Understanding Pharmacology for Health Professionals

Unit One THE PAST HISTORY, PRESENT USES, AND FUTURE OF DRUGS Chapter 1 Introduction to Pharmacology and the History of Drugs Chapter 2 Drug Design, Testing, Manufacturing, and Marketing Chapter 3 Drug Forms Chapter 4 Routes of Administration and the Drug Cycle Chapter 5 Using Drugs Therapeutically

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Chapter 6 The Prescription

Understanding Pharmacology for Health Professionals, Fourth Edition, by Susan M. Turley, MA (Educ), BSN, RN, RHIT, CMT. Published by Prentice Hall. Copyright © 2010 by Pearson Education, Inc.

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Introduction to Pharmacology and the History of Drugs CHAPTER CONTENTS Origins of Pharmacology Words Medical Uses for Drugs Drugs in Ancient Times Modern Drugs Derived from Natural Sources Drugs in the 1800s and 1900s Pharmaceutical Timeline Mislabeled and Dangerous Drugs

Drug Legislation and Drug Agencies Prescription and Over-the-Counter Drugs Schedule Drugs Orphan Drugs Quiz Yourself Clinical Applications Multimedia Extension Exercises

Learning Objectives After you study this chapter, you should be able to 1. Describe the origin of the words pharmacology, drug, medicine, and other words related to specialty fields within pharmacology. 2. Describe the three general medical uses for drugs. 3. Give the origin and meaning of the symbol Rx. 4. Name at least five drugs historically derived from plant, animal, or mineral sources that are still in use today. 5. Describe the process of the preparation of drugs in the 1800s to early 1900s. 6. Name 10 major pharmaceutical milestones that have occurred since the 1800s. 7. Describe the use of mislabeled and dangerous drugs and the problem they presented in the past for consumer safety. 8. Describe the origin and content of the various drug laws.

10. Differentiate between prescription and over-the-counter (OTC) drugs. 11. Define schedule drugs and describe the five categories of controlled substances. 12. Define orphan drugs.


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9. Describe the function of the Food and Drug Administration (FDA) with respect to approving or removing drugs from the market.

CHAPTER 1 • INTRODUCTION TO PHARMACOLOGY AND THE HISTORY OF DRUGS

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harmacology is a fascinating and multifaceted discipline that impacts not only our chosen career in health care, but also our personal lives. From our role as members of the healthcare team to that of consumers, pharmacology plays a part in our lives. The study of pharmacology covers a broad spectrum of diverse, yet interrelated, topics: botany, molecular chemistry, research, toxicology, legislation, and patient education. There is an excitement inherent in the study of pharmacology. The field of pharmacology is amazing in its scope, ranging from the historical and present day uses of herbs and plant extracts to day-to-day painstaking research that produces unusable products as well as life-saving drugs to the future with genetic manipulation, molecular pharmacology, adult stem cell therapy, and a seemingly limitless potential for discovery.

Origins of Pharmacology Words Pharmacology Pharmacology is the study of drugs and their interactions with living organisms. The word pharmacology comes from the Greek word pharmakon, which means medicine or drug, and the suffix -logy, which means the study of. Pharmacology is concerned with the nature of drugs, their effects in the body, drug doses, side effects, and so forth. Pharmacology is a general word. Other more specific words related to specialty fields within the field of pharmacology include the following: molecular pharmacology the study of the chemical structures of drugs and the effects of drugs at the molecular level within cells pharmacodynamics the mechanisms of action by which drugs produce their effects (desired or undesired) based on time and dose pharmacogenetics how the genetic makeup of different people affects their responses to certain drugs pharmacogenomics using genome technology to discover new drugs pharmacokinetics how drugs move through the body in the processes of absorption, distribution, metabolism, and excretion pharmacotherapy using drugs to affect the body therapeutically.

Drugs and Medicines

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The word drug is derived from the Dutch word droog, which means dry, and refers to the use of dried herbs and plants as the first medicines. The Latin word for drug is medicina, from which we derive the words medicine and medication. A drug or a medicine can be thought of as any nonfood chemical substance that affects the mind or the body. The word medicine refers to a drug that is deliberately administered for its medicinal value as a preventive, diagnostic, or therapeutic agent (see ■ FIGURE 1–1). The word drug can be used interchangeably with the word medicine, but drug can also refer specifically to chemical substances that do not have a preventive, diagnostic, or therapeutic use (e.g., illicit or street drugs).

Medical Uses for Drugs Drugs have three medical uses. They are used to prevent disease, to diagnose disease, and to treat symptoms, signs, conditions, and diseases. The study of these uses is known as pharmacotherapy.


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UNIT ONE • THE PAST HISTORY, PRESENT USES, AND FUTURE OF DRUGS

■ FIGURE 1–1 Medications. Medications or medicines are drugs that are used to prevent, diagnose, or treat symptoms, signs, conditions, and diseases.

