Key Topics

• • Introduction to therapeutics – pharmacodynamics and the basis for drug action
• • Molecular targets for drug action – receptors, enzymes, ion channels and carrier proteins
• • Selective toxicity – the basis of antibacterial, antiviral and antifungal drug action, and cancer chemotherapy

Learning Objectives

• • Be familiar with the main types of functional protein that serve as the molecular targets for drug action
• • Be aware that in most cases, altering the activity of these proteins alters chemical signaling in the body, and hence control of body function
• • Be familiar with how drugs, such as antibiotics, are able to exert a selectively toxic effect
• • Be aware of the challenges posed in developing antiviral drugs and drugs for the treatment of cancer

Introduction

Therapeutics has its roots in the historical use of herbal remedies and natural potions. However, the modern practice of therapeutics really began in the twentieth century. The herald for this new era was the German physician, Paul Ehrlich. Ehrlich sowed the seeds for transforming therapeutics into a science by insisting that drug action could be explained in terms of chemical and physical reactions. The understanding of how drugs produce their effects represents the area of therapeutics known as pharmacodynamics.

During the twentieth century, the advent of many effective therapeutic agents began to deliver immeasurable benefits to society. Perhaps the biggest single advance in medicine was the development of antibiotic therapies, exemplified by the work of Florey, Chain and Fleming on penicillin. The introduction of these novel treatments transformed what had previously been fatal or life-devastating diseases into manageable conditions.

However, we cannot be complacent. There are still many areas of practice where our current therapies have limited efficacy, or are associated with unwanted, or side, effects. For example, many cancer therapies come with significant side effects. In dental practice you’ll see some of the most severe side effects associated with cancer treatment, such as stomatitis. It will only be through making cancer treatments more specific in the way they target cancerous cells, that we will be able to overcome many of these issues. Another challenge we face is the ability of bacteria to develop resistance to antibiotic therapy. In developed countries, antibiotic-resistant bacteria are now responsible for more deaths than HIV/AIDS. If we do not respond appropriately to these issues, we could return to an era where bacterial infections are no longer treatable. Hence therapeutics is, and needs to be, a constantly evolving science.

In dentistry, therapeutics may not be such a major component of daily practice as compared to general medical practice. However, an understanding of therapeutics is one of the cornerstones of good clinical dental practice. Pain-free dentistry would not be possible without the use of local anaesthetics, while analgesics are used to manage peri- and post-operative pain. In dental practice, the primary approach to managing microbial infection is surgical, however antibiotics do provide an important adjunct therapy, particularly in the case of a spreading infection. Dental practitioners also rely on drugs to manage fungal and viral infections, and inflammation. Other common uses of drugs in the dental clinic are to manage patient anxiety and to provide sedation for patients. However, this is only one side of the coin. Being aware of patients’ general medical conditions, and their associated medications, is central to providing safe and effective treatment. Patients’ medications may impact directly upon their oral health, for example many common medications cause the problem of xerostomia. In addition, medications may impact upon how a dentist manages a patient within the dental clinic. A significant number of patients may be receiving anticoagulant therapy in order to reduce their risk of a thrombotic event, such as a heart attack. However, a direct consequence of this is these patients will have a tendency to increased bleeding with surgical procedures, and this must be controlled with effective, local measures. Hence, good dental practice relies on a good understanding of therapeutics.

History of therapeutics

The practice of therapeutics is as old as history, and was well documented in ancient Greek and Egyptian civilizations. Throughout history there have been two opposing approaches to therapeutics, a magico-religious approach and an empirico-rational approach. The magico-religious approach is based upon the belief that disease is a supernatural event, and therefore should be managed by such forces, while the empirico-rational approach assumes that disease is a natural process that is best managed by a scientific approach, and evolving treatments in response to careful observation and evaluation of patient outcomes. It is this latter approach that forms the basis of current evidence-based practice.

In itself, the empirico-rational approach is not new. The father of modern medicine was the Ancient Greek physician, Hippocrates (circa 460–370 bce). Hippocrates is accredited with insisting that disease is a natural process, and should be managed in a judicious manner. Some of the most basic principles of clinical practice, such as the importance of hygiene, can be traced back to the Hippocratic Works. Hippocrates even suggested that sometimes, ‘to do nothing was the best remedy’, recognition of the capacity of the human body to fight disease and initiate repair. However, for most of the intervening period between Hippocrates and the twentieth century, the practice of therapeutics was not based upon a scientific rationale. Common practices have included treatments such as bleeding patients, not only through the use of leeches, but also by severing blood vessels. Needless to say, many of these treatments did more harm than good. In fairness, though, a key underlying issue was that the function of the human body, and the basis of disease, was so poorly understood that it impeded a more scientific approach to medicine. It was the Russian physician, Virchow, who indicated that a scientific approach to therapeutics would come through its combination with physiology, and with it an improved understanding of normal body function.