Essential Dental Therapeutics

David Wray, David Wray

• Publisher: Wiley-Blackwell
• Year: 2017
• ISBN:
  9781119057420
• Edition: 1
• Topic: Medicine
• Subtopic: Dentistry

Essential Dental Therapeutics is a practical guide to drugs and their effects on dental care. Covering both medical and dental prescribing, all major categories of prescription drugs, their possible side effects, and potential drug interactions are discussed. The medical section is succinct and easily understandable, providing busy dentists with the information they need about medical conditions and the drugs used to treat them. The dental section offers practical, straightforward information that is relevant to everyday dental prescribing.

All clinical contributing authors are medically and dentally trained, and both strands are fully integrated throughout the text. Readers can test their knowledge by using the key topics and learning objectives at the start of each chapter, and by accessing the companion website featuring self-assessment questions. Essential Dental Therapeutics is a practical reference for dental students and practitioners, ensuring they are safe and informed in everyday practice.

Chapter 1
Introduction to pharmacology and therapeutics – pharmacodynamics

Alan Nimmo

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.

As mentioned earlier, the historical basis of therapeutics lay in the use of natural potions, normally of plant origin. Some of these natural agents were actually very potent and effective. Indeed, there are a number of agents in current, clinical use, which have been used, in crude form, for hundreds, and even thousands of years. Some notable examples include the analgesic, morphine, which comes from the opium poppy, and the muscarinic antagonist, atropine, which comes from the plant, deadly nightshade. Indeed, the first local anaesthetic was cocaine, which comes from the leaves of the cocoa plant. One might assume that the existence of such effective medicinal agents would facilitate a scientific approach to therapeutics but, if anything, they tended to work against it. The issue was that those agents that were effective, produced their effects in such a specific and potent manner, that it was believed their actions could not be explained in terms of physical or chemical reactions. Instead, it was assumed that they must be imbued with some kind of magical, or vital forces. It was Paul Ehrlich, at the beginning of the twentieth century, who insisted that drug action should be understood in terms of normal chemical and physical reactions. In particular, he suggested that drugs are able to produce their specific and selective effects because they bind to specific targets within the body. It is an understanding of these targets, and how drugs interact with them, that underpins modern pharmacology.

Targets for drug actions

Although there are hundreds of different drugs in clinical use, the way in which these drugs are able to produce their effects within the body is limited to a few basic mechanisms. Ehrlich suggested that drugs bind to specific target molecules, and we now recognize that these molecules are primarily key functional proteins, particularly proteins associated with communication within the body. The normal function of the body is under the control of the nervous, endocrine and paracrine systems. These systems use chemical mediators, such as neurotransmitters and hormones, to affect their control. In the same way, many drugs produce their effect by modulating this natural chemical signalling through targeting the functional proteins associated with chemical communication. The other, major way in which drugs act is by being selectively toxic, in other words they are toxic to particular cells or organisms, but are relatively innocuous to healthy human cells.

Receptors

As indicated, the key communication and control systems in the body exert their effects through the release of chemical mediators, such as neurotransmitters and hormones. These mediators are able to produce their effects on their target cells because those cells have receptors, that are not only capable of detecting chemical messages, but are also able to transduce and amplifying that signal to bring about a meaningful response within that cell. In terms of the way in which natural mediators act on these receptors, there are two components to their action. First, they bind to the receptor in question, but coupled to that, they also stimulate that receptor, to bring about a response. The ability of a messenger to bind to a particular receptor is referred to as its affinity, while the ability of the messenger to actually stimulate a receptor, and bring about a response, is referred to as efficacy. An analogy that is commonly used to describe this mechanism is the ‘lock and key’ effect. A key must not only have the correct shape to fit into a particular lock (affinity), but it must also have the precise shape that enables it to turn in the lock, and open that particular lock.

In terms of drugs, a number of drugs produce their effects by acting upon receptors, and thereby altering chemical signalling, and with it, control function within the body. Some drugs will produce their effect by mimicking the actions of the natural chemical messengers, in other words they will bind to, and stimulate the specific receptor. Those drugs, which have both affinity and efficacy for a particular receptor, are referred to as agonists. An example of a drug which acts as an agonist is salbutamol, which is used for the management of asthma. Salbutamol is an agonist for the beta2-adrenergic receptor. It mimics the natural actions of adrenaline on the beta2-receptors of airway smooth muscle, relaxing the airways, and thereby relieving an asthmatic attack.

Another way in which drugs can alter chemical signalling at receptors, is to block that receptor. If a drug binds to a receptor, but does not stimulate it, it has in itself no direct action. However, by binding to, and occupying the binding site, it can prevent the natural messenger from producing its effects at that receptor, and hence the drug can prevent a particular, unwanted response. Such drugs, which possess affinity for a receptor, but no efficacy, are referred to as antagonists. Such drugs are often identified by the prefix “anti” or the suffix “blocker”, for example antihistamines or beta-blockers. Antihistamines can be used to manage some allergic reactions, such as allergic rhinitis, or hay fever, through blocking the unwanted actions of histamine.

Enzymes

The second class of functional protein that drugs may act upon, is enzymes. Enzymes are obviously essential for catalysing metabolic reactions within the body. However, a number of enzymes are responsible for the synthesis of, and degradation of, chemical messengers. It is particularly this kind of enzyme that serves as a target for drug activity.

The eicosanoids are a family of chemical messengers that are derived from membrane phospholipids. The synthesis of these mediators begins with the liberation of arachidonic acid from membrane phospholipids by the enzyme phospholipase A₂. The arachidonic acid is then metabolized by another enzyme, cyclooxygenase, to give rise to the prostanoids (prostaglandins and thromboxanes). These lipid mediators regulate a number of physiological processes, but are also important inflammatory mediators. The most widely used anti-inflammatory drugs are the non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen. They produce their anti-inflammatory effects by inhibiting the cyclooxygenase enzyme, thereby inhibiting the production of the prostanoids.

Drugs that inhibit enzyme activity can also be used to enhance chemical signalling. Currently, the main agents used to manage Alzheimer's disease are acetylcholinesterase inhibitors. These drugs reduce the breakdown of acetylch...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• List of contributors
• Preface
• About the companion website
• Chapter 1: Introduction to pharmacology and therapeutics – pharmacodynamics
• Chapter 2: Introduction to pharmacology and therapeutics – pharmacokinetics
• Chapter 3: Introduction to pharmacology and therapeutics – drug safety
• Chapter 4: Antimicrobials – antiseptics and disinfectants
• Chapter 5: Antimicrobials – antibiotics
• Chapter 6: Antimicrobials – antifungals
• Chapter 7: Antimicrobials – antivirals
• Chapter 8: Therapeutics of pain management
• Chapter 9: Corticosteroids
• Chapter 10: Fluoride and toothpaste
• Chapter 11: Treatments for dry mouth
• Chapter 12: Therapeutics for medical emergencies in dental practice
• Chapter 13: Central nervous system 1 – mood disorders
• Chapter 14: Central nervous system 2 – neurodegenerative and acquired disorders
• Chapter 15: Central nervous system 3 – genetic and developmental disorders
• Chapter 16: Endocrine disorders 1
• Chapter 17: Endocrine disorders 2 – diabetes mellitus
• Chapter 18: Cardiovascular therapeutics
• Chapter 19: The respiratory system
• Chapter 20: Coagulation
• Chapter 21: Gastrointestinal pharmacology
• Chapter 22: Antineoplastic therapeutics
• Chapter 23: Vitamins and minerals
• Chapter 24: Musculoskeletal therapeutics
• Index
• End User License Agreement