1. Preventive use. Drugs are used to prevent the occurrence of diseases or conditions. The administration of a preventive drug is known as prophylaxis. Prophylaxis is from a Greek word meaning to keep guard before. Examples of the preventive uses of drugs include the following: ■ Drugs taken prior to traveling to prevent motion sickness (see ■ FIGURE 1–2 ) ■ Contraceptive drugs taken to prevent pregnancy ■ Vaccinations given to immunize children or adults against certain diseases, such as polio, diphtheria, or influenza. 2. Diagnostic use. Drugs are used by themselves or in conjunction with radiologic procedures and other types of medical tests to provide evidence of a disease process. Examples of the diagnostic uses of drugs include the following: ■ Radiopaque contrast dyes used during x-ray procedures ■ Drugs that mimic the cardiac effect of exercise in patients who cannot undergo regular cardiac exercise stress testing.


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■ FIGURE 1–2 Preventive use of drugs. Dramamine is an over-the-counter drug that is taken to prevent motion sickness and vomiting. The word vomiting does not appear on the drug package, but the word antiemetic, which means pertaining to against vomiting, appears at the top right.


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Clinical Applications The American Academy of Pediatrics issues an annual immunization schedule for preventing childhood diseases. All children must receive certain immunizations before they are permitted to enroll in school. Exceptions are granted for religious reasons or when immunizations are medically inadvisable.

3. Therapeutic use. The majority of drugs are used to control, improve, or cure symptoms, signs, conditions, or diseases of a physiologic or psychological nature. Examples of the therapeutic uses of drugs include the following: ■ Antibiotic drugs to kill bacteria and cure an infection ■ Analgesic drugs to control the pain and inflammation of arthritis ■ Insulin to treat diabetes mellitus.

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Drugs in Ancient Times Pharmacology is one of the oldest branches of medicine. Ancient peoples such as the Sumerians and Egyptians recorded the use of drugs on clay tablets, on wall paintings in tombs, and on papyrus as early as 2000 B.C. The Egyptians treated diseases with substances such as frogs’ bile, sour milk, lizards’ blood, pigs’ teeth, sugar cakes, dirt, spiders’ webs, hippopotamus’ oil, and toads’ eyelids. The Egyptians applied moldy bread to abrasions, a practice that actually had some therapeutic basis as, many centuries later, penicillin was extracted from a mold. An Egyptian medicinal scroll, the Ebers Papyrus from 1500 B.C. (discovered in the early 1800s), contained the names of 800 different herbal formulations and prescriptions. The Egyptians also extracted the oil from various plants known for their healing properties. In 1922 when King Tutankhamun’s tomb was opened, archeologists discovered 350 alabaster jars of plant oils in it. The ancient Chinese practiced healing arts that emphasized the use of herbs and some minerals, but few animal products (see ■ FIGURE 1–3). Herbal preparations were used in conjunction with acupuncture, massage, and exercise. Shen Nong completed the first Chinese book on herbal medicine in 3494 B.C. It included 365 different herbal remedies.


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■ FIGURE 1–3 Chinese herbal medicines. This Chinese pharmacist prepares herbal medicines in much the same way that his ancestors did, by using dried herbs which are then crushed into powder. He is making four batches of the same medicine, each of which contains the same mixture of herbs. The wall behind him holds drawers of many different types of dried herbs. In 1970, the Chinese Academy of Medical Science compiled a collection of traditional herbal remedies. American pharmacists evaluated those remedies and found that 45 percent of them were therapeutic, according to Western standards of medicine.

Many other cultures around the world furthered the use of drugs within their own cultures, including the Native Americans of North America. The Aztec Indians of Mexico grew many herbs with medicinal properties. Aztec King Montezuma maintained royal gardens of medicinal plants. The Greeks and Romans furthered the study of medicine through an understanding of anatomy and physiology, which was an important first step toward understanding how drugs exert their effects in the body. Ancient drugs were prepared according to standard recipes that involved drying, crushing, and combining a variety of plants, substances from animals, or minerals. The symbol Rx, which comes from the Latin word recipe, meaning take, indicates a prescription, the combining of ingredients to form a drug. The use of some ingredients was based on medical lore and superstition. Some ingredients had therapeutic value, but others were worthless or actually harmful. Medieval physicians prescribed a broad range of drugs from herbs to metals (e.g., powdered gold) to addictive substances (e.g., opium). In the 1600s, patients were advised to eat soap to cure blood in the urine and put mercury in beer to cure intestinal worms. Because little was known about even the most fundamental physical and chemical processes of the body, the therapeutic use of drugs was not an exact science.

Modern Drugs Derived from Natural Sources Amazingly, there are a number of drugs, based on old prescriptions, that are still in use today. These include drugs derived from plants, animals, and minerals.

Drugs Derived from Plants


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The medicinal use of the foxglove plant was noted in 13th-century writings (see ■ FIGURE 1–4). A derivative of this plant is used to make the drug digoxin (Lanoxin), which is still used today to treat congestive heart failure.


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■ FIGURE 1–4 Foxglove plant. This beautiful wild flowering plant is commonly known as foxglove, but its scientific name is Digitalis lanata. The drug digitalis (which is no longer in use) came from this plant, as does the modern drug digoxin (Lanoxin), which is used to treat congestive heart failure.

