 24

A drug which binds covalently (or with high affinity) either to the same site on a receptor as the receptor’s agonist, or to an allosteric site, thereby decreasing the receptors available to the agonist and decreasing Emax (assuming no spare receptors are present). This effect cannot be overcome by adding more agonist.

Question 25

What is a simple way to remember the difference between competitive antagonists and irreversible antagonists?

Answer 25

Competitive antagonist: decreases agonist potency.

Irreversible antagonist: decreases agonist efficacy.

Question 26

How does functional antagonism work?

Answer 26

A functional antagonist acts at a separate receptor to initiate effects that are functionally opposite to those of the agonist.

Question 27

Give an example of funtional antagonism.

Answer 27

Epinephrine causes bronchodilation by binding β2-adrenoceptors. This counteracts bronchoconstriction caused by histamine binding to H1 histamine receptors.

Question 28

How does chemical antagonism work?

Answer 28

A chemical antagonist prevents the actions of an agonist by modifying or sequestering the agonist so it cannot bind to and activate its receptor.

Question 29

What ratio defines the therapeutic index?

Answer 29

TD50/ED50

dose which produces toxic effect in half of population)/(dose which produces a desired response in half of population

Question 30

What equation represents the relationship between pH and pKa?

Answer 30

pH=pKa + log ((A-)/(HA))

pH=pKa + log ((B)/(BH+))