Pharmacology

DEFINITION: The science or knowledge of chemicals that affect biological processes

ANATOMY OR SYSTEM AFFECTED: Blood, brain, cells, immune system, nervous system, psychic-emotional system

Science and Profession

The science of pharmacology includes the history, source, physical and chemical properties, and biochemical and physiological effects of drugs (therapeutic chemicals, diagnostic chemicals, toxins, and related substances).

“Drug” is a noun in common usage, but it has complex meanings. “Drug” or “medicine” is often used to indicate a therapeutic substance usually obtained from a pharmacy or drugstore. “Drug” also is used to indicate an illegal substance used for mood-altering effects. Historically, people made their own drugs from materials found naturally in plants, animals, and minerals; some people continue to do so. The term “drug” in this article will focus on the meaning as it is understood by scientists called pharmacologists. Any chemical can be thought of as a drug by a pharmacologist: a drug is simply a chemical that produces a change in a biological process.

Water and oxygen can be thought of as drugs, as can foods and poisons. “Drug,” therefore, is a word to indicate an idea, concept, or perception about a chemical. When the chemical, such as oxygen, is causing a change in a biological process, then the chemical is acting as a drug. If the same chemical is causing a change in some other kind of system—for example, causing an iron rod to rust—then the chemical is not acting as a drug. Drugs may be found in nature or made by humans. Most modern chemicals used as drugs are made by humans.

The biological process that is being changed by a drug may be one occurring in a sick person. Many drugs are used therapeutically—that is, to treat diseases—but pharmacologists do not limit drugs to therapeutic chemicals. They are interested in drug effects on any biological process, even healthy ones occurring in plants and microorganisms, as well as those in animals and humans.

All drugs, even therapeutic drugs, have several effects on biological processes. Some of these effects are seen only at high concentrations. Unwanted effects, especially if they are injurious, are called adverse effects. A serious adverse effect, especially if it requires special medical treatment, may be considered a toxic reaction, or poisoning. Any chemical that produces an injurious effect, one that is detrimental to a biological process, is called a toxin. The severity of the toxic effect is based on the concentration of the toxic substance. Toxic substances in the environment are called pollutants.

The idea of drug concentration is very important. Concentration refers to the number of chemical molecules in a specified volume (such as a teaspoonful, an ounce, or a milliliter) of liquid or gas. Concentration is related to dosage and to the intensity of a drug’s effect on a biological process. It is important to remember, however, that the effect of a drug on the body may vary considerably depending on the route of administration. For instance, if one were to eat a drug, then metabolism of the drug is usually very slow, whereas if one were to inject a drug into the bloodstream, then the effects of the drug are observed quite rapidly. Therefore, when pharmacologists discuss drugs and their effects, particularly on humans, they will also frequently discuss the route of administration to make the context of the effect clear.

Concentration and the related concept of dilution are easy to understand. Two spoonfuls of sugar in a glass of water form a more concentrated solution of sugar-water than one spoonful of sugar. The more concentrated sugar-water will taste sweeter. Since taste is a biological process caused by a chemical, the chemical (sugar) can be thought of as a drug. The concentration of the chemical affects the biological process. There is a limit, however, to the sweetness of a solution. At some point, more sugar added to the solution will not increase the sensation of sweetness. Adding more sugar may result in a “toxic” reaction of nausea and even vomiting.

There are also different kinds of sugars. When one says that some are sweeter than others, one means that sweeter sugars will be just as sweet at very dilute concentrations as less-sweet sugars at very high concentrations. Thus, the first kind of sugar is said to be more potent than the second, even though the second can be just as sweet at high concentrations. Some sugars, however, will not taste very sweet regardless of the concentration. This example illustrates principles that are shared by many drugs. It is important to understand that taking a double dose of a drug will not necessarily produce a double effect. It is also important to understand that a tiny dose of one drug can have the same, or even stronger, biological effect than a large dose of a similar drug.

Most therapeutic drugs act directly on special parts of cells within the body called receptors. A receptor is part of the cell structure. A receptor for a specific drug is always located at the same place within a cell. Yet there are different kinds of receptors found at various locations in cells. Many receptors are found on the cell surface; others are found inside cells. Some receptors are found only on certain types of cells.

Each type of receptor has a specific function. When a drug “fits” a receptor, like how a key fits a lock, the receptor starts the biological process for which the drug is known. Different kinds of drugs can fit a single type of receptor, which explains why different drugs (for example, aspirin and acetaminophen) can have similar effects (relieve pain). Furthermore, one drug may be able to act on several different types of receptors. A receptor, however, can have only one biological response to all the drugs that act on it.

A drug acting on receptors in cells of one organ can affect distant organs. For example, a drug acting on brain cells may cause the nerves acting on blood vessels to increase blood pressure, which can change the heartbeat. The effect of a drug on receptors is usually temporary and should be reversible. In most cases in which a drug works through a receptor, the receptor releases the drug after the two have come together. If this release does not occur, the receptor is said to be blocked. The blockage of a receptor can be therapeutically beneficial, but it may sometimes lead to an adverse reaction.