The belladonna plant was the original source of two drugs that are still in use today—atropine and scopolamine. Belladonna means beautiful lady in Italian. “Sixteenth century Italian women ... squeezed the juice of the berries of these plants into their eyes to widen and brighten them.” (Michael C. Gerald, Pharmacology: An Introduction to Drugs, 2nd ed. Englewood Cliffs, NJ: Prentice Hall, 1981, p. 149, out of print.) Atropine is still used to dilate the pupil in patients with inflammatory conditions of the iris. Scopolamine is used to treat motion sickness. The opium poppy has been used for centuries as a painkiller and also as a recreational drug to induce euphoria and a trance-like state. The sap from the seedheads of the poppy flower Papaver somniferum contain opium, a substance that is the source of the illegal street drug heroin, which has no medical use, as well as the prescription drug morphine, which is a potent analgesic drug used to treat severe pain. Colchicine, a drug still used to treat gout, was used for that same purpose in the sixth century. It was originally derived from the autumn crocus known as Colchicum autumnale. Ephedrine is present in the leaves of a bushy shrub (species name, Ephedra). The leaves were burned and used by the ancient Chinese to treat respiratory ailments. Today, ephedrine is present in over-the-counter bronchodilator drugs.

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Did You Know? Herbs have been a part of all cultures for centuries and have been mentioned frequently in literature. Henbane, a very toxic herb, was supposed to have been the poison that Claudius used to kill his brother, Hamlet’s father. ”Henbane should not be confused with wolfsbane. Students of literature know wolfsbane to be useful as a vampire repellant (Dracula, 1897); however, we should point out that double-blind studies demonstrating the effectiveness of this plant have not as yet been conducted.” (Michael C. Gerald, Pharmacology: An Introduction to Drugs, 2nd ed. Englewood Cliffs, NJ: Prentice Hall, 1981, p. 149, out of print.)


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Some estrogen hormone replacement therapy drugs are derived from yams. The drug galantamine (Razadyne), which is used to treat Alzheimer’s disease, is derived from daffodil bulbs. In addition, many of the gums, oils, and bases in which drugs are dissolved come from plant sources. Many drugs contain soybean oil, sesame seed oil, or olive oil. Other plants have also become the sources of some modern drugs (see ■ TABLE 1–1). ■ TABLE 1–1 Other plant sources of some modern drugs Plant Sources

Modern Drug

black cohosh

Remifemin (used to treat menopause hot flashes)

cinchona bark

quinine (used to treat malaria)

cocoa butter

binder or filler ingredient

hot pepper plant

capsaicin (topical pain relief)

mold

penicillin (antibiotic drug) statin drugs (used to treat high cholesterol)

periwinkle (vinca)

vincristine (used to treat cancer)

rose hips

vitamin C (see ■ FIGURE 1–5)

snakeroot

reserpine (used to treat hypertension)

willow bark

aspirin (used to treat pain)

■ FIGURE 1–5 Rose hips. Hips are the botanical name for the rounded fruit of a rose. Powdered rose hips are still the source of natural vitamin C in some over-the-counter vitamin C dietary supplements. Other products use synthetic vitamin C.

000200010270643129 Understanding Pharmacology for Health Professionals, Fourth Edition, by Susan M. Turley, MA (Educ), BSN, RN, RHIT, CMT. Published by Prentice Hall. Copyright © 2010 by Pearson Education, Inc.


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Drugs Derived from Animals Thyroid supplement drugs are composed of dried (desiccated) thyroid gland tissue taken from animals. Thyroid supplement drugs are used to treat patients with hypothyroidism. The drug Premarin, a female hormone replacement drug used to relieve the symptoms of menopause, is derived from pregnant mares’ urine, and the trade name is formed from selected letters taken from that phrase. Lanolin, a common ingredient of topical skin drugs, is obtained from the purified fat of processed sheeps’ wool. In the past, the only source of insulin used to treat diabetes mellitus was from ground-up animal pancreas (see ■ FIGURE 1–6). This type of insulin is still available.

■ FIGURE 1–6 NPH Iletin II insulin. The drug label clearly shows that the source of this insulin is from pork (in vertical capital letters).

Drugs Derived from Minerals Minerals, such as calcium and iron, are available as individual dietary supplements, and trace minerals, such as copper, magnesium, selenium, and zinc, are included in many multivitamin supplements. Centrum multivitamins use the advertising slogan “From A to Zinc,” to show that they contain vitamins and minerals alphabetically from vitamin A through zinc. Potassium, in the form of potassium chloride, is given in conjunction with diuretic drugs because diuretic drugs cause increased excretion of potassium (and water). The cardiac drug quinapril (Accupril) contains red iron oxide as an inert ingredient in its brown tablets.

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Drugs in the 1800s and 1900s It was not until the 1800s that chemists developed techniques to extract and isolate pure substances from crude drug preparations. The isolation of morphine in 1803 by a German pharmacist marked the beginning of modern drug therapy using chemically pure ingredients. In the early 1900s, the extraction and preparation of drugs was still a time-consuming process that utilized test tubes, filters, and Bunsen burners. Pharmacists at that time actually prepared the drugs they dispensed. Daily, they made milk of magnesia, paregoric, and syrup bases for liquid medicines. In addition, they hand-rolled cocoa butter suppositories. They measured out drugs in minims, drams, ounces, grains, and scruples (the apothecary system of measurement). Much has changed since then. Many drugs are now completely synthetic rather than derived from natural sources. Other natural drugs have undergone chemical modification and molecular restructuring to create new drugs that possess superior pharmacologic action. In addition, the pharmacist no longer prepares drugs, but dispenses them and provides patient information and education.


