Pharmacology Unit 1.1 Key Information

Pharmacology is the study of drugs and their action on living organisms. For nurses, a sound knowledge of basic pharmacologic principles is essential in administering medications safely and monitoring clients who receive these medications. This chapter presents a basic overview of the pharmacologic principles needed to understand medication administration. Finally, herbal medicines as they relate to pharmacology are discussed.

Over the last century, drugs have changed the way health care providers treat clients. In the early 1900s, individuals died from infections and surgical complications partly because of a lack of sanitary conditions and the fact that medicines used to combat infection did not exist at the time. One example is the discovery of drug substances (antibiotics), which changed an infection that meant certain death to now a diagnosis of a treatable acute and typically short-lived health condition. Drug therapy also means that clients lacking certain substances in their bodies, such as insulin, or those diagnosed with cancerous tumors can now live long and productive lives.

Medications are substances derived from natural sources, such as plants and minerals, or they are synthetically produced in a laboratory. An example of a drug derived from a natural source is digitalis, which is an extract from the foxglove plant that acts as a potent heart medication. Mipomersen (brand name Kynamro) is a chemically engineered drug designed to target specific cell components in people with high cholesterol.

o begin understanding the principles of pharmacology, let us start with learning about how drugs are named. Once you understand this concept, it will be easier to understand classes and categories of drugs, as well as federal regulations pertaining to drugs and how they are developed. Throughout the process of development, drugs may have several names assigned to them. These different names can be confusing. Therefore, if you have a clear understanding of the different names used, you can promote client safety by reducing errors.

A drug may have three different names:

Chemical name—a scientific term that describes the molecular structure of a drug; it typically is the chemical component of the drug.

Generic name—considered the official name of a drug and is the name given to a drug that can be made or marketed by any company; it is nonproprietary, meaning it is not owned by any specific agency.

Trade name—selected by a specific company producing the drug for marketing purposes. When a drug name is followed by a trademark symbol ™ or a registered trademark symbol ®, this signifies that it is the trade or brand name.

The generic name is the official name that is given to a drug by the US Food and Drug Administration (FDA). It also is the name found in the National Formulary or the US Pharmacopeia for an approved drug. To avoid confusion, it is best to use the generic name. One safety practice is the use of Tall man lettering for drugs that look or sound alike. Using capital letters within the name of a drug helps health care providers to distinguish different drugs that have similar or confusing names.

Different organizations classify drugs for different reasons. Medicare and Insurance companies classify drugs in a tier system for cost and coverage purposes. The Drug Enforcement Agency (DEA) defines drugs according to legality. In our study of pharmacology, we are going to look at how drugs are developed by pharmaceutical companies, named, and then classified.

Drugs are organized into different classes and categories to help people better understand how they work in the body. A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes. For instance, in Unit 2, drugs that retard or destroy pathogens are classified as anti-infectives. In each chapter, these drugs are further categorized by the way they work (such as antivirals) or their chemical structure (e.g., penicillins). In addition, once a drug is approved for use, the FDA assigns it to one of the following categories: prescription, nonprescription, or controlled substance. This method of assignment helps you to understand the ease of accessibility of a drug to the client.

Prescription drugs, also called legend drugs, are the largest category of drugs. Prescription drugs are prescribed by a licensed health care provider. The prescription (Fig. 1.1) contains the name of the drug, the dosage, the method and times of administration, and the electronic signature of the licensed health care provider prescribing the drug. Typically, the health care provider writes the prescription electronically and it is transmitted to the pharmacy. A paper copy may be printed for a client if a pharmacy outside the health care system will be used to obtain the medication.

Drugs requiring prescription are designated as such by the federal government because they are potentially harmful unless their use is supervised by a licensed health care provider, such as a nurse practitioner, physician, or dentist. Supervision is important because, although these drugs have been tested for safety and therapeutic effect, prescription drugs may cause different reactions in some individuals.

In institutional settings, the nurse administers the drug and monitors the client for therapeutic effect and adverse reactions (undesirable effect). Some drugs have the potential to be toxic (harmful). As a nurse, you will play a critical role in evaluating the client for toxic effects. When these drugs are prescribed to be taken at home, you will provide client and family education about the drug.

Nonprescription drug designation is made by the FDA when the drug is safe (taken as directed) and obtainable without a prescription. These drugs are frequently called over-the-counter (OTC) drugs and may be purchased without a prescription in a variety of settings, such as a drugstore, local supermarket, or a large warehouse retailer (e.g., Costco or Sam’s Club). OTC drugs include those given for symptoms of the common cold, minor aches and pains, constipation, diarrhea, heartburn, and minor fungal infections.

Labeling requirements give the consumer important information regarding the drug, dosage, contraindications, precautions, and adverse reactions. Consumers are urged to read the directions carefully before taking OTC drugs. Yet, these drugs are not without risk. For example, acetaminophen, commonly used for pain relief, is also found in many OTC products, such as cough and cold remedies. When taken for both pain and in a cold remedy, this accumulative amount of the drug can potentially harm a person’s liver.

Controlled substances are the most carefully monitored class of drugs. These drugs have a high potential for abuse and may cause physical or psychological dependency. Physical dependency is defined as the habitual use of a drug in which negative physical withdrawal symptoms result from abrupt discontinuation; it is the body’s dependence on repeated administration of a drug. Psychological dependency is a compulsion or craving to use a substance to obtain a pleasurable experience. It is the mind’s desire for the repeated administration of a drug. Physical and psychological dependence do not always occur together, yet one type of dependency may lead to the other.

The Controlled Substances Act of 1970 established a classification system for drugs with abuse potential. The act regulates the manufacture, distribution, and dispensing of these drugs. The Controlled Substances Act divides drugs into five groups, called schedules, which are based on the substance’s potential for abuse and physical and psychological dependence. Appendix A describes the five schedules.

