General Principles Of Pharmacology

Question 1

List the four different kind of ‘drug targets’

Answer 1

Receptor
Enzymes
Carrier / Transporter
Ion channels

*These are all proteins

Question 2

Define Agonist

Give an example

Answer 2

A drug that binds to the receptor and mimics the natural chemical signal.
It will produce the same or enhanced effect as the natural signal

Example: insulin

Question 3

Define Antagonist

Give an example

Answer 3

A drug that binds to a receptor and blocks the natural chemical signal. This will prevent the effect of the natural chemical signal.

Example:

Question 4

Define affinity

Answer 4

The likelihood of the drug binding to a receptor (to bind).

The higher the affinity of the drug for the receptor, the more likely it is to bind to that receptor.

Question 5

Define efficacy

Answer 5

The likelihood the bound drug will elicit a response (activation)

Question 6

Define potency

Answer 6

The combination of affinity and efficacy

Question 7

What is the difference between a full and partial agonist

Answer 7

Full agonist: elicit the maximal tissue response
Partial agonist: may have similar affinity, have less efficacy and less potent (compared to full agonists)

Question 8

Describe the effect effect of competitive antagonists & the effect on the dose response curve of a full agonist

Answer 8

Effect: blocks the receptor, competes with the natural agonist chemical for receptor binding. Surmountable (it can be overcome). Increasing the concentration of the agonist
enough will eventually overcome the action of the competitive antagonist and restore the
tissue response

Curve: A rightward shift -> need more agonist to get the same effect.

Question 9

Describe the effect of irreversible antagonists & the effect on the dose response curve of a full agonist

Answer 9

Effect: only dissociates from the receptor very slowly (or not at all). Non-surmountable. Will have long-lasting effects

Curve: Downward shift -> maximum not achieved, even with increasing agonist dose

Question 10

Explain the nature with an example the form of antagonism: non-competitive

Answer 10

The antagonist will not interact at the receptor (so the agonist binds as normal). The antagonist can block at any point downstream from the agonist binding site (so does not affect the site of binding).

Example: ketamine: enters the ion channel of the NMDA receptor and blocks it.

Question 11

Explain the nature with an example the form of antagonism: chemical

Answer 11

The antagonist combines with a drug in a solution (e.g. GI fluid or plasma) so the effect of the drug is lost. Forms an insoluble and inactive complex.

Example: Protamine neutralises the action of heparin as an antidote to over anticoagulation of heparin.

Question 12

Explain the nature with an example the form of antagonism: physiological

Answer 12

The antagonist has the opposing biological action of the agonist (so it cancels its action out). Often seen in polypharmacy.

Example: Histamine acts on gut mucosa to stimulate acris secretion while omeprazole blocks this effect by inhibiting the proton pump.

Question 13

Explain the nature with an example the form of antagonism: pharmacokinetic

Answer 13

The antagonist reduces the concentration of another drug by altering how the other drug is passed through the body through various pharmacokinetic effects (e.g. decreasing absorption, increasing metabolism or increasing excretion).

Example: Rifampicin speeds up metabolism of many other drugs, reducing their activity.

Question 14

Explain the concept of the therapeutic index

Answer 14

A simple measure of benefit versus risk:

The median toxic dose of a drug (the dose which produces unwanted effects in 50% of the population) divided by the median effective dose (the dose which produces a therapeutic effect in 50% of people).

Question 15

What is Pharmacodynamics

Answer 15

What the drug does to the body
(What does it bind too? What does it target in the body to target a change?)

Question 16

What is pharmacokinetics

Answer 16

What the body does to the drug
(So once administered, how does the drug move through the body, what does the body do to the drug - does it metabolise it, how does it excrete it from the body?)

Question 17

What is a drug?

Answer 17

A ‘drug’ is a chemical that affects physiological function.
A ‘drug’ is any biological active compound taken with the intent of producing a change in the body.

Question 18

What is a drug target

Answer 18

The ‘target’ to which a drug binds in the body.

Question 19

What exception to the rule of drug targets that do not target proteins?

Answer 19

Anti-tumour drugs bind directly to DNA

(e.g. in rheumatology or cancer chemotherapy)

Question 20

An agonist has affinity but no efficacy True or False

Answer 20

False

Question 21

Antagonists are less potent than agonists

Answer 21

True

Question 22

Salbutamol is an agonist True or False

Answer 22

True

Question 23

Competitive antagonists use which sort of chemical bonds hydrogen or covalent

Answer 23

Hydrogen

Question 24

Agonists and antagonists can have similar affinity? True/False

Answer 24

True

Question 25

An irreversible antagonist cannot be reversed with additional agonist? True/False

Answer 25

True

Question 26

Partial agonists can block the activity of a full agonist? True/False

Answer 26

True

Question 27

A drug with narrow therapeutic range is likely to have plasma levels monitored regularly? True/False

Answer 27

True

Question 28

What is a carrier/transport target

Answer 28

Ions and a number of other small molecules such as neurotransmitters are too polar to readily cross cell membranes and so use carrier proteins to move them across membranes. These drugs can inhibit or facilitate the transport of molecules that use carriers.

Question 29

What is an ion target?

Answer 29

Ion channels are proteins which act as ‘gated tunnels’ to allow the passage of ions across membranes. These proteins can be targeted by drugs to block the ion channel, preventing the passage of ions across the membrane as is the case with local anaesthetics. Alternatively, drugs can bind to a different area on the ion channel and modulate its activity, either by promoting channel opening, ‘keeping the gate open’ (e.g. benzodiazepines), or by reducing channel opening, ‘shutting the gate’ (e.g. dihydropyridines).

Question 30

What is an enzyme target?

Answer 30

An enzyme is a protein which speeds up a biological reaction without being chemically altered itself. Drugs which target enzymes inhibit their activity through either:
Competitive (Reversible) inhibition: The drug interacts with the active site of the enzyme in a similar way to the natural substrate binding to the enzyme.
or
Irreversible inhibition: the drug binds to the enzyme using strong covalent bonds which are not easily broken.