Understanding Pharmacology for Health Professionals

Unit One

THE PAST HISTORY,PRESENT USES, ANDFUTURE OF DRUGSChapter 1Introduction to Pharmacology and the History of Drugs

Chapter 2Drug Design, Testing, Manufacturing, and Marketing

Chapter 3Drug Forms

Chapter 4Routes of Administration and the Drug Cycle

Chapter 5Using Drugs Therapeutically

Chapter 6The Prescription

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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.

Introduction to Pharmacologyand the History of Drugs

CHAPTER CONTENTS

Origins of Pharmacology WordsMedical Uses for DrugsDrugs in Ancient TimesModern Drugs Derived from Natural

SourcesDrugs in the 1800s and 1900sPharmaceutical TimelineMislabeled and Dangerous Drugs

Drug Legislation and Drug AgenciesPrescription and Over-the-Counter

DrugsSchedule DrugsOrphan DrugsQuiz YourselfClinical ApplicationsMultimedia Extension Exercises

Learning ObjectivesAfter you study this chapter, you should be able to

1. Describe the origin of the words pharmacology, drug, medicine, and other wordsrelated 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 mineralsources 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.

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

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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CHAPTER 1 • INTRODUCTION TO PHARMACOLOGY AND THE HISTORY OF DRUGS 3

Pharmacology 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 pharma-cology is amazing in its scope, ranging from the historical and present day uses of herbsand plant extracts to day-to-day painstaking research that produces unusable productsas well as life-saving drugs to the future with genetic manipulation, molecular pharma-cology, adult stem cell therapy, and a seemingly limitless potential for discovery.

Origins of Pharmacology WordsPharmacologyPharmacology is the study of drugs and their interactions with living organisms. The wordpharmacology comes from the Greek word pharmakon, which means medicine or drug, and thesuffix -logy, which means the study of. Pharmacology is concerned with the nature of drugs, theireffects in the body, drug doses, side effects, and so forth.

Pharmacology is a general word. Other more specific words related to specialty fields withinthe field of pharmacology include the following:

molecular pharmacology the study of the chemical structures of drugs and the effects of drugs atthe molecular level within cells

pharmacodynamics the mechanisms of action by which drugs produce their effects (desired orundesired) based on time and dose

pharmacogenetics how the genetic makeup of different people affects their responses to certaindrugs

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 MedicinesThe word drug is derived from the Dutch word droog, which means dry, and refers to the use ofdried herbs and plants as the first medicines. The Latin word for drug is medicina, from which wederive the words medicine and medication. A drug or a medicine can be thought of as any nonfoodchemical substance that affects the mind or the body. The word medicine refers to a drug that isdeliberately 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, butdrug can also refer specifically to chemical substances that do not have a preventive, diagnostic, ortherapeutic use (e.g., illicit or street drugs).

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

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

1. Preventive use. Drugs are used to prevent the occurrence of diseases or conditions. Theadministration of a preventive drug is known as prophylaxis. Prophylaxis is from a Greekword meaning to keep guard before. Examples of the preventive uses of drugs include thefollowing:■ 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 thediagnostic 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.

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

■ FIGURE 1–2 Preventive use of drugs.Dramamine is an over-the-counter drug that is taken to preventmotion sickness and vomiting. The word vomiting does notappear on the drug package, but the word antiemetic, whichmeans pertaining to against vomiting, appears at the top right.

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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 thera-peutic 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.

Drugs in Ancient TimesPharmacology is one of the oldest branches of medicine. Ancient peoples such as the Sumerians andEgyptians recorded the use of drugs on clay tablets, on wall paintings in tombs, and on papyrus asearly 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 basisas, many centuries later, penicillin was extracted from a mold. An Egyptian medicinal scroll, theEbers Papyrus from 1500 B.C. (discovered in the early 1800s), contained the names of 800 differentherbal formulations and prescriptions. The Egyptians also extracted the oil from various plantsknown for their healing properties. In 1922 when King Tutankhamun’s tomb was opened, archeolo-gists 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 withacupuncture, massage, and exercise. Shen Nong completed the first Chinese book on herbal medi-cine in 3494 B.C. It included 365 different herbal remedies.