In humans and animals, most drugs travel in the bloodstream to reach cell receptors. The drug enters the bloodstream after being applied to a body surface or after being swallowed, inhaled, or injected. The effect of the drug is eventually diminished because the body dilutes the drug, chemically alters it (so that it no longer has a pharmacological effect) and eliminates it. Chemical alteration of drugs usually occurs in the liver by a process called biotransformation. Elimination of most drugs, or their biotransformed relatives, usually occurs through the urine but may sometimes occur through secretions (sweat, tears, or breast milk), feces, or even exhaled gases.

Diagnostic and Treatment Techniques

Three examples of the use of therapeutic chemicals in the field of pharmacology are anesthesia, cardiac-enhancing drugs, and drugs that fight infections. These examples demonstrate the use of various classes of drugs and provide insight into the variety of drug actions.

Anesthetics are chemical painkillers. They are very important drugs because most diseases are accompanied by pain. Often, the first objective of a patient is to get relief from the pain, even though the anesthetic may do nothing to cure the disease. Pain is a sensation felt in the brain, not at the site of injury. Special nerves at the site of injury send a signal (nerve impulse) to the brain, where it is interpreted as pain occurring at a specific location in the body. Mild pain and severe pain are detected by different kinds of nociceptive (pain-sensing) nerves. As pain increases in severity, the brain not only perceives and interprets the pain but also sends out special autonomic signals.

Autonomic signals from the brain serve an extremely important function: They control body functions that do not require conscious thought, such as sweating, heart rate, blood pressure, digestion, and eye focus. Autonomic signals coordinate these functions and change them in response to conditions outside the body. When the body is threatened, such as when a person is frightened, autonomic signals prepare the body to fight or flee the threatening situation. The pain of surgery causes the brain to send autonomic signals to put the body in a defensive state, resulting in sweating and increases in heart rate, breathing, and blood pressure. Additionally, all the muscles of the body will become tense. This defensive state is undesirable during surgery.

Drugs used to relieve pain without causing unconsciousness are called analgesics. Mild pain can usually be controlled with an analgesic such as aspirin. More severe pain may require an opioid analgesic such as morphine. Sometimes, the term “narcotic” is used as a synonym for opioid analgesics, but that term is often used in a legal context to indicate any chemical that can cause dependence (addiction). An analgesic changes the way in which the brain interprets a nociceptive stimulus. The most severe pain, such as that during surgery, is controlled by an anesthetic. An anesthetic may act at a specific site, such as on the nerves of a tooth; a local anesthetic, such as novocaine, blocks the transmission of the nociceptive stimulus to the brain. Other anesthetics required for major surgery cause a loss of consciousness; these are called general anesthetics. As with all therapeutic drugs, the action of an anesthetic is reversible.

A general anesthetic should perform several functions: it should alter the brain’s interpretation of pain, cause a temporary amnesia that prevents remembrance of the nociceptive sensation, produce autonomic stability, and cause muscle relaxation. This is much to ask of a single drug. Therefore, general anesthesia is achieved by using several drugs, each capable of accomplishing one or more of the goals.

A general anesthetic agent usually works on nerve cells to provide pain relief and amnesia. These general functions are provided by both kinds of general anesthetics, those that are inhaled and those that are injected. Other drugs are used to control autonomic signals and to provide for muscle relaxation. When the surgery is completed, the patient returns to consciousness as the anesthetic agents are removed from the nerves. This is done by biotransformation and by excretion. Pain immediately after surgery will be controlled by an opioid analgesic. When the pain diminishes as healing progresses, it becomes milder and can be controlled with a nonopioid analgesic.

Drugs are also important in helping people recover from a myocardial infarction (heart attack). The heart is a pump that supplies blood to all cells of the body. Blood carries oxygen and nutrients to the cells and removes waste materials from them. The heart is a living muscle composed of cells, and blood vessels must supply each cell of the muscle. If a blood vessel in the heart becomes suddenly blocked, then the cells served by that blood vessel become starved and die. This is a heart attack. If only a small portion of the heart is injured, the person can survive the attack, especially if drugs are given that strengthen the heart.

An important class of drugs used to strengthen the heart is composed of the cardiac glycosides, such as digitalis. These drugs act to improve the ability of the heart cells to use calcium efficiently. Calcium is essential to maintaining a normal heartbeat. Because a heart attack is painful, it causes a defensive autonomic response from the brain. It is important to use analgesics to relieve the pain and other drugs to control the autonomic response. Another important therapy is to provide more oxygen to the heart. This is done directly by administering oxygen, but it is also done by using drugs that can remove the blockage from the blood vessel. Since the blockage usually occurs when a blood clot forms in a damaged blood vessel, drugs that dissolve clots can sometimes open the blocked vessel and restore the flow of oxygen-rich blood to the starved cells. A person recovering from a heart attack will sometimes be given drugs to prevent another blockage. Some drugs prevent fatty deposits from forming in the vessels, while others act to slow down clot formation.