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Pharmaceutical Timeline The following list briefly notes some major pharmaceutical milestones dating from the 1800s to the present time (see ■ TABLE 1–2).

■ TABLE 1–2 Major pharmaceutical milestones of the 1800s to the present Year

1803 1827 1843

Major Pharmaceutical Milestone

Morphine isolated from crude opium Merck & Company, a German drug company, begins the first commercial production of morphine Dr. Alexander Wood of Scotland creates the syringe and injects patients with morphine

1899

Aspirin introduced

1908

Sulfanilamide introduced (first anti-infective drug)

1912

Phenobarbital introduced for epilepsy (first antiepileptic drug)

1913

Vitamins A and B discovered

1922

Insulin introduced (first drug for diabetes mellitus)

1938

Dilantin introduced for epilepsy

1941

Penicillin introduced (first antibiotic drug)

1945

Benadryl introduced (first antihistamine drug)

1948

Cortisone introduced (first corticosteroid drug)

1952

Thorazine introduced for psychosis (first antipsychotic drug)

1952

Hydrocortisone introduced (first topical corticosteroid drug)

1957

Librium introduced for neurosis (first antianxiety drug)

1958

Haldol introduced for psychosis

1966

Clotting factors introduced for hemophilia

1967

Inderal introduced for hypertension (first beta-blocker drug)

1970

Levodopa introduced for Parkinson’s disease

1972

Researchers discover a receptor in the brain that responds to drugs derived from opium

1977

Tagamet introduced for peptic ulcers (first H2 blocker drug)

1978

First portable insulin pump introduced

1981

Verapamil introduced for heart arrhythmia (first calcium channel blocker drug)

1982

Humulin (human insulin) introduced (first drug made by recombinant DNA technology) (continued) 000200010270643129



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■ TABLE 1–2 Major (continued) pharmaceutical milestones of the 1800s to the present Year

Major Pharmaceutical Milestone

Topical prescription drug hydrocortisone approved for over-the-counter sales

1985

ACE inhibitor drugs introduced for hypertension

1986

Orthoclone OKT3 introduced (first monoclonal antibody drug)

1987

Mevacor introduced (first statin drug for high cholesterol)

1987

Alteplase (Activase) introduced for dissolving blood clots (first tissue plasminogen activator drug)

1987

AZT (zidovudine, Retrovir) introduced (first drug for HIV)

1992

Proscar introduced for benign prostatic hypertrophy (first nonsurgical treatment)

1993

Cognex introduced (first drug for Alzheimer’s disease)

1994

Combination drug therapy introduced for peptic ulcers caused by Helicobacter pylori

1995

Cozaar introduced for hypertension (first angiotensin II receptor blocker drug)

1996

Invirase introduced for HIV (first protease inhibitor drug)

1996

Fosamax introduced for osteoporosis (first nonhormonal drug treatment)

1996

Nicoderm introduced (first prescription-strength, over-the-counter drug for stopping smoking)

1997

Plavix introduced for the treatment of acute coronary syndrome

1998

Viagra introduced (first oral drug for erectile dysfunction in men)

1999

Celebrex introduced for arthritis (first COX-2 inhibitor drug)

2000

Deciphering of the human genome opens the field of gene therapy in pharmacology

2001

Anthrax attack on the United States creates high demand for the antibiotic drugs ciprofloxin and doxycycline

2002

Botox introduced for the treatment of facial wrinkles

2003

Fuzeon introduced (first fusion inhibitor drug for HIV)

2004

Lunesta introduced for the long-term treatment of chronic insomnia

2005

Requip introduced (first drug for restless legs syndrome)

2006

Gardasil introduced (first vaccine against cervical cancer caused by HPV)

2007

Exelon introduced (first transdermal drug patch for Alzheimer’s disease)

2007

Zyrtek is the first drug to have the same dose strength for both its prescription and over-the-counter forms

2007

Isentress introduced (first integrase inhibitor drug for HIV)

2008

Xenazine introduced (first FDA-approved drug for Huntington’s disease)

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1983


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Mislabeled and Dangerous Drugs From the early history of pharmacology, most physicians attempted to treat patients based on what little scientific knowledge was available to them. As early as 2100 B.C., the Code of Hammurabi gave severe penalties for malpractice. However, throughout medical history many ineffective, mislabeled, and even dangerous drugs have been manufactured, advertised, and prescribed. In 1680, English apothecary (pharmacist) Thomas Sydenham created the drug Sydenham’s Laudanum, which contained powdered opium, wine, and herbs. During the 1700s and 1800s, drugs with names such as Warner’s Safe Cure for Diabetes, Dr. Shreve’s Anti-Gallstone Remedy, and Anti-Morbific Great Liver and Kidney Medicine were commonly sold without regulation and were accompanied by extravagant claims of cures. Drugs often contained one of the addicting ingredients of opium, morphine, or cocaine without its presence being listed on the label. Ayer’s Cherry Pectoral, advertised for respiratory ailments, contained cherry flavoring and heroin. Even when a drug included the name of the addictive ingredient in its title or on its label (see ■ FIGURE 1–7), consumers were often not aware of its addictive qualities. One drug prescribed for respiratory ailments, hydrocyanic acid, caused many deaths. (This poison, which as a gas contains cyanide, is used for legal executions.)