Clinical ApplicationsThe American Academy of Pediatrics issues an annual immunization schedule for preventingchildhood diseases. All children must receive certain immunizations before they are permittedto enroll in school. Exceptions are granted for religious reasons or when immunizations aremedically inadvisable.

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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 manyherbs with medicinal properties. Aztec King Montezuma maintained royal gardens of medici-nal plants.

The Greeks and Romans furthered the study of medicine through an understanding of anatomyand physiology, which was an important first step toward understanding how drugs exert theireffects in the body.

Ancient drugs were prepared according to standard recipes that involved drying, crushing, andcombining a variety of plants, substances from animals, or minerals. The symbol Rx, which comesfrom the Latin word recipe, meaning take, indicates a prescription, the combining of ingredients toform a drug. The use of some ingredients was based on medical lore and superstition. Some ingre-dients had therapeutic value, but others were worthless or actually harmful.

Medieval physicians prescribed a broad range of drugs from herbs to metals (e.g., powderedgold) to addictive substances (e.g., opium). In the 1600s, patients were advised to eat soap to cureblood in the urine and put mercury in beer to cure intestinal worms. Because little was known abouteven the most fundamental physical and chemical processes of the body, the therapeutic use ofdrugs was not an exact science.

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

Drugs Derived from PlantsThe 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 totreat congestive heart failure.

■ FIGURE 1–3 Chinese herbal medicines.This Chinese pharmacist prepares herbal medicines in much thesame way that his ancestors did, by using dried herbs which arethen crushed into powder. He is making four batches of the samemedicine, each of which contains the same mixture of herbs. Thewall behind him holds drawers of many different types of driedherbs. In 1970, the Chinese Academy of Medical Science compileda collection of traditional herbal remedies. American pharmacistsevaluated those remedies and found that 45 percent of them weretherapeutic, according to Western standards of medicine.

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The belladonna plant was the original source of two drugs that are still in use today—atropineand 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 withinflammatory 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 induceeuphoria and a trance-like state. The sap from the seedheads of the poppy flower Papaver somniferumcontain 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 wereburned and used by the ancient Chinese to treat respiratory ailments. Today, ephedrine is present inover-the-counter bronchodilator drugs.

■ FIGURE 1–4 Foxglove plant.This beautiful wild flowering plant is commonly known as foxglove, butits scientific name is Digitalis lanata. The drug digitalis (which is nolonger in use) came from this plant, as does the modern drug digoxin(Lanoxin), which is used to treat congestive heart failure.

Did You Know?Herbs have been a part of all cultures for centuries and have been mentioned frequently in liter-ature. Henbane, a very toxic herb, was supposed to have been the poison that Claudius used tokill his brother, Hamlet’s father. ”Henbane should not be confused with wolfsbane. Students ofliterature know wolfsbane to be useful as a vampire repellant (Dracula, 1897); however, weshould point out that double-blind studies demonstrating the effectiveness of this plant havenot 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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■ 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 insome over-the-counter vitamin C dietary supplements. Otherproducts use synthetic vitamin C.

Some estrogen hormone replacement therapy drugs are derived from yams. The drug galanta-mine (Razadyne), which is used to treat Alzheimer’s disease, is derived from daffodil bulbs. In addi-tion, many of the gums, oils, and bases in which drugs are dissolved come from plant sources. Manydrugs contain soybean oil, sesame seed oil, or olive oil.

Other plants have also become the sources of some modern drugs (see ■ TABLE 1–1).

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Drugs Derived from AnimalsThyroid supplement drugs are composed of dried (desiccated) thyroid gland tissue taken from ani-mals. Thyroid supplement drugs are used to treat patients with hypothyroidism.

The drug Premarin, a female hormone replacement drug used to relieve the symptoms ofmenopause, is derived from pregnant mares’ urine, and the trade name is formed from selected let-ters taken from that phrase.

Lanolin, a common ingredient of topical skin drugs, is obtained from the purified fat ofprocessed sheeps’ wool.