Drugs used to treat infection are designed to kill cells. Infection is caused by foreign microbes attacking the body. The microbes may be viruses, bacteria, fungi, or even parasitic worms. Antimicrobial drugs (antibiotics) are given to the infected person to destroy the foreign cells without damaging the patient’s own cells. Therefore, the drug must be selectively toxic to the foreign cells. Few drugs are perfectly selective, however, and most have some toxic effects on the patient as well.

There are many ways to develop a selectively toxic drug, but selectivity usually depends on a unique feature of the invading foreign cells, such as the cell walls of bacteria. Human cells are surrounded by cell membranes. Bacteria have cell membranes as well, but they also have cell walls outside these membranes. If the bacterial cell wall is damaged, then the bacterium becomes weakened and can be killed by the body’s defense mechanisms. Penicillin is an antibiotic drug that damages the cell walls of many bacteria. Penicillin has few adverse effects on the infected person because human cells do not have cell walls. (Unfortunately, however, some people develop an allergic reaction to penicillin.)

Perspective and Prospects

In the prehistoric world, priests were called upon to intercede for persons suffering from disease and pain. As humans gained experience and developed a means of sharing that experience, especially through written records, it was noticed that certain components of the diet could reliably inflict or relieve pain; these were the first drugs. Similar effects could be obtained by inhaling natural materials or applying them to the skin through rubbing or injection. Such activities were thought to involve supernatural powers, however, and authority to use these drugs was still restricted to members of the priesthood, namely, medicine men or shamans.

Writings about the medicinal properties of natural materials can be found in Chinese, Egyptian, Greek, Indian, and Sumerian manuscripts, some of which are thought to be as much as six thousand years old. The Ebers Papyrus of Egypt (1550 BCE) contains more than eight hundred prescriptions using seven hundred drugs. It was known that some drugs were cathartics, some were diuretics, and others were purgatives, soporifics, or poisons. Yet factual knowledge about why these actions occurred was lacking, in large measure because knowledge of body function and chemistry was lacking. In this absence, people speculated that drug action was due to “essential properties” of the drug, such as warmth or wetness.

Only with the European Renaissance in the early sixteenth century was the scientific method applied to questions about the natural world, both physical and living. In 1543, Andreas Vesalius published the first complete description of human anatomy. In the early seventeenth century, William Harvey discovered the circulation of blood, and Antoni van Leeuwenhoek discovered living cells with his microscope. In the eighteenth century, the chemistry of oxygen was established by Carl Scheele, Joseph Priestley, and Antoine Lavoisier, and by the end of the century, chemical methods were becoming available to separate pure drugs from crude natural concoctions. In 1806, Friedrich W. Serturner purified morphine from the opium poppy, and in 1856, Friedrich Wöhler isolated cocaine from coca. Also of great intellectual and economic significance was the 1828 synthesis by Wöhler of urea, the first of many chemicals which heretofore had been available only from living organisms. Hormones, general anesthetics, and the bacterial cause of infectious diseases were discovered.

Until the twentieth century, drugs were discovered empirically; they existed in nature and needed to be “found.” The knowledge gained during the nineteenth century about how drugs worked enabled pharmacologists of the twentieth century to “design” drugs not found in nature. For example, Paul Ehrlich, a German scientist, announced in 1910 that he had successfully combined a dye that stains bacteria with the poison arsenic to create an antibacterial drug, arsphenamine (Salvarsan), that is highly effective in treating syphilis. In a similar way, the antibacterial sulfonamide chemicals were developed in the 1930s.

It was soon recognized that the powerful effect of pure drugs (in contrast to potions made from natural materials) had the potential to harm as well as to help, to kill, or to cure. The safe use of these drugs required special knowledge, so government agencies were established in the twentieth century to regulate drug manufacture and distribution. The original Pure Food and Drug Act, passed by the United States Congress in 1906, imposed quality controls on drug manufacturers. In 1927, Congress created the Food, Drug, and Insecticide Administration (FDIA), to enforce the 1906 law. Until 1914, any drug could be obtained without a prescription; this was changed by the Harrison Narcotic Act. Further limitations on the sale of drugs to the public came with the Food, Drug, and Cosmetic Act of 1938 and the Durham-Humphrey Amendment of 1951. The Controlled Substances Act of 1970 superseded the Harrison Narcotic Act.

With the passage of time, enforcement responsibilities were changed. The FDIA became the Food and Drug Administration (FDA) in 1931 and was transferred from the Department of Agriculture to what is now the Department of Health and Human Services. The Drug Enforcement Administration for controlled substances was established within the Justice Department.

By the twenty-first century, drugs were available to alter personality, cure some types of cancer, influence the reproductive system, and control the body’s response to foreign materials such as transplanted organs. Many of these drugs were designed using powerful computers. Drugs were even being developed to alter cellular genetics. However, such events as the American opioid epidemic in the early twenty first century raised concerns about the power and prevalence of certain prescription drugs.

Bibliography

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Parrish, Richard. Defining Drugs: How Government Became the Arbiter of Pharmaceutical Fact. Taylor and Francis, 2017.

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