■ FIGURE 1–7 Cocaine in a common drug. This 1885 advertisement was for the drug Cocaine Toothache Drops. It was not known at that time that cocaine was a highly addictive drug. Children as well as adults became addicted to this drug.

It is estimated that in the early 1900s one out of every 200 Americans was addicted, most of them middle-class women who used these drugs for themselves and their children. Consumer warnings against the misuse of drugs, the possibility of addiction, or dangerous drug side effects did not exist. At that time, the prevailing dictum was “Let the buyer beware.”

Drug Legislation and Drug Agencies


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Laws were passed in the 1900s to protect the public from unscrupulous drug sellers, as well as from worthless, mislabeled, and dangerous drugs that were then on the market. The drug manufacturers strongly opposed drug laws, but public outrage resulted in the passage of The Food and Drugs Act of 1906, the first federal drug law. A 1912 amendment to this act required the accurate labeling of drugs to prevent substitution or mislabeling of ingredients. It also stated that only drugs listed in the


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United States Pharmacopeia or National Formulary could be prescribed. Nevertheless, many worthless drugs remained on the market because the burden of proof lay with the government to show fraud on the part of the seller. It took a national tragedy to force a much-needed update of The Food and Drugs Act of 1906. Sulfonamide, an early anti-infective drug, was widely used in the United States in 1937. After an extensive advertising campaign aimed at physicians, a Tennessee company marketed this drug in a raspberry-flavored base and called it “Elixir of Sulfonamide.” This base had been tested by the manufacturer for flavor and fragrance but not for safety. Elixirs are made from a sweetened alcohol base, but this drug base was an industrial-strength liquid solvent. A number of children died after taking less than one ounce of this drug, and over 350 individuals were poisoned. At that time, a drug manufacturer did not need FDA approval before marketing a drug. Because of this tragedy, Congress passed The Food, Drug, and Cosmetic Act of 1938 that previously had lacked the support it needed to pass. As a result, the government no longer needed proof of fraud to stop the sale of a drug. It could seize any drug suspected of being toxic. Secondly, the burden of proof was shifted to the drug manufacturers, who were required to provide data based on scientific experiments to show that their product was safe before they were allowed to market it. It became the job of the Food and Drug Administration (FDA) to review these data and evaluate the safety of drugs. In 1951, the Durham-Humphrey Amendment to The Food, Drug, and Cosmetic Act defined prescription drugs as those drugs that could only be given to patients under the care of a physician. In the late 1950s, the drug thalidomide was developed in West Germany and was used extensively during early pregnancy to treat morning sickness in women. The FDA refused to approve its use in the United States without further studies. Before these additional studies could be completed by the manufacturer, evidence against the safety of the drug began to accumulate. Over 8,000 babies in Europe were born with deformed limbs (“seal limbs,” or phocomelia). This tragedy resulted in the passage of the 1962 Kefauver-Harris Amendment to The Food, Drug, and Cosmetic Act, which tightened control on existing prescription drugs and new drugs. It required that drugs be shown to be both safe and effective before being marketed. It also required manufacturers to report adverse side effects from new drugs. Since that time, many drugs have been kept from the market or have been removed from the market because of a lack of safety.

Historical Notes

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Because of its devastating adverse effects in unborn children, thalidomide would have been relegated to an obscure footnote in medical history, but in 1997 it was discovered to be a useful drug in treating cancer, AIDS, and leprosy. The potential adverse effects of this drug are so great that it is only considered as a viable treatment option for these life-threatening diseases. The FDA regulates the use of thalidomide in two ways: (1) by limiting the number of physicians who can prescribe it and (2) by requiring women taking the drug not to have sexual intercourse or to use two forms of birth control (so that there is virtually no risk of them giving birth to a child with phocomelia). Thalidomide is now an official prescription drug used to treat multiple myeloma, leprosy, graft-versus-host disease, and several types of cancers. It is also officially recognized as an orphan drug that is used to treat wasting syndrome from HIV, as well as Crohn’s disease.

For each new drug, the FDA must weigh the inherent risks of the drug against its potential benefits. To do this thoroughly, the FDA must take the time to complete its review process before it issues a final approval (or rejection) of a new drug. In 1988, the Food and Drug Administration was moved under the federal Department of Health and Human Services.


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■ FIGURE 1–8 Dietary supplements. Dietary supplements, such as vitamins, minerals, and herbs, are manufactured in tablets and capsules that resemble prescription and over-the-counter drugs. However, the bottle label clearly states “Dietary Supplement,” and the reverse side of the bottle provides information under the heading of “Supplement Facts.”


