Pharmacodynamics

Question 1

What is the definition of pharmacology?

Answer 1

The study of how chemical agents (drugs) influence the function of living systems

Question 2

What does pharmacodynamics look at and how does it do this?

Answer 2

Looks at what the drug does to the body. Where is the effect produced? What is the target? What is the response after interaction with the target?

Question 3

What is a drug target and what are the main 4 categories?

Answer 3

A drug target is something the drug must bind to to produce a measurable effect in the body (usually a protein).
The 4 main categories are:
Receptors (molecules whos function it is to recognise and respond to endogenous chemical signals), enzymes, ion channels, and carrier proteins.

Question 4

What is specificity and how does it influence drug effects on the body?

Answer 4

Specificity is the ability of drugs to only bind to targets of a certain type, and this determines the effect. Dopamine, serotonin, noradrenaline have similar shapes so some specificity to eachother’s targets, leading to “side effects”.
Effective therapeutic agents must have a high degree of specificity.

Question 5

What is a drug?

Answer 5

A chemical substance of known structure, that produces a biological effect in a living organism. (Apart from a nutrient or dietary ingredient)

Question 6

In which ways can a drug act on a target?

Answer 6

Enhance activation of a target (stimulate an effect) or prevent activation of a target (blocking an effect).

Question 7

How does increasing the dosage of a drug change the drug effect?

Answer 7

The specificity will reduce due to the increased concentration of the drug and other targets may be activated or blocked, leading to side effects. Peroglide at 0-5nm has an anti parkinsons effect, but at >5nm it interacts with serotonin receptors causing hallucinations.

Question 8

What is the therapaeutic window and the therapeutic index?

Answer 8

The therapeutic window is the difference between the drug dose that causes therapeutic effects and the drug dose that causes toxic effects. The therapeutic index is the value for the therapeutic window which makes it easier to compare different drugs.

Question 9

How are therapeutic and toxic effects measured?

Answer 9

Therapeutic effects are measured by ED50 - the effective dose required to produce a specific effect in 50% of the population.
Toxic effects are measured by TD50 - the effective dose required to produce a specific toxic effect in 50% of the population.

Question 10

How is the Therapeutic Index calculated? What does the number tell us?

Answer 10

TD50/ED50. A higher therapeutic index tells us that the drug is safer. A higher dose is required to produce a toxic effect than to produce a therapeutic one.

Question 11

What is drug-receptor interaction?

Answer 11

Drug + Receptor —> Drug-Receptor Complex. This reaction is reversible.

Question 12

What is affinity?

Answer 12

The factor that determines the binding strength of the drug to the target. A higher affinity also leads to higher
and longer receptor occupancy. Each-drug receptor interaction lasts milliseconds but a higher affinity –> stronger interaction –> more receptors being occupied at any given time.

Question 13

What is efficacy?

Answer 13

The ability of the drug to produce an effect once it is bound to the target.

Question 14

What is are agonists and antagonists?

Answer 14

Agonist - Activates the target once bound, has an affinity for the target, and also has efficacy (it produces a response). Drugs often exogenous agonists.
Antagonist - Blocks the effects of endogenous agonists by not allowing them to bind to their target. They have affinity for the target but produce no effect of their own (no efficacy).

Question 15

What is the difference between full and partial agonists?

Answer 15

A full agonist is a molecule that is able to stimulate the maximal response from the target. (It has full efficacy)
A partial agonist is not able to produce the maximal response from a target. (They have partial efficacy)

Question 16

How do the log-dose response curves of full and partial agonists differ?

Answer 16

Full agonists reach maximum response, whereas partial agonists never do. So the curve of a partial agonist is to the right and always below the curve of a full agonsit.

Question 17

What is the difference between competitive and irreversible antagonists?

Answer 17

Competitive antagonists block the target only transiently, whereas irreversible antagonists dissociate very slowly/not at all from the target. Competitive antagonism is surmountable (if you add enough drug the antagonist will be out competed) but irreversible antagonism is not surmountable.

Question 18

How do the log-dose response curves for drugs with competitive and irreversible antagonists differ?

Answer 18

Drug and competitive antagonist - The graph with antagonist is just shifted to the right, no decrease in maximal response.
Drug and irreversible antagonist - The graph with irreversible antagonist has maximal output lower than drug alone.

Question 19

What is potency?

Answer 19

Potency is the measure of the strength of the drug. The more drug is required to produce a specific effect, the less potent it is.

Question 20

How is potency measured?

Answer 20

Potency is measured by ED50 (arbitrary) but is helpful to compare different drugs.

Question 21

What is the difference between potency and efficacy?

Answer 21

A highly potent drug produces a large response at low dose.

A highly efficacious drug produces (close to) maximal response, but this response is not related to dose.

Question 22

Which property is more important for clinical applications? Potency or efficacy?

Answer 22

Efficacy because if the drug is less potent we just give a higher dose. If the drug is extremely potent but not very efficacious then we will never get the maximal response we are looking for.