In the past, the only source of insulin used to treat diabetes mellitus was from ground-up animalpancreas (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 frompork (in vertical capital letters).

Drugs Derived from MineralsMinerals, such as calcium and iron, are available as individual dietary supplements, and traceminerals, such as copper, magnesium, selenium, and zinc, are included in many multivitaminsupplements. Centrum multivitamins use the advertising slogan “From A to Zinc,” to show thatthey contain vitamins and minerals alphabetically from vitamin A through zinc.

Potassium, in the form of potassium chloride, is given in conjunction with diuretic drugsbecause diuretic drugs cause increased excretion of potassium (and water).

The cardiac drug quinapril (Accupril) contains red iron oxide as an inert ingredient in its browntablets.

Drugs in the 1800s and 1900sIt was not until the 1800s that chemists developed techniques to extract and isolate pure substancesfrom crude drug preparations. The isolation of morphine in 1803 by a German pharmacist markedthe beginning of modern drug therapy using chemically pure ingredients.

In the early 1900s, the extraction and preparation of drugs was still a time-consuming processthat utilized test tubes, filters, and Bunsen burners. Pharmacists at that time actually prepared thedrugs they dispensed. Daily, they made milk of magnesia, paregoric, and syrup bases for liquidmedicines. In addition, they hand-rolled cocoa butter suppositories. They measured out drugs inminims, drams, ounces, grains, and scruples (the apothecary system of measurement).

Much has changed since then. Many drugs are now completely synthetic rather than derivedfrom natural sources. Other natural drugs have undergone chemical modification and molecularrestructuring to create new drugs that possess superior pharmacologic action. In addition, the phar-macist no longer prepares drugs, but dispenses them and provides patient information and education.

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

(continued)

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

Year Major Pharmaceutical Milestone

1803 Morphine isolated from crude opium

1827 Merck & Company, a German drug company, begins the first commercial production of morphine

1843 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)

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

Year Major Pharmaceutical Milestone

1983 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 tissueplasminogen 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 Helicobacterpylori

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 antibioticdrugs 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 prescriptionand over-the-counter forms

2007 Isentress introduced (first integrase inhibitor drug for HIV)

2008 Xenazine introduced (first FDA-approved drug for Huntington’s disease)

(continued)

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■ 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.

Mislabeled and Dangerous DrugsFrom the early history of pharmacology, most physicians attempted to treat patients based on whatlittle scientific knowledge was available to them. As early as 2100 B.C., the Code of Hammurabigave severe penalties for malpractice.

However, throughout medical history many ineffective, mislabeled, and even dangerous drugshave 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 forDiabetes, Dr. Shreve’s Anti-Gallstone Remedy, and Anti-Morbific Great Liver and KidneyMedicine were commonly sold without regulation and were accompanied by extravagant claims ofcures. 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 respiratoryailments, contained cherry flavoring and heroin. Even when a drug included the name of the addic-tive ingredient in its title or on its label (see ■ FIGURE 1–7), consumers were often not aware ofits addictive qualities. One drug prescribed for respiratory ailments, hydrocyanic acid, causedmany deaths. (This poison, which as a gas contains cyanide, is used for legal executions.)

It is estimated that in the early 1900s one out of every 200 Americans was addicted, most ofthem 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 drugside effects did not exist. At that time, the prevailing dictum was “Let the buyer beware.”