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In 1994, the Dietary Supplements and Health and Education Act was passed. This legislation allowed the FDA to set up guidelines for the manufacturers of herbal products and dietary supplements (see ■ FIGURE 1–8). Although the FDA could not regulate these products and the products were still available without a prescription, the drug manufacturers were now liable for any claims against their products in accordance with the FDA guidelines. In the early 1990s, FDA approval of a new drug took an average of 34 months. However, for certain critical drugs the process could be much shorter. The first drug effective against HIV was approved by the FDA in 1987 in just 107 days. Despite the rapid handling of many critical drugs, critics still pointed to a time lag in the approval of other new drugs. They argued that some drugs were available in other countries for quite some time before they received approval by the FDA for use in the United States. For example, Inderal, a widely used drug for hypertension and arrhythmias, was available in Europe for nearly 10 years before it was finally approved for use in the United States in 1967. In response to this criticism, the FDA made a concerted effort to streamline the approval process, particularly with respect to drugs used to treat life-threatening diseases. In 1996, indinavir (Crixivan), a protease inhibitor drug used to treat HIV, was approved by the FDA in record time, just 42 days after the new drug application was submitted. In 1997, then-President Clinton signed the Food and Drug Administration (FDA) Modernization Act. It gave the FDA the authority to accelerate the approval process for certain types of drugs. By 2000, the average review time for new drugs had fallen to less than 15 months. Critically needed drugs (as well as those for whom the drug manufacturer pays a special fee) can be approved in as little as 6 months. In addition, the FDA allows physicians to prescribe some investigational drugs even before they are officially approved for marketing. These drugs are for life-threatening diseases for which no other alternative therapy exists. In order to prescribe such a drug, the FDA requires an Emergency Treatment Investigational New Drug (IND) application to be filed. This is also known as a Compassionate Use IND application. In the 1970s, long before the cardiac drug amiodarone (Cordarone) was on the market (final approval, 1985), cardiologists prescribed it as an investigational new drug to treat patients with life-threatening cardiac arrhythmias that did not respond to other antiarrhythmic drugs. Similarly, the first drug for HIV was prescribed for patients before its approval in 1987. This was done under a Compassionate Use IND application. Under the federal regulations of HIPAA (pronounced “hip-ah”), the Health Insurance Portability and Accountability Act of 1996, all healthcare settings must provide patients with a statement that verifies that their health record information, including all drug information, is kept


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secure and is only released to authorized inquiries from other healthcare providers, insurance companies, or healthcare quality monitoring organizations.

Prescription and Over-the-Counter Drugs The Food and Drug Administration (FDA) regulates prescription drugs and over-the-counter drugs. Prescription drugs are defined as those drugs that are not safe to use except under professional medical supervision. Prescription drugs can only be obtained with a written prescription or verbal order from a physician, dentist, nurse practitioner, or other healthcare provider whose license permits this. Prescription drugs are also known as legend drugs because the drug manufacturer and pharmacist add one of these two legends (inscriptions) to the drug package and to the filled prescription bottle: “Caution: Federal law prohibits dispensing without a prescription” or “Rx only.” In addition to prescription drugs, the FDA also regulates over-the-counter (OTC) drugs. An OTC drug is defined as one that can be purchased without a prescription and is generally considered safe for consumers to use if the label’s directions and warnings are followed carefully. OTC drugs comprise more than half of all the drugs used in the United States. For many years, there was a clear distinction between prescription drugs and OTC drugs. Then, in 1983, the topical prescription drug hydrocortisone was approved for over-the-counter sales and many other drugs followed. The OTC drug is the same as the original prescription drug, but the recommended dose is usually just a fraction (often half) of the dose of the prescription drug. An exception to this is cetirizine (Zyrtec), a prescription antihistamine drug whose over-the-counter dose, as approved by the FDA, is the same as its prescription dose. In 1992, the OTC Drugs Advisory Committee was created to assist the FDA in reviewing drugs and determining which ones were safe and appropriate for over-the-counter use (see ■ TABLE 1–3).

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■ TABLE 1–3 Some prescription drugs that are also OTC drugs

Generic Name

Prescription Trade Name

OTC Trade Name

Therapeutic Use

butenafine

Mentax

Lotrimin Ultra

skin fungal infection

butoconazole

Gynazole-1

Mycelex-3

vaginal yeast infection

cetirizine

Zyrtec

Zyrtec

nasal allergies

cimetidine

Tagamet

Tagamet HB 200

heartburn/ulcer

cromolyn

Intal

Nasalcrom

nasal allergies

famotidine

Pepcid

Pepcid AC

heartburn/ulcer

hydrocortisone

Hycort

Cortizone-5

skin inflammation

ibuprofen

Motrin

Advil, Motrin IB

pain

naproxen

Naprosyn

Aleve

pain

nicotine

Nicotrol Inhaler

Nicoderm CQ

quit smoking

nizatidine

Axid

Axid AR

heartburn/ulcer

omeprazole

Prilosec

Prilosec OTC

heartburn/ulcer

ranitidine

Zantac

Zantac 75

heartburn/ulcer


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This committee consists of physicians and pharmacists, as well as one nonvoting member from the drug/cosmetics industry. The FDA approves a prescription drug being reclassified as an OTC drug if the following criteria are met: (1) the indication for the drug’s OTC use is similar to its use as a prescription drug, (2) the patient can easily diagnose and monitor his or her own condition when using the OTC drug, (3) the OTC drug has a low rate of side effects/toxicity and a low potential for abuse, and (4) use of the OTC drug does not require the patient to have any special monitoring or testing.