Prescription practices of the primary health care provider for controlled substances are monitored by the DEA. Under federal law, limited quantities of certain schedule V drugs may be purchased without a prescription, with the purchase recorded by the dispensing pharmacist. In some cases, state laws are more restrictive than federal laws and impose additional requirements for the sale and distribution of controlled substances. In hospitals or other agencies that dispense controlled substances, the scheduled drugs are counted every 8–12 hr to account for each injectable, tablet, or other form of the drug. Any discrepancy in the number of drugs must be investigated and explained immediately.

Drug development is a long and arduous process that can take from 7–12 years, and sometimes longer. The FDA has the responsibility for approving new drugs and monitoring drugs currently in use for adverse or toxic reactions. The development of a new drug is divided into the pre-FDA phase and the FDA phase. During the pre-FDA phase, a manufacturer conducts in vitro testing (testing in an artificial environment, such as a test tube) using animal and human cells to discover new drug compounds. This testing is followed by studies in live animals. The manufacturer then makes application to the FDA for Investigational New Drug (IND) status.

During the FDA phase, clinical (i.e., human) testing of the new drug begins. Clinical testing consists of three phases, with each phase involving a larger number of people (Fig. 1.2). In all phases the effects, both pharmacologic and biologic, are studied. Phase 1 involves 20–100 individuals who are healthy volunteers. This phase of testing is designed to see what the drug substance does to healthy tissue. If Phase 1 studies are successful, the testing moves to Phase 2, where the drug is given to people who have the disease or condition for which the drug is thought to be effective. If those results are positive for helping to reduce or eliminate the problem and adverse reactions are not too great, the testing progresses to Phase 3, in which the drug is given to large numbers of clients in medical research centers to provide information about adverse reactions. Phase 3 studies offer additional information on dosing and safety. Because of this extensive process, clinical trial studies can extend for many years.

A New Drug Application (NDA) is submitted after the investigation of the drug in Phases 1, 2, and 3 is complete and the drug is found to be safe and effective. With the NDA, the manufacturer submits all data collected concerning the drug during the clinical trials. A panel of experts, including pharmacologists, chemists, physicians, and other professionals, reviews the application and makes a recommendation to the FDA. The FDA then either approves or denies approval of the drug for use. This process can cost well over a billion dollars for a successful drug and take up to 12 years to be ready for marketing to the public (Lim, 2019). Although the cost of drugs is not covered in this textbook, it is of primary concern to many of the clients you will come into contact with during your career as a nurse.

After FDA approval, the company making the drug will give the new drug a brand name. This allows the company to sell the specific drug using this name for a limited time. The hope is that some of the research and development cost will be defrayed by the sales of this brand name drug. After the specified time, other companies may sell the drug using the generic name. The brand name is reserved for the company that first produced the specific drug substance.

After FDA approval, continued surveillance is done to ensure safety. Postmarketing surveillance (Phase 4) occurs after the manufacturer places the drug on the market. During this surveillance, an ongoing review of the drug occurs with particular attention given to adverse reactions. Health care providers are encouraged to help with this surveillance by reporting adverse effects of drugs to the FDA by using MedWatch (Box 1.1) or the Institute for Safe Medication Practices Medication Errors Reporting System.

Although it takes considerable time for most drugs to get FDA approval, the FDA has special programs to meet different needs. Examples of these special programs include:

Orphan drug program

Accelerated programs for urgent needs

Risk Evaluation and Mitigation Strategies (REMS) program

The Orphan Drug Act of 1983 was passed to encourage the development and marketing of products used to treat rare diseases. The act defines a rare disease as a condition affecting fewer than 200,000 individuals in the United States or a condition affecting more than 200,000 persons in the United States but for which the cost of producing and marketing a drug to treat the condition would not be recovered by sales of the drug.

The National Organization of Rare Disorders reports (2019) that there are more than 7000 rare disorders that affect approximately 30 million individuals. Examples of rare disorders include amyloidosis, Gaucher disease, and phenylketonuria.

The act provides for incentives such as research grants, protocol assistance by the FDA, and special tax credits to encourage manufacturers to develop orphan drugs. If the drug is approved, the manufacturer has 7 years of exclusive marketing rights. More than 1,700 new drugs and biologics have received FDA approval since the law was passed. Examples of orphan drugs include Velcade for multiple myeloma, Cerezyme—enzyme replacement therapy for Gaucher disease, and Valstar for the treatment of bladder cancer.

Accelerated approval of drugs is offered by the FDA as a means to make promising products for life-threatening diseases available on the market, based on preliminary evidence and before formal demonstration of client benefit. The approval that is granted is considered a “provisional approval,” with a written commitment from the pharmaceutical company to complete clinical studies that formally demonstrate client benefit. If the drug continues to prove beneficial, the process of approval is accelerated.

Acquired immunodeficiency syndrome (AIDS) is an example of a disease that qualified as posing a significant health threat, and finding new drugs qualified for the accelerated program. When first discovered, AIDS was very devastating to the individuals affected and health agencies feared the danger the disease posed to public health. Therefore, the FDA and pharmaceutical companies worked together to shorten the IND approval process for drugs that showed promise in treating AIDS. This accelerated process allowed primary health care providers to administer medications that indicated positive results in early Phase 1 and 2 clinical trials, rather than wait until final approval was granted. HIV is now viewed as a chronic disease, partly because of the efforts of accelerating the clinical trial process for drugs to treat AIDS.

The COVID-19 vaccine development is another example. Emergency use authorization was granted to two organizations (Pfizer-BioNTech and Moderna) within less than 1 year (Solis-Moreira, 2020). Owing to the pandemic nature of the SARS-CoV-2 pathogen, research and clinical trials were carried out in tandem and not sequentially, reducing the time needed to prepare the vaccines for market when international research and funding was provided (Solis-Moreira, 2020).

The Risk Evaluation and Mitigation Strategies (REMS) program is designed to monitor drugs that have higher risk to the client compared with benefit. To use a drug included in this program, there are specific educational requirements of the health care providers (prescribing and administering techniques) and education and monitoring for clients taking the drug. Therefore, only HCP-trained, enrolled, and certified providers may prescribe drugs with REMS restrictions. You can see the restrictions placed upon these drugs in a REMS program by visiting the brand name drug’s website.

