Nursing Pharmacology Chapter 1: General Principles: Overview and Introduction
Chemical aspects of drugs
The shape of the drug is an important factor in defining the nature of the drug-receptor interaction.
The three-dimensional shape of the drug is thought to interact with a complementary structural binding region of the receptor, typically a protein.
The specific nature of the interaction defines whether the drug acts as an agonist promoting a change in cellular function or as an antagonist which blocks the receptor usually resulting in no direct biological effect.
For example, let's consider acetylcholine or a synthetic analogue bethanechol (Urecholine).
Interaction of these molecules with receptor (nicotinic or muscarinic cholinergic receptor) causes a physiological response -- a decrease in heartbreak for instance.
By contrast, a muscarinic antagonist such as atropine may bind even more tightly than acetylcholine to muscarinic receptor but causes no direct effect.
However, following administration of antagonist a biological response may be observed as a result of receptor blockade.
A clinical example would be bradycardia following acute myocardial infarction.
Bradycardia in this context might be due to excessive parasympathetic (cholinergic) tone and might cause unacceptably low cardiac output or predispose to more serious arrhythmias.
Administration of atropine, by blocking the muscarinic receptor blunts the action of acetylcholine and accordingly may reverse bradycardia.
Acetylcholine, a neurotransmitter, is composed of an "acetyl" group and choline. The linkage between these two group is the target of an enzyme which breaks down the transmitter and terminates its action. This linkage is an "ester" bond.
So, this ester bond is susceptible to hydrolysis, i.e. breakage which may be catalyzed by esterases (acetylcholinesterase is an example).
Some short-acting pharmacological agents are in fact short-acting because they are rapidly hydrolyzed at an ester linkage.
Ester-type local anesthetics
The image below illustrates the relationship between the very small molecule, acetylcholine, and its specific interaction within the very large molecule, acetylcholinesterase.