Introduction to Drug Action

Yet another pharmacology post! I've decided that I really don't get the order in which these lectures have been in... but oh well.

Be able to answer the question “What is a receptor?”

A receptor is basically something that a drug or another signalling molecule can bind to. When it is bound (or, in some cases, when it isn't bound), it induces some kind of effect. See my earlier post on Biochemical Messengers for more information.

Be able to explain concepts such as agonism, partial agonism and antagonism in terms of drug affinity and efficacy

Firstly I'll explain what "affinity" and "efficacy" mean. "Affinity" refers to a drug's ability to bind to a target. "Efficacy" refers to the degree of receptor activation- a high efficacy means a high activation of receptors.

An "agonist" is a drug that binds to a receptor to induce an effect. Agonists have affinity and efficacy. An antagonist is the opposite: it also binds to a receptor, but it does not cause an effect: instead, it blocks other agonists from having a potential effect. (Rude.) They have affinity, as they do bind to the receptors, but they have no efficacy. A partial agonist is somewhere in between: it causes some effect, but not as much as a full agonist. They also have affinity, but low efficacy.

Be able to explain what is meant by drug selectivity

Drug selectivity, as the term suggests, refers to a drug binding to certain targets but not to others. This is often to do with the structure of the drug. See my previous post on structure-activity relationships for more details.

Be able to describe the relationship between agonist concentration and receptor occupancy or response

Generally, as the concentration of an agonist increases, the number of receptors that are occupied by said agonist also increases. Because of this, the response also increases. The concentration at which half the maximal response is achieved is known as EC50. If a drug has a low EC50, it is said to be more potent; if a drug has a high EC50, it is not as potent. Potency depends largely on affinity and efficacy.

Be able to explain the differences between reversible and irreversible receptor antagonism

Antagonists come in two main types: those that bind temporarily and dissociate (known as "reversible antagonists") and those that get stuck there forever (also known as "irreversible antagonists").

When a reversible antagonist binds, the concentration-effect curve is "shifted" to the right. This means that EC50 is higher, which in turn means that more agonist is required in order to "compete successfully" for receptors. The size of this "curve shift" depends on several factors such as the affinity and concentration of the antagonist.

When an irreversible antagonist binds, there are fewer spaces in which an agonist can occupy. The overall effect is just like having fewer receptors: the maximum effect is decreased, and the slope of the curve is also reduced. Once again, this "curve shift" depends on factors such as concentration.