Lecture 3: How do Drugs Work?

Question 1

What does the extent of antagonism depend on?

Answer 1

The relative amounts of agonist and antagonist

Question 2

What is an allosteric change?

Answer 2

When a non-competitive antagonist binds elsewhere on the receptor, changing its shape/activity so that the agonist can’t bind at the active site

Question 3

How does a non-competitive antagonist affect an agonist?

Answer 3

It reduces the potency and efficacy by irreversibly blocking a fraction of the receptor population

Agonist will then have less efficacy as its ability to produce a maximum response is reduced.

Question 4

What are spare receptors?

Answer 4

Many agonists can produce maximal responses even by activating only a proportion of receptors.

They are still full agonists but remaining receptors are spare

Question 5

What is a partial agonist?

Answer 5

Cannot produce a maximal response even when occupying 100% of the receptors.

They have a LOW efficacy (intrinsic activity)

Question 6

Can an agonist be an antagonist? Give an example

Answer 6

On its own a partial agonist acts as a weak agonist

But in the presence of an additional full agonist, a partial will act as a weak antagonist

e.g. Pindolol prevents HR falling too low (partial agonism) and during exercise it prevents HR rising too high when adrenaline is being produced (partial antagonism)

Question 7

What drug targets are there?

Answer 7

1. Ligand gated ion channels (LGIC)
2. G-protein coupled receptors (GPCRs)
3. Kinase-linked receptors
4. Nuclear receptors
5. Voltage-gates ion channels (VGIC)
6. Enzymes
7. Transporters

Question 8

How may drugs act at ion channels?

Answer 8

Either agonists or antagonists (channel blockers)

e.g. local anaesthetic blocking sodium channels

Question 9

How may drugs act at an enzyme active site?

Answer 9

• As an inducer
• As an inhibitor (more common)
• Pro-drug or false substrate

e.g. Inhibitor: aspirin inhibiting cyclooxygenase (COX)
e.g. False sub: anticancer drugs (methotrexate)

Question 10

How may drugs act at transporters?

Answer 10

• Allosteric
• Bind to carrier site preventing substrate from being carried
• False substrate

e.g. SSRIs (fluoxetine)

Question 11

How do membrane transport molecules work

Answer 11

Allow molecules to pass through an impermeable membrane.

1. Passive transport down conc gradient
2. Facilitated transport (only occurs in exchange for another molecule)
3. Active transport where energy is required (ATP) pumped against concentration gradient