Having learned about the naming and development of drugs, we turn to how drugs work. Once in the body, drugs act in certain ways or phases. Oral drugs go through three phases: the pharmaceutic phase, pharmacokinetic phase, and the pharmacodynamic phase (Fig. 1.3). Because liquid and parenteral drugs (drugs given by injection) are already in a fluid form they only go through the latter two phases, bypassing phase one entirely.

In the pharmaceutic phase, the drug is dissolved. Drugs must be a soluble liquid to be absorbed by the body. Drugs that are liquid or drugs given by injection (parenteral drugs) are already dissolved and are absorbed quickly. A tablet or capsule (solid forms of a drug) goes through this phase in the gastrointestinal (GI) tract as it disintegrates into small particles and dissolves into the body fluids. Tablets that have an enteric coating and time-release capsules do not disintegrate until they reach the alkaline environment of the small intestine.

Pharmacokinetics refers to the transportation activity of drugs in the body after administration. These activities include absorption, distribution, metabolism, and excretion. These phases can be broken down into subphases such as transport, first-pass effect during absorption, and half-life during excretion of the drug

Absorption is the process by which a drug is made available for use in the body. This process involves moving the drug from the site of administration into the body fluids. It occurs after the solid form (e.g., a pill or tablet) of the drug dissolves or after the administration of an oral liquid or parenteral drug. During this process, the drug particles in the GI tract are moved into the body fluids. This movement can be accomplished in several ways:

Active transport—cellular energy is used to move the drug from an area of low concentration to one of high concentration.

Passive transport—no cellular energy is used as the drug moves from an area of high concentration to an area of low concentration (small molecules diffuse across the cell membrane).

Pinocytosis—cells engulf the drug particle (the cell forms a vesicle to transport the drug across the cell membrane and into the cell).

Several factors influence the rate of absorption, including the route of administration, the solubility of the drug, and specific conditions of the body’s tissues. The most rapid route of drug absorption occurs when the drug is given by the intravenous (IV) route. When 100% of the drug given is available to the cells of the body, this is called bioavailability. Absorption occurs more slowly when the drug is administered orally, intramuscularly, or subcutaneously. This is because the complex membranes of the GI mucosal layers, muscle, and skin delay drug passage. Conditions in the body, such as lipodystrophy (the atrophy of subcutaneous tissue from repeated subcutaneous injections) inhibit absorption of a drug given in the affected site. This can occur when clients have to administer drugs repeatedly into the skin tissue, such as insulin administration for diabetes.

Another factor effecting absorption is the first-pass effect. When a drug is absorbed by the small intestine, it passes first into the liver before being released to circulate within the rest of the body. The liver metabolizes (or filters out) a significant amount of the drug before releasing it into the body. When the drug is released into the circulation from the liver, the remaining amount of active (or available) drug may not be enough to produce a therapeutic effect, and the client will need a higher dosage.

Once in the systemic circulation a drug is transported and distributed to various body tissues or target sites. Distribution of an absorbed drug in the body depends on:

Blood flow—a drug is distributed quickly to areas with a large blood supply, such as the heart, liver, and kidneys. In other areas, such as the internal organs, skin, and muscle, distribution of the drug occurs more slowly.

Solubility—the drug’s ability to cross the cell membrane affects its distribution. Lipid-soluble drugs easily cross the cell membrane, whereas water-soluble drugs do not.

Protein binding—when a drug travels through the blood, it comes into contact with proteins such as the plasma protein albumin. The drug can remain free in the circulation or bind to the protein. Only free drugs can produce a therapeutic effect. Drugs bound to protein are pharmacologically inactive. Only when the protein molecules release the drug can the drug diffuse into the tissues, interact with receptors, and produce a therapeutic effect. A drug is said to be highly protein bound when more than 80% of the circulating drug is bound to protein.

Metabolism, also called biotransformation, is the process by which the body changes a drug to a more or less active form that can be excreted. A metabolite is the inactive form of the original drug. In some drugs, one or more of the metabolites may have some drug activity. Metabolites may undergo further metabolism or may be excreted from the body unchanged. Most drugs are metabolized by the liver, although the kidneys, lungs, plasma, and intestinal mucosa also aid in the metabolism of drugs.

Two important elements of elimination of drugs from the body are:

Excretion—removal of drugs by the kidneys or the intestine.

Half-life—the time required for the body to eliminate 50% of a drug.

After the liver renders drugs inactive, the circulatory system takes these products to the kidney where the inactive compounds are excreted from the body. Other drugs are eliminated in sweat, in breast milk, or by breath or by the GI tract through feces. Some drugs are excreted unchanged by the kidney without liver involvement; because this happens it can put undue stress on the kidney. Clients with kidney disease may require a dosage reduction and careful monitoring of kidney function. Children have immature kidney function and may require dosage reduction and kidney function tests during drug therapy. Similarly, older adults have diminished kidney function and require careful monitoring and lower dosages.

Half-life refers to the time required for the body to eliminate 50% of the drug. Knowledge of the half-life of a drug is important in planning the frequency of dosing. Drugs with a short half-life (2–4 hr) need to be administered frequently, whereas drugs with a long half-life (21–24 hr) require less frequent administration. For example, digoxin (Lanoxin) has a long half-life (36 hr) and requires once-daily dosing. However, aspirin has a short half-life and requires frequent dosing. It takes five to six half-lives to eliminate approximately 98% of a drug from the body. Although half-life is fairly stable, clients with liver or kidney disease may have problems excreting a drug. Difficulty in excreting a drug increases the half-life and the risk of toxicity, because these organs do not remove the substances and the drug remains in the body longer. Older clients or clients with impaired kidney or liver function require frequent diagnostic tests measuring renal or hepatic function.

Three additional factors influence the therapeutic action of a drug and in turn determine the timing of drug administration. These factors are important when considering how a drug acts in the body:

Onset of action—time between administration of the drug and onset of its therapeutic effect.

Peak concentration—when absorption rate equals the elimination rate (not always the time of peak response).

Duration of action—length of time the drug produces a therapeutic effect.

