4.1: Principles of Drug Action
Drugs are chemical substances that modify biological responses by interacting with macromolecular targets such as receptors, ion channels, transporters, and enzymes. Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body.
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn activates the target. Some targets respond directly to drugs by opening or closing ion channels. Others initiate a series of molecular events by coupling with downstream effectors to bring about a response.
Unlike agonists, antagonists bind to the target to inactivate them and inhibit the cellular response. Antagonists act by blocking the binding of agonists or endogenous ligands, suppressing target activity. Drugs compete with the endogenous ligand for the ligand binding site on the target. However, some drugs bind to alternative target sites called allosteric sites and act by either enhancing the binding of agonists to the target or blocking it. These drugs are also called allosteric activators and inhibitors.
The physical and chemical properties of drugs often influence their activity. For example, antacids usually contain salts of calcium, magnesium, and aluminum as active ingredients. Such alkaline compounds help neutralize gastric HCl, reducing the acid's corrosive effects on the lining of the esophagus and providing relief from acid reflux and heartburn.
Additionally, several recently approved biologics, such as genetically engineered enzymes, monoclonal antibodies, and genetically modified viruses and microbes, have been approved for therapeutic uses. An example of this is how a genetically modified live oncolytic herpes virus strain can be used to treat melanoma tumors left post-surgery.
Regardless of their mechanism of action, a drug needs to bind specifically to its target molecules to be a useful therapeutic tool. However, the drugs are only somewhat specific. As the concentration of the drug dose increases, the drug can bind to targets other than its actual target, causing various side effects such as inflammation or necrosis in epithelial and connective tissues. It is essential to focus on enhancing drug potency such that the drug is effective at a lower dose and has minimal side effects on the body.