Focus on Healthcare Issues Supporters of the reclassification of some prescription drugs to an OTC status claim that this will lower drug prices and allow better access to treatment and fewer visits to the doctor. Opponents to reclassification have these arguments: (1) consumers may actually pay more because health insurance plans will not reimburse for OTC drug purchases, (2) excessive use of OTC drugs may increase the number of adverse drug–drug interactions, and (3) consumers may try to self-medicate serious illnesses instead of visiting their physicians for appropriate treatment.

Schedule Drugs Drugs with the potential for abuse and dependence were first regulated by The Harrison Narcotics Act of 1914. This act established the legal framework for controlling these drugs and introduced the word narcotic. This act was replaced in 1970 by The Comprehensive Drug Abuse Prevention and Control Act. Title II of this act, The Controlled Substances Act, established the Drug Enforcement Administration (DEA) in 1973 to regulate the manufacturing and dispensing of these drugs. The act also divided potentially addictive drugs into five categories or schedules based on their potential for physical or psychological dependence. These drugs are known as schedule drugs or controlled substances. The labeling and packaging for a controlled substance and all of its advertisements must clearly show the drug’s assigned schedule (see ■ FIGURE 1–9). The manufacturing, storage, dispensing, and disposal of controlled substances are strictly regulated by both federal and state laws.

■ FIGURE 1–9 Controlled substance symbol. The capital C stands for controlled substance. The number written inside (always a Roman numeral) indicates the assigned schedule. It is important to remember that a C with the Roman numeral IV inside it does not mean that the drug is to be given by the intravenous (I.V.) route; it means that the drug is a Schedule IV controlled substance.


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Schedule I Extremely high potential for abuse and addiction No currently accepted medical use Not available under any circumstances, even with a prescription Examples: heroin, LSD, marijuana, methaqualone, peyote, psilocybin


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■ FIGURE 1–10 Schedule II drug. OxyContin is a prescription drug that is used to treat severe pain. It is also a popular drug of abuse. Because it is a Schedule II drug—see the symbol on the label—it has a high potential for addiction. The drug bottle is sitting on a blue pill-counting tray in the pharmacy. This tray helps the pharmacist accurately count out the exact number of tablets specified in the patient’s prescription. The logo in the center of the tray reminds the pharmacist to “Check, Counsel, Communicate.”

Schedule II (see ■ FIGURE 1–10) High potential for abuse and addiction Currently accepted medical uses Requires an official prescription form Severe physical and psychological dependence may result Examples: cocaine, codeine, Demerol, Dilaudid, methadone, morphine, OxyContin, Percodan, Ritalin Schedule III Less potential for abuse and addiction than Schedule II drugs Currently accepted medical uses Moderate physical and psychological dependence may result Examples: anabolic steroid drugs, dronabinol (Marinol), Hycodan, paregoric, phenobarbital, testosterone, Tylenol w/ Codeine, Vicodin Schedule IV Less potential for abuse and addiction than Schedule III drugs Currently accepted medical uses Limited-to-moderate physical and psychological dependence may result Examples: Ambien, Darvon, Librium, Meridia, Sonata, Valium, Xanax

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Schedule V Limited potential for abuse Currently accepted medical uses Some physical and psychological dependence may result Examples: cough syrups with codeine, Lomotil


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Focus on Healthcare Issues There has been a longstanding debate over whether marijuana (a Schedule I drug) should be legally available to treat patients with certain medical conditions. In 1996, voters in California passed Proposition 215 to allow seriously ill patients to use marijuana if approved by their primary care physician. Eight other states passed similar laws. However, the federal law that prohibits the manufacturing and distribution of marijuana supersedes individual state laws. In November 2000, the U.S. Supreme Court agreed to hear a case that sought an exemption from the federal law for cases of medical necessity. The American Medical Association (AMA) advised that marijuana did provide medical benefit to patients with certain conditions, and many other groups supported the legalization of marijuana to varying degrees. In May 2001, however, the Supreme Court issued a decision that federal drug laws that ban the manufacture and distribution of marijuana allow for no exceptions, even for medical necessity. Despite this ruling, many patients do use the marijuana plant to treat themselves. Of note is that the main active ingredient in marijuana is available as the prescription drug dronabinol (Marinol). It is a Schedule III drug and is used to treat nausea and vomiting caused by chemotherapy and to stimulate the appetite in patients with HIV.

Physicians, dentists, podiatrists, nurse practitioners, and other healthcare providers whose state licenses allow them to may prescribe controlled substances. First, however, they must register with the federal Drug Enforcement Agency and be issued a DEA certificate and number to prescribe or dispense a schedule drug (controlled substance). The provider’s DEA number must be clearly written on any prescription for a schedule drug. In addition, some states require the healthcare provider to register with the state agency that controls schedule drugs and be issued a state certificate and number in order to prescribe or dispense schedule drugs in that state.

