L4 - Drug action at receptors

Question 1

Receptors: Two functions:

Answer 1

Are protein macromolecules and usually inserted across lipid bilayer of cell. Protects intracellular content.

Two functions:

1. Recognition/detection
2. Transduction - recognise chemicals and pass info across cell membrane to trigger a response inside cell. Interact with/bind specific chemicals e.g. hormones or NT.

Classified with respect to drug they bind to e.g. ACh receptors. Pharmacologists use specificity of drug and receptor to create drugs that only bind to certain receptors - leads to fewer side effects.

Question 2

Binding of drug (D) and receptor (R)

Answer 2

Binding usually reversible. More drug more receptors occupied. Drug that form covalent bond with receptor are irreversible - can be effective and dangerous e.g. snake venom.

Question 3

Affinity (K_D):

Answer 3

It is the molar conc of the drug required to occupy 50% of receptors at equilibrium.

HIgh affinity = low K_D

Depends on how likely DR is to dissociate to D + R (K_-1).

K₊₁ is the likelihood of D + R binding to form DR.

Whether drug binds to receptor or not depends on random collisions. Have slow dissociation rate when bind to receptor. Length of drug is attached to receptor represents affinity. Only those with affinity bind to receptor.

Question 4

Agonists and Efficacy:

Two types:

Answer 4

Have efficacy so bind to receptor and activate it. Not many drugs activate receptor. Produce a confirmational change in receptor and leads to response.

Naturally occurring NT and hormones are agonists e.g. adrenaline.

Two types:

Full agonists - have high efficacy so are very effective at producing response. Produce max response whilst occupying some receptors.

Partial agonists - have low efficacy so less effective. Don’t produce full response but occupy all receptors.

A drug can change from full to partial agonist if someone creates a new drug with a better response.

Question 5

Antagonist:

Forms of antagonism:

Answer 5

Many clinically useful drugs are antagonist - produce negative effects.

Act to inhibit the effects of NT, hormone and sometimes other drugs.

Froms of antagonism:

1. Chemical - use one drug to chemically inactivate another
2. Pharmocokinetic - one drug alters way body deals with another drug.
3. Physiological - two drugs act to produce opposing effects so cancel each other out. Drugs can be agonists but act on completely different receptors.

Question 6

Competitive and non-competitive antagonists:

Answer 6

Competitive - compete with agonist for same site on receptor. But don’t activate it. Zero efficacy. Block receptor and stop agonist producing a response. Can be reversible or irreversible.

Non-competitive - act on different site on receptor or another molecule closely associated with it. Can be reversible or irreversible.

Reversible competitive antagonistic effects can be overcome by increased conc of agonists. Causes a parallel shift to the right og Log [agonist] vs response. Response is same even if you increase antagonist conc as you would increase agonist conc as well.

Irreversible competitive antagonist cause a shift which is not parallel. Only a few receptors which can work. response decreases. Agonists can’t overcome antagonist.