These factors are taken into consideration when determining the dose schedule of a specific drug. This ensures that proper blood levels are maintained in the body for the drug to work properly.

Pharmacodynamics is the study of the drug mechanisms that produce biochemical or physiologic changes in the body. Pharmacodynamics deals with the drug’s action and effect in the body. After administration, most drugs enter the systemic circulation and expose almost all body tissues to possible effects of the drug. This exposure in all tissue causes the drug to produce more than one effect in the body.

Primary effect—the desired or therapeutic effect on targeted tissue or organ.

Secondary effects—all other effects, desirable or undesirable, produced by the drug.

Most drugs have an affinity for certain organs or tissues and exert their greatest action at the cellular level on those specific areas, which are called target sites. A drug exerts its action by one of two main mechanisms:

Alteration in cellular function

Alteration in cellular environment

Most drugs act on the body by altering cellular function. A drug cannot completely change the function of a cell, but it can alter the cell’s function. A drug that alters cellular function can increase or decrease certain physiologic functions, such as increasing heart rate, decreasing blood pressure, or increasing urine output.

Many drugs act through drug–receptor interaction. The function of a cell is altered when a drug interacts with a receptor. This occurs when a drug molecule selectively joins with a reactive site—the receptor—on the surface of a cell. When a drug binds to and interacts with the receptor, a pharmacologic response occurs. This process is explained in greater depth in Units 4 and 5.

An agonist is a drug that binds with a receptor and stimulates the receptor to produce a therapeutic response; antidepressants are drugs that work this way. An antagonist is a drug that joins with receptors but does not stimulate the receptors. The therapeutic action in this case consists of blocking the receptor’s function, an opioid reversal drug works in this way.

The number of available receptor sites influences the effects of a drug. When only a few receptor sites are occupied, although many sites are available, the response will be small. When the drug dose is increased, more receptor sites are used, and the response increases. When only a few receptor sites are available, and once all the receptor sites are used, the response does not increase when more of the drug is administered. However, not all receptors on a cell need to be occupied for a drug to be effective. Some extremely potent drugs are effective even when the drug occupies few receptor sites.

Some drugs act on the body by changing the cellular environment, either physically or chemically. Physical changes in the cellular environment include changes in osmotic pressure, lubrication, absorption, or the conditions on the surface of the cell membrane.

An example of a drug that changes osmotic pressure is mannitol, which produces a change in the osmotic pressure in brain cells, causing a reduction in cerebral edema. A drug that acts by altering the cellular environment by lubrication is sunscreen. An example of a drug that acts by altering absorption is activated charcoal, which is administered orally to absorb a toxic chemical ingested into the GI tract. The stool softener docusate is an example of a drug that acts by altering the surface of the cellular membrane. Docusate has emulsifying and lubricating activity that lowers the surface tension in the cells of the bowel, permitting water and fats to enter the stool. This softens the fecal mass, allowing easier passage of the stool.

Chemical changes in the cellular environment include inactivation of cellular functions or alteration of the chemical components of body fluid, such as a change in the pH. For example, antacids neutralize gastric acidity in clients with peptic ulcers.

Other drugs, such as some anticancer drugs and some antibiotics, have as their main site of action the cell membrane and various cellular processes. They incorporate themselves into the normal metabolic processes of the cell and cause the formation of a defect, such as a weakened cell wall, which results in cell death, or reduces a needed energy substrate that leads to cell starvation and death.

Most pharmacodynamic mechanisms deal with principles that affect each cell in the same way, whereas pharmacogenomics is the study of how people’s responses to medications are variable because of individual genetic variation. The genetic makeup of a person can affect the pharmacodynamics of a drug. This discovery was made during the Human Genome Project when many scientists were able to determine the different components of the human genetic code. One example is the way some individuals respond to the drug warfarin. This is a drug taken to reduce the chance of blood clots and is a blood thinner. Clients with a specific gene duplication who take warfarin are more likely to bleed when taking the average dose of the drug. This pharmacological response to a genetic variation is discussed in Chapter 36.

Pharmacogenetics (a subcategory of the above) is the study of differences in body function due to genetic differences and how that impacts the creation of individualized drug therapy that allows for the best choice and dose of drugs (Saini et al., 2010).

With the abundance of self-help information on the Internet, women of childbearing age are bombarded with a large amount of information regarding drug use, pregnancy, and lactation. In general, most drugs are contraindicated during pregnancy and lactation unless the potential benefits of taking the drug outweigh the risks to the fetus or the infant. Pregnant woman should not take any drug, legal or illegal, prescription or nonprescription, unless the drug is prescribed or recommended by the primary health care provider. Children born of mothers using addictive drugs, such as methamphetamine or oxycontin, often are born with a dependency to the drug used by the mother. Although promoted as a natural substance, herbal supplements can act like drugs, too. Women should not take an herbal supplement without discussing it first with the primary health care provider.

Smoking tobacco or drinking any type of alcoholic beverage carries risks and should be eliminated for the duration of pregnancy. Drinking alcohol is associated with risks of low birth weight, premature birth, and fetal alcohol syndrome. Inhalation of substances other than tobacco, such as electronic cigarettes or marijuana, have not been studied to the extent of making recommendations, yet most health care providers do not recommend use because of potential effects on the fetus.

Both expectant mothers and drug manufactures are concerned about the risk of causing birth defects in the developing fetus. The use of any medication (prescription or nonprescription) carries this risk, particularly during the first trimester (3 months), when the drug may have teratogenic effects. A teratogen is any substance that causes abnormal development of the fetus, often leading to severe deformation or fetal death. Drugs known to cause fetal abnormalities are classified as teratogens.

In 2015, requirements for prescribing information to health care professionals by manufacturers changed. Subheadings within the Pregnancy and Lactation subsections of drug labels such as risk summary, clinical considerations, and data were now required. The old system to assign a drug’s risk during pregnancy and breastfeeding used the letter categories of A, B, C, D, and X to classify the amount of risk to the developing fetus; to date, the new classification system is still transitioning into place and in many monographs you will see both the old letter system and the new informational system used. Therefore, the older letter-based system is provided as reference for you in Appendix A.

