Pharmacodynamics 1 and 2

These lecture had summary slides, not "learning outcomes" slides, but the first lecture had "key concepts" on the title slide so that's what I'll be basing this post on :)

Affinity & efficacy

Affinity is the ability of a drug to bind to its target. Affinity is determined by how well the shape of the drug fits the binding site, and how strong the bonds are between drug and binding site. The higher the affinity, the more readily the drug binds, and the less drug you need to have an effect. The K_A is the concentration of drug at which 50% of receptors are bound. The lower the K_A, the higher the affinity. Sometimes a drug might have a higher affinity (lower K_A) for one receptor than for another- for instance, adrenaline has a higher affinity for beta-receptors than for alpha-receptors.

Efficacy is the ability of a drug to have an effect once bound. The higher the efficacy, the greater the effect.

Agonism & antagonism

Agonists are drugs that have an effect by binding to the target. As such, agonists have both affinity and efficacy. A full agonist has high efficacy, while a partial agonist has lower efficacy. An example of an agonist is salbutamol (Ventolin), which binds to and activates beta-2 adrenoceptors.

Antagonists are drugs that have an effect by blocking a target. As such, antagonists have affinity, but no efficacy. An example of an antagonist is metoprolol, which blocks beta-1 adrenoceptors.

Selectivity

Selectivity refers to the ability of a drug to bind to only specific targets. Selectivity occurs because a drug has a higher affinity for one receptors or a set of receptors than for other receptors. It is desirable to have a highly-selective drug, as that means that there will be fewer unwanted effects due to binding at other sites. All drugs lose their selectivity at high doses because a higher concentration of a drug means that there will be more binding to receptors that a drug would otherwise have a low affinity for.

Potency & effectiveness

Potency refers to the concentration of a drug that is needed to have an effect. A less potent drug needs a higher dose to achieve the same effect as a more potent drug. Usually, the potency of a drug is not very important, unless you are administering the drug in such a way that the amount of a drug matters (e.g. transdermal patches).

Effectiveness refers to the maximum effect that a drug can have. A more effective drug has a greater maximum effect than a less effective drug. For example, morphine is better at reducing pain than paracetamol. Effectiveness is much more important than potency in deciding which drug to give a patient.

Dose-response relationship

The dose-response relationship shows the level of effect that you can get for a specific dose of a drug. Generally, the dose-response curve is S-shaped ("sigmoidal")- the drug has little effect at low doses, then as you increase the dose the level of response rapidly increases up to a point before tapering off again.

Adverse effects

Adverse effects are unwanted effects from a drug. Adverse effects usually happen when the dose is too high. This may be due to a loss of selectivity at high doses (off-target side effects), or from an effect that is stronger than you actually need (on-target side effects). For instance, if you have low blood pressure, you might take a drug that increases your blood pressure, but if you take too much of that drug, then you'll end up with high blood pressure, which also isn't good.