Drug Legislation and Drug AgenciesLaws were passed in the 1900s to protect the public from unscrupulous drug sellers, as well as fromworthless, mislabeled, and dangerous drugs that were then on the market. The drug manufacturersstrongly opposed drug laws, but public outrage resulted in the passage of The Food and Drugs Actof 1906, the first federal drug law. A 1912 amendment to this act required the accurate labeling ofdrugs 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, manyworthless drugs remained on the market because the burden of proof lay with the government toshow 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 anextensive advertising campaign aimed at physicians, a Tennessee company marketed this drug in araspberry-flavored base and called it “Elixir of Sulfonamide.” This base had been tested by the man-ufacturer 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 takingless than one ounce of this drug, and over 350 individuals were poisoned. At that time, a drug man-ufacturer did not need FDA approval before marketing a drug. Because of this tragedy, Congresspassed The Food, Drug, and Cosmetic Act of 1938 that previously had lacked the support itneeded to pass. As a result, the government no longer needed proof of fraud to stop the sale of adrug. It could seize any drug suspected of being toxic. Secondly, the burden of proof was shifted tothe drug manufacturers, who were required to provide data based on scientific experiments to showthat their product was safe before they were allowed to market it. It became the job of the Food andDrug 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 definedprescription 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 exten-sively during early pregnancy to treat morning sickness in women. The FDA refused to approve itsuse in the United States without further studies. Before these additional studies could be completedby the manufacturer, evidence against the safety of the drug began to accumulate. Over 8,000 babiesin Europe were born with deformed limbs (“seal limbs,” or phocomelia). This tragedy resulted inthe 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 beshown to be both safe and effective before being marketed. It also required manufacturers to reportadverse side effects from new drugs. Since that time, many drugs have been kept from the market orhave been removed from the market because of a lack of safety.

Historical NotesBecause of its devastating adverse effects in unborn children, thalidomide would have beenrelegated to an obscure footnote in medical history, but in 1997 it was discovered to be auseful drug in treating cancer, AIDS, and leprosy. The potential adverse effects of this drugare so great that it is only considered as a viable treatment option for these life-threateningdiseases. The FDA regulates the use of thalidomide in two ways: (1) by limiting the numberof physicians who can prescribe it and (2) by requiring women taking the drug not to havesexual intercourse or to use two forms of birth control (so that there is virtually no risk ofthem giving birth to a child with phocomelia). Thalidomide is now an official prescriptiondrug used to treat multiple myeloma, leprosy, graft-versus-host disease, and several types ofcancers. It is also officially recognized as an orphan drug that is used to treat wasting syn-drome 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 ben-efits. To do this thoroughly, the FDA must take the time to complete its review process before itissues a final approval (or rejection) of a new drug. In 1988, the Food and Drug Administration wasmoved under the federal Department of Health and Human Services.

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In 1994, the Dietary Supplements and Health and Education Act was passed. This legislationallowed the FDA to set up guidelines for the manufacturers of herbal products and dietary supple-ments (see ■ FIGURE 1–8). Although the FDA could not regulate these products and the productswere still available without a prescription, the drug manufacturers were now liable for any claimsagainst 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, forcertain critical drugs the process could be much shorter. The first drug effective against HIV wasapproved 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 drugswere available in other countries for quite some time before they received approval by the FDAfor use in the United States. For example, Inderal, a widely used drug for hypertension andarrhythmias, was available in Europe for nearly 10 years before it was finally approved for use inthe United States in 1967. In response to this criticism, the FDA made a concerted effort tostreamline the approval process, particularly with respect to drugs used to treat life-threateningdiseases. In 1996, indinavir (Crixivan), a protease inhibitor drug used to treat HIV, was approvedby 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. By2000, the average review time for new drugs had fallen to less than 15 months. Critically neededdrugs (as well as those for whom the drug manufacturer pays a special fee) can be approved in aslittle as 6 months.

In addition, the FDA allows physicians to prescribe some investigational drugs even beforethey are officially approved for marketing. These drugs are for life-threatening diseases for whichno other alternative therapy exists. In order to prescribe such a drug, the FDA requires anEmergency Treatment Investigational New Drug (IND) application to be filed. This is alsoknown as a Compassionate Use IND application. In the 1970s, long before the cardiac drug amio-darone (Cordarone) was on the market (final approval, 1985), cardiologists prescribed it as an inves-tigational new drug to treat patients with life-threatening cardiac arrhythmias that did not respond toother antiarrhythmic drugs. Similarly, the first drug for HIV was prescribed for patients before itsapproval in 1987. This was done under a Compassionate Use IND application.