The letter categories for drug labeling have been in use since the 1970s and were often misinterpreted as a grading system of risk. The new method provides explanations, based on available information, about the potential benefits and risks for the mother, the fetus, children who are breastfeeding, and women and men of reproductive age. The new system will be used as new drugs are introduced to the market and as older drugs are reviewed by the FDA; therefore, you will see the old system in this text and in drug information resources as well as the new categories as they are developed.

A number of drugs are excreted in breast milk. Therefore, if a mother is lactating (breastfeeding), some of the drug she is taking will travel through her to the infant or child via the breast milk to be ingested and absorbed. It is important for both mothers and nurses to know the potential of exposure to a breastfeeding child when the mother is taking a drug.

The National Library of Medicine provides a free online database with information on drugs and lactation called LactMed (http://www.ncbi.nlm.nih.gov/books/NBK501922/). This website is geared to the health care practitioner and nursing mother and contains over 1,100 drug records. It includes information such as maternal levels in breast milk, infant levels in blood, and potential effects in breastfeeding infants. A pharmacist, Dr. Thomas Hale, from Texas Tech University has developed a system of lactation risk categories similar to that of the FDA pregnancy risk categories for drugs. Drugs are assigned an L1 to L5 risk according to the drug’s transmission in breast milk and the effect it may have on the child. Hale’s listing of certain drugs may differ from those published by organizations such as the American Academy of Pediatrics, yet it is a good starting point for discussion with mothers who are breastfeeding.

Drugs produce many reactions in the body beyond the intended reaction. The following sections discuss adverse drug reactions, allergic drug reactions, drug idiosyncrasy, drug tolerance, cumulative drug effect, and toxic reactions.

Clients may experience one or more adverse reactions or side effects when they are given a drug. Adverse reactions are undesirable drug effects. Adverse reactions may be common or may occur infrequently. They may be mild, severe, or life-threatening. They may occur after the first dose, after a few doses, or after many doses. Often, an adverse reaction is unpredictable, although some drugs are known to cause certain adverse reactions in many clients. Often these reactions affect the GI system. For example, drugs used in treating cancer are very toxic and are known to produce adverse reactions in many clients receiving them. Other drugs produce adverse reactions in fewer clients. Some adverse reactions are predictable, but many adverse drug reactions occur without warning.

Some texts use both the terms side effects and adverse reactions, using side effects to explain mild, common, and nontoxic reactions and adverse reactions to describe more severe and life-threatening reactions. For the purposes of this text and to avoid confusion, only the term adverse reaction is used, with the understanding that these reactions may be mild, severe, or life-threatening and will be defined as such.

An allergic reaction is a hypersensitive response of the immune system. Allergy to a drug usually begins to occur when more than one dose of the drug has been given. On occasion, the nurse may observe an allergic reaction the first time a drug is given, because the client has been exposed to the drug in the past.

A drug allergy occurs because the individual’s immune system responds to the drug as a foreign substance called an antigen. When the body responds to the drug as an antigen, a series of events occurs in an attempt to render the invader harmless. Lymphocytes respond by forming antibodies (protein substances that protect against antigens). Common allergic reactions occur when the individual’s immune system responds aggressively to the antigen. Chemical mediators released during the allergic reaction produce symptoms ranging from mild to life-threatening.

Even a mild allergic reaction produces serious effects if it goes unnoticed and the drug is given again. Any indication of an allergic reaction is reported to the primary health care provider before the next dose of the drug is given. Serious allergic reactions require contacting the primary health care provider immediately, because emergency treatment may be necessary.

Some allergic reactions occur within minutes (even seconds) after the drug is given; others may be delayed for hours or days. Allergic reactions that occur immediately often are the most serious.

Allergic reactions are manifested by a variety of signs and symptoms observed by the nurse or reported by the client. Examples of some allergic symptoms include itching, various types of skin rashes, and hives (urticaria). Other symptoms include difficulty breathing, wheezing, cyanosis, a sudden loss of consciousness, and swelling of the eyes, lips, or tongue.

Anaphylactic shock is an extremely serious allergic drug reaction that usually occurs shortly after the administration of a drug to which the individual is sensitive. This type of allergic reaction requires immediate medical attention.

An anaphylactic reaction should be considered if all or only some of these symptoms are present. Anaphylactic shock can be fatal if the symptoms are not identified and treated immediately. The treatment goal is to raise the blood pressure, improve breathing, restore cardiac function, and treat other symptoms as they occur. Epinephrine (adrenalin) may be given by subcutaneous injection in the upper extremity or thigh and may be followed by a continuous IV infusion. Hypotension and shock may be treated with fluids and vasopressors. Bronchodilators are given to relax the smooth muscles of the bronchial tubes. Antihistamines and corticosteroids may also be given to treat urticaria and angioedema (swelling). These are all drugs you will learn about in subsequent chapters of this book.

Angioedema (angioneurotic edema) is another type of allergic drug reaction. It is manifested by the collection of fluid in subcutaneous tissues. Areas that are most commonly affected are the eyelids, lips, mouth, and throat, although other areas also may be affected. Angioedema can be dangerous when the mouth and throat are affected because the swelling may block the airway and asphyxia may occur. Difficulty in breathing and swelling in any area of the body are reported immediately to the primary health care provider.

Drug idiosyncrasy is a term used to describe any unusual or atypical reaction to a drug. It is any reaction that is different from the one normally expected from a specific drug and dose. For example, a client may be given a drug to help them sleep (e.g., a hypnotic). Instead of falling asleep, the client remains wide awake and shows signs of nervousness or excitement. This response is idiosyncratic because it is different from what one expects from this type of drug. Another client may receive the same drug and dose, fall asleep, and after 8 hr be difficult to awaken. This, too, is abnormal and describes an overresponse to the drug.