Orphan Drugs In 1983, The Orphan Drug Act was passed. Its purpose was to facilitate the development of new drugs to treat rare diseases. Normally, drug companies are reluctant to spend large amounts of time and money to research and test a drug if it will have a limited market. In the past that meant that drugs for rare diseases that only affected a few patients were not being developed. The Orphan Drug Act provided special incentives to a drug company, including grants to offset drug development costs, a tax credit that allowed the drug company to deduct up to 75 percent of the cost of clinical trials, a streamlined process for obtaining FDA approval, and exclusive marketing rights for seven years. This encouraged the development of orphan drugs to treat rare diseases, and now there are more than 1,000 orphan drugs.

Chapter Review Quiz Yourself


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1. Describe the linguistic origin/etiology of the following words. a. pharmacology b. medicine c. drug


2. 3. 4. 5.

6.

7. 8. 9. 10.

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11. 12. 13. 14. 15. 16.

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How are the definitions of drug and medicine the same? How are they different? Describe the three medical uses for drugs and give examples. Give the meaning of and describe the linguistic origin of the symbol Rx. Give the name of a drug in current usage that originated from the natural sources listed below. Natural Source Drug a. foxglove plant ________________ b. sheeps’ wool ________________ c. rose hips ________________ d. poppy ________________ e. mold ________________ f. periwinkle ________________ In what decade was each of the following drugs first introduced? Circle the correct answer. a. insulin 1890s 1900s 1910s 1920s 1930s 1940s b. penicillin 1890s 1900s 1910s 1920s 1930s 1940s c. aspirin 1890s 1900s 1910s 1920s 1930s 1940s d. cortisone 1890s 1900s 1910s 1920s 1930s 1940s e. vitamin A 1890s 1900s 1910s 1920s 1930s 1940s f. phenobarbital 1890s 1900s 1910s 1920s 1930s 1940s g. Viagra 1950s 1960s 1970s 1980s 1990s 2000s h. Tagamet 1950s 1960s 1970s 1980s 1990s 2000s i. Librium 1950s 1960s 1970s 1980s 1990s 2000s j. 1st recombinant DNA drug 1950s 1960s 1970s 1980s 1990s 2000s k. Thorazine 1950s 1960s 1970s 1980s 1990s 2000s l. Gardisil 1950s 1960s 1970s 1980s 1990s 2000s m. Inderal 1950s 1960s 1970s 1980s 1990s 2000s n. H2 blocker drugs 1950s 1960s 1970s 1980s 1990s 2000s o. Nicoderm 1950s 1960s 1970s 1980s 1990s 2000s p. First drug for HIV 1950s 1960s 1970s 1980s 1990s 2000s q. Botox 1950s 1960s 1970s 1980s 1990s 2000s Name three ancient “medicines” that seem silly or outrageous to us today. Is it possible that some of the “medicines” you named for Question 7 could be found to have some therapeutic value in the future? State the reason for your answer. In the 1700s and 1800s, drugs frequently contained addictive ingredients not listed on the label. Name two such ingredients. Describe the social and consumer safety circumstances that led to the passage of each of these drug laws. a. The Food and Drugs Act of 1906 b. The Food, Drug, and Cosmetic Act of 1938 c. Kefauver-Harris Amendment of 1962 d. FDA Modernization Act of 1987 What federal agency is empowered to review data on a drug’s safety and clinical effectiveness and approve drugs for marketing? What is a Compassionate Use IND application? Define the following phrases: prescription drug, over-the-counter drug. Describe how The Controlled Substances Act categorized drugs of potential abuse. What is the purpose of the 1983 Orphan Drug Act? What three incentives does it offer to drug companies to develop orphan drugs? What part of the wording of a drug label tells you that it is a prescription drug?


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17. Why was the drug thalidomide, which caused severe birth defects in thousands of babies, allowed on the market again? 18. What is the meaning of this symbol?

Clinical Applications 1. In 2001, the manufacturer of lovastatin (Mevacor) asked the FDA to allow this prescription drug to switch from being a prescription drug to being an OTC drug. The FDA did not approve this change. Describe the four criteria mentioned in this chapter for prescription-toOTC approval. Explain why you think the FDA OTC Drugs Advisory Committee ruled against this request? If you had been on the committee, would you have voted for or against approving this drug for OTC use? (Hint: Look up lovastatin in Appendix D of this textbook and see what category of drugs it belongs to; then look up that category of drugs in Chapter 11 and read about it.) 2. You are caring for a patient who is extremely ill but might be able to be helped if he could get access to a drug that is already approved in Europe. Write a paragraph criticizing the time lag in the United States for the approval of new drugs that are already in clinical use in other countries. Give a drug example to support your position. 3. You read in the newspaper about an FDA-approved drug that has now suddenly been withdrawn from the market because of causing serious adverse reactions and several deaths. Write a paragraph defending the time needed to investigate drugs before approving them. Give a drug example to support your position. 4. Look at this drug label and answer the following questions. a. What is the name of this drug? b. To what schedule does this drug belong? c. Is this a prescription drug or an over-the-counter drug? How can you tell?

Multimedia Extension Exercises Go to www.pearsonhighered.com/turley and click on the photo of the cover of Understanding Pharmacology for Health Professionals to access the interactive Companion Website created for this textbook.


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