The cause of drug idiosyncrasy is not clear, although study in the science of genetics can give us insight into possible explanations. The inability to tolerate certain chemicals and drugs is believed to be because of a genetic deficiency. Pharmacogenetics, the study of ways that specific genes can enhance sensitivity or resistance to certain drugs, helps to explain some drug idiosyncrasies. A pharmacogenetic disorder is a genetically determined abnormal response to normal doses of a drug. This abnormal response occurs because of inherited traits that cause abnormal metabolism of drugs. For example, individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency have abnormal reactions to a number of drugs. These clients exhibit varying degrees of hemolysis (destruction of red blood cells) when these drugs are administered. More than 100 million people are affected by this disorder. Examples of drugs that cause hemolysis in clients with a G6PD deficiency include aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and the sulfonamides.

Drug tolerance is a term used to describe a decreased response to a drug, requiring an increase in dosage to achieve the desired effect. Drug tolerance may develop when a client takes certain drugs, such as opioids and antianxiety drugs, for a long time. The individual who takes these drugs at home increases the dose when the expected drug effect does not occur. The development of drug tolerance is a sign of physical drug dependence. Drug tolerance may also occur in the hospitalized client. When the client begins to ask for the drug at more frequent intervals, the nurse needs to assess whether the dose is not adequate based on the disease process or whether the client is building a tolerance to the drug’s effects.

A cumulative drug effect may be seen especially in those people with liver or kidney disease because these organs are the major sites for the breakdown and excretion of most drugs. This drug effect occurs when the body is unable to metabolize and excrete one (normal) dose of a drug before the next dose is given. Thus, if a second dose of the drug is given, some drug from the first dose remains in the body. A cumulative drug effect can be serious because too much of the drug can accumulate in the body and lead to toxicity.

Clients with liver or kidney disease are usually given drugs with caution because a cumulative effect may occur. When the client is unable to excrete the drug at a normal rate, the drug accumulates in the body, causing a toxic reaction. Sometimes, the primary health care provider lowers the dose of the drug to prevent a toxic drug reaction.

Most drugs can produce toxic or harmful reactions if administered in large dosages or when blood concentration levels exceed the therapeutic level. Toxic levels build up when a drug is administered in doses that exceed the normal level or if the client’s kidneys are not functioning properly and cannot excrete the drug. Some toxic effects are immediately visible; others may not be seen for weeks or months. Some drugs, such as lithium or digoxin, have a narrow margin of safety, even when given in recommended dosages. It is important to monitor these drugs closely to detect and avoid toxicity.

Drug toxicity can be reversible or irreversible, depending on the organs involved. Damage to the liver may be reversible because liver cells can regenerate. However, the anti-infective drug, streptomycin, may cause permanent hearing loss due to its toxic effect on the eighth cranial nerve. Sometimes drug toxicity can be reversed by administering another drug that acts as an antidote. For example, when too much opiate is taken, the drug naloxone (Narcan) may be given to counteract the effect.

When testing, carefully monitor the client’s blood level of drug to ensure that the level remains within the therapeutic range. Any deviation should be reported to the primary health care provider. Because some drugs can cause toxic reactions even in recommended doses, you should be aware of the signs and symptoms of toxicity of commonly prescribed drugs.

Drug developers are researching ways to target cell structures and selected cells to minimize reactions in other body tissues, thereby reducing or eliminating adverse reactions. Genetic specialists search for genetic variations associated with drug efficiency. One of the goals of pharmacogenomics is the creation of drugs that can be tailor-made for individuals, target specific cells in the body, and adapt to each person’s own individual genetic makeup.

It is important when administering medications to be aware of the various drug interactions that can occur, especially drug–drug interactions and drug–food interactions. This section gives a brief overview of drug interactions. Specific drug–drug and drug–food interactions are discussed in subsequent drug specific chapters.

A drug–drug interaction occurs when one drug interacts with or interferes with the action of another drug. For example, taking an antacid with oral tetracycline causes a decrease in the effectiveness of the tetracycline. The antacid chemically interacts with the tetracycline and impairs its absorption into the bloodstream, thus reducing the effectiveness of the tetracycline. Drug categories known to cause interactions with other drugs include oral anticoagulants, oral hypoglycemics, anti-infectives, antiarrhythmics, cardiac glycosides, and alcohol. Drug–drug interactions can produce effects that are additive, synergistic, or antagonistic; these reactions are explained below.

Additive Drug Reaction

An additive drug reaction occurs when the combined effect of two drugs is equal to the sum of each drug given alone. The equation 1 + 1 = 2 is sometimes used to illustrate the additive effect of drugs.

Example—taking the drug heparin with alcohol will increase bleeding.

Synergistic Drug Reaction

Drug synergism occurs when drugs interact with each other and produce an effect that is greater than the sum of their separate actions. The equation 1 + 1 = 3 may be used to illustrate synergism.

Example—when a person takes both a hypnotic and alcohol. When alcohol is taken shortly before or after the hypnotic drug, the action of the hypnotic increases considerably. The individual experiences a drug effect that is greater than each drug taken alone. On occasion, the occurrence of a synergistic drug effect is serious and even fatal.

Antagonistic Drug Reaction

An antagonistic drug reaction occurs when one drug interferes with the action of another, causing neutralization or a decrease in the effect of one of the drugs. The equation 1 − 1 = 0 may be used to illustrate antagonistic reactions.

Example—protamine is a heparin antagonist. This means that the administration of protamine completely neutralizes the effects of heparin in the body and blood clotting will happen in the body.

Drug–Food Interactions

When a drug is given orally, food may impair or enhance its absorption. A drug taken on an empty stomach is absorbed into the bloodstream more quickly than when the drug is taken with food in the stomach. Some drugs (e.g., captopril) must be taken on an empty stomach to achieve an optimal effect. Drugs that should be taken on an empty stomach are administered 1 hr before or 2 hr after meals.

Other drugs, especially drugs that irritate the stomach, result in nausea or vomiting, or cause epigastric distress, are best given with food or meals. This minimizes gastric irritation. The NSAIDs and salicylates are examples of drugs that are given with food to decrease epigastric distress.

Still other drugs combine with a food and may form an insoluble food–drug mixture. For example, when tetracycline is administered with dairy products, a drug–food mixture is formed that is not absorbable by the body. When a drug cannot be absorbed by the body, no pharmacologic effect occurs.

Components in foods may also prevent the medication from working. An enzyme in the human body that breaks down many drugs is prevented from working when people eat grapefruit.

FACTORS INFLUENCING DRUG RESPONSE

Certain factors may influence drug response and are considered when the primary health care provider prescribes and the nurse administers a drug. These factors include age, weight, sex, disease, and route of administration.

Age

The age of the client may influence the effects of a drug. Infants and children usually require smaller doses of a drug than adults. Immature organ function, particularly of the liver and kidneys, can affect the ability of infants and young children to metabolize drugs. An infant’s immature kidneys impair the elimination of drugs in the urine. Liver function is not yet fully developed in infants and young children. Drugs metabolized by the liver may produce more intense effects for longer periods. Parents must be taught the potential problems associated with administering drugs to their children. For example, a safe dose of a nonprescription drug for a 4-year-old child may be dangerous for a 6-month-old infant.

Elderly clients may also require smaller doses, although this may depend on the type of drug administered. For example, the elderly client may be given the same dose of an antibiotic as a younger adult. However, the same older adult may require a smaller dose of a drug that depresses the central nervous system, such as an opioid. Changes that occur with aging affect the pharmacokinetics (absorption, distribution, metabolism, and excretion) of a drug. Any of these processes may be altered because of the physiologic changes that occur with aging. Table 1.3 summarizes the changes that occur with aging and their possible pharmacokinetic effects.

Polypharmacy is the taking of numerous drugs that can potentially react with one another. This is seen particularly in elderly clients who may have multiple chronic diseases; polypharmacy leads to an increase in the number of potential adverse reactions. Although multiple drug therapy is necessary to treat certain disease states, it always increases the possibility of adverse reactions. You need good assessment skills to detect any problems when monitoring the geriatric client’s response to drug therapy.

Weight

In general, standard dosages are based on a weight of approximately 77 kg (170 lb), which is calculated to be the average weight of men and women. A drug dose may sometimes be increased or decreased because the client’s weight is significantly higher or lower than this average. With opioids, for example, higher- or lower-than-average dosages may be necessary, depending on the client’s weight, to produce relief of pain.

Sex

The sex of an individual may influence the action of some drugs. Women may require a smaller dose of some drugs than men. This is because many women are smaller and have a different body fat-to-water ratio than men.

Disease

The presence of disease may influence the action of some drugs. Sometimes disease is an indication for not prescribing a drug or for reducing the dose of a certain drug. Both hepatic (liver) and renal (kidney) diseases can greatly affect drug response.

In liver disease, for example, the ability to metabolize or detoxify a specific type of drug may be impaired. If the average or normal dose of the drug is given, the liver may be unable to metabolize the drug at a normal rate. Consequently, the drug may be excreted from the body at a much slower rate than normal. The primary health care provider may then decide to prescribe a lower dose and lengthen the time between doses because liver function is abnormal.

Clients with kidney disease may exhibit drug toxicity and a longer duration of drug action. The dosage of drugs may be reduced to prevent the accumulation of toxic levels in the blood or further injury to the kidney.

Route of Administration

The method used to get the drug into a person’s body will affect the drug response. IV administration of a drug produces the most rapid drug action because the GI tract is completely bypassed. Next in order of time of action is the intramuscular (IM) route, followed by the subcutaneous (Subcut) route. Giving a drug orally usually produces the slowest drug action.

Some drugs can be given only by one route; for example, antacids are only given orally. Other drugs are available in oral and parenteral (IV, IM, Subcut) forms. The primary health care provider selects the route of administration based on many factors, including the desired rate of action. For example, the client with a severe cardiac problem may require IV administration of a drug that affects the heart. Another client with a mild cardiac problem may experience a good response to oral administration of the same drug.

NURSING IMPLICATIONS WITH DRUG ACTIONS

Many factors can influence drug action. Consult appropriate references or the clinical pharmacist if there is any question about the dosage of a drug, whether other drugs the client is receiving will interfere with the drug being given, or whether the oral drug should or should not be given with food.

Drug reactions are potentially serious. Observe all clients for adverse drug reactions, drug idiosyncrasy, and evidence of drug tolerance (when applicable). It is important to report all drug reactions or any unusual drug effect to the primary health care provider.

Use good judgment when reporting adverse drug reactions to the primary health care provider. Accurate observation and evaluation of the circumstances are essential; record all observations in the client’s record. If there is any question regarding the events that are occurring, withhold the drug and immediately contact the primary health care provider.

HERBAL MEDICINE AND HEALTH CARE

Herbal medicine, herbalism, and herbal therapy are all names used for complementary/alternative therapies that use plants or herbs to treat various disorders. Individuals worldwide use herbal therapy and dietary supplements extensively. According to the World Health Organization, 80% of the world’s population relies on herbs for a substantial part of their health care. Herbs have been used by virtually every culture in the world throughout history. For example, Hippocrates prescribed St. John’s wort, currently a popular herbal remedy for depression. Native Americans use plants such as coneflower, ginseng, and ginger for therapeutic purposes. Herbal therapy is part of the group of nontraditional therapies commonly known as complementary and alternative medicine (CAM).

Complementary and Alternative Medicine

The National Center for Complementary and Integrative Health (NCCIH) is one of the 27 institutes and centers that make up the National Institutes of Health. The NCCIH explores complementary and alternative (or also called integrative) healing practices through scientific research. It also trains CAM scientists and disseminates the information gleaned from the research it conducts. Among the various purposes of the NCCIH is to evaluate the safety and efficacy of widely used natural products, such as herbal remedies and dietary and food supplements. The NCCIH is dedicated to developing programs and encouraging scientists to investigate CAM treatments that show promise. The NCCIH budget has steadily grown, reflecting the public’s interest and need for CAM information that is based on rigorous scientific research.

The NCCIH defines CAM as a “group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.” Examples of complementary therapies are relaxation techniques, massage, aromatherapy, and healing touch. Complementary therapies are often used with traditional health care to “complement” conventional medicine. Alternative therapies, on the other hand, are therapies used in place of or instead of conventional or Western medicine. The term complementary/alternative therapy often is used as an umbrella term for many therapies from all over the world.

Dietary Supplement Health and Education Act

In addition to vitamins and minerals, herbs are classified as dietary or nutritional supplements. Nutritional or dietary substances are terms used by the federal government to identify substances that are not regulated by the FDA but are purported to be effective in promoting health. Herbs are not sold and promoted in the United States as drugs. Therefore, they do not have to meet the same standards as drug and OTC medications for proof of safety and effectiveness and what the FDA calls “good manufacturing practices.”

Because natural products cannot be patented in the United States, it is not profitable for drug manufacturers to spend the millions of dollars and the 7–12 years needed to study and develop these products as drugs. In 1994, the US government passed the Dietary Supplement Health and Education Act (DSHEA). This act defines substances such as herbs, vitamins, minerals, amino acids, and other natural substances as “dietary supplements.” The act permits general health claims such as “improves memory” or “promotes regularity” as long as the label also has a disclaimer stating that the supplements are not approved by the FDA and are not intended to diagnose, treat, cure, or prevent any disease (Fig. 1.4). The claims must be truthful and not misleading and supported by scientific evidence. Some manufacturers have abused the law by making exaggerated claims, but the FDA has the power to enforce the law, which it has done, and these claims have decreased.

The use of herbs and dietary supplements to treat various disorders is common. At least 76% of the adult population in the United States use dietary supplements on a daily basis (CRN Survey, 2017). Herbs are used for various effects, such as boosting the immune system, treating depression, and promoting relaxation. Individuals are becoming more aware of the benefits of herbal therapies and dietary supplements. Advertisements, books, magazines, and Internet sites concerning these topics are prolific. People eager to cure or control various disorders take herbs, teas, megadoses of vitamins, and various other natural products. Although much information is available on dietary supplements and herbal therapy, obtaining the correct information can be difficult at times. Medicinal herbs and dietary substances are available at supermarkets, pharmacies, health food stores, and specialty herb stores and through the Internet. The potential for misinformation abounds.

Because these substances are “natural products,” many individuals incorrectly assume that they are without adverse effects. When any herbal remedy or dietary supplement is used, it should be reported to the nurse and the primary health care provider. Many of these natural substances have strong pharmacologic activity, and some may interact with prescription drugs or be toxic in the body. For example, comfrey, an herb that was once widely used to promote digestion, can cause liver damage. Although it may still be available in some areas, it is a dangerous herb and is not recommended for use as a supplement.

When obtaining the drug history, always question the client about the use of herbs, teas, vitamins, or other dietary supplements. Many clients consider herbs as natural and therefore safe. Some also neglect to report the use of an herbal tea as part of the health care regimen because they do not think of it as such. Explain to the client that just because an herbal supplement is labeled “natural,” it does not mean the supplement is safe or without harmful effects. Herbal supplements can act the same way as drugs and can cause medical problems if not used correctly or if taken in large amounts. Box 1.2 identifies teaching points to consider when discussing the use of herbs and dietary supplements with clients.

BOX 1.2 Teaching Points When Discussing Herbal Therapy

Herbal preparations are not necessarily safe just because they are natural. Unlike prescription and OTC medicines, herbal products and supplements do not have to be tested to prove they work well and are safe before they are sold. Also, they may not be pure. They might contain other ingredients, such as plant pollen, that could make you sick. Sometimes they contain drugs that are not listed on the label, such as steroids or estrogens.

If you have health problems, there may be an increased danger in taking herbal preparations. These conditions include blood-clotting problems, cancer, diabetes, an enlarged prostate gland, epilepsy, glaucoma, heart disease, high blood pressure, immune system problems, psychiatric problems, Parkinson disease, liver problems, stroke, and thyroid problems.

If you are going to have surgery, be sure to tell your doctor if you use herbal products. Herbal products can cause problems with surgery, including bleeding and problems with anesthesia. Stop using herbal products at least 2 weeks before surgery, or sooner if your doctor recommends it.

Herbal products can change the way prescription and OTC drugs work. Herbal health products or supplements can affect the way the body processes drugs. When this happens, your medicine may not work the way it should. This may mean the drugs are not absorbed at high-enough levels to help the conditions for which they are prescribed. This can cause serious problems. You should be especially cautious about using herbal health products or supplements if you take a drug in one of the following categories.

 If you take any of these drugs, talk to your doctor before taking any type of herbal product or supplement.

Drugs to treat depression, anxiety, or other psychiatric problems

Antiseizure drugs

Blood thinners

Blood pressure medicine

Heart medicine

Drugs to treat diabetes

Cancer drugs

Herbal products can cause other problems, too. You should not take more than the recommended dose of any herbal health product or supplement. The problems that these products can cause are much more likely to occur if you take too much or take them for too long.

Because herbal supplements are not regulated by the FDA, products lack standardization with regard to purity and potency. In addition, multiple ingredients in products and batch-to-batch variation make it difficult to determine if reactions occur as a result of the herb itself. To assist with the identification of herb–drug interactions, report any potential interactions to the FDA through its MedWatch program (see Box 1.1). It is especially important to take special care when clients are taking any drugs with a narrow therapeutic index (the difference between the minimum therapeutic and minimum toxic drug concentrations is small—such as warfarin, a blood thinner) and herbal supplements. Because the absorption, metabolism, distribution, and elimination characteristics of most herbal products are poorly understood, much of the information on herb–drug interactions is speculative. Herb–drug interactions are sporadically reported and difficult to determine.

Although a complete discussion about the use of herbs is beyond the scope of this book, it is important to remember that the use of herbs and dietary supplements is commonplace in many areas of the country. To help you become more aware of herbal therapy and dietary supplements, Appendix D gives an overview of selected common herbs and dietary supplements featured in select chapters. In addition, “alerts” related to herbs and dietary supplements appear throughout this text to alert the learner to valuable information and precautions.