Under the federal regulations of HIPAA (pronounced “hip-ah”), the Health InsurancePortability and Accountability Act of 1996, all healthcare settings must provide patients with astatement that verifies that their health record information, including all drug information, is kept

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

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

Generic NamePrescription TradeName 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

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

Prescription and Over-the-Counter DrugsThe Food and Drug Administration (FDA) regulates prescription drugs and over-the-counterdrugs. Prescription drugs are defined as those drugs that are not safe to use except under profes-sional medical supervision. Prescription drugs can only be obtained with a written prescription orverbal order from a physician, dentist, nurse practitioner, or other healthcare provider whoselicense permits this. Prescription drugs are also known as legend drugs because the drug manufac-turer and pharmacist add one of these two legends (inscriptions) to the drug package and to thefilled 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. AnOTC drug is defined as one that can be purchased without a prescription and is generally consideredsafe for consumers to use if the label’s directions and warnings are followed carefully. OTC drugscomprise 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 andmany other drugs followed. The OTC drug is the same as the original prescription drug, but the rec-ommended dose is usually just a fraction (often half) of the dose of the prescription drug. An excep-tion to this is cetirizine (Zyrtec), a prescription antihistamine drug whose over-the-counter dose, asapproved 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 drugsand determining which ones were safe and appropriate for over-the-counter use (see ■ TABLE 1–3).

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

Schedule DrugsDrugs with the potential for abuse and dependence were first regulated by The Harrison NarcoticsAct of 1914. This act established the legal framework for controlling these drugs and introduced theword narcotic. This act was replaced in 1970 by The Comprehensive Drug Abuse Preventionand Control Act. Title II of this act, The Controlled Substances Act, established the DrugEnforcement Administration (DEA) in 1973 to regulate the manufacturing and dispensing ofthese drugs. The act also divided potentially addictive drugs into five categories or schedules basedon their potential for physical or psychological dependence. These drugs are known as scheduledrugs or controlled substances. The labeling and packaging for a controlled substance and all of itsadvertisements must clearly show the drug’s assigned schedule (see ■ FIGURE 1–9). The manu-facturing, storage, dispensing, and disposal of controlled substances are strictly regulated by bothfederal 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 importantto remember that a C with the Roman numeral IV inside it does not meanthat the drug is to be given by the intravenous (I.V.) route; it means thatthe drug is a Schedule IV controlled substance.

Supporters of the reclassification of some prescription drugs to an OTC status claim that thiswill 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 morebecause health insurance plans will not reimburse for OTC drug purchases, (2) excessive useof OTC drugs may increase the number of adverse drug–drug interactions, and (3) con-sumers may try to self-medicate serious illnesses instead of visiting their physicians for appro-priate treatment.

Focus on Healthcare Issues

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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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


Moderate physical and psychological dependence may result

Examples: anabolic steroid drugs, dronabinol (Marinol), Hycodan, paregoric, phenobar-bital, testosterone, Tylenol w/ Codeine, Vicodin

Schedule IV

Less potential for abuse and addiction than Schedule III drugs


Limited-to-moderate physical and psychological dependence may result

Examples: Ambien, Darvon, Librium, Meridia, Sonata, Valium, Xanax

Schedule V

Limited potential for abuse


Some physical and psychological dependence may result

Examples: cough syrups with codeine, Lomotil

■ 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 IIdrug—see the symbol on the label—it has a high potential foraddiction. The drug bottle is sitting on a blue pill-counting tray inthe pharmacy. This tray helps the pharmacist accurately count outthe 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.”

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

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

Chapter Review

Quiz Yourself1. Describe the linguistic origin/etiology of the following words.

a. pharmacologyb. medicinec. drug

There has been a longstanding debate over whether marijuana (a Schedule I drug) should belegally available to treat patients with certain medical conditions. In 1996, voters in Californiapassed Proposition 215 to allow seriously ill patients to use marijuana if approved by theirprimary care physician. Eight other states passed similar laws.

However, the federal law that prohibits the manufacturing and distribution of marijuanasupersedes individual state laws. In November 2000, the U.S. Supreme Court agreed to heara case that sought an exemption from the federal law for cases of medical necessity. TheAmerican Medical Association (AMA) advised that marijuana did provide medical benefit topatients with certain conditions, and many other groups supported the legalization of mari-juana to varying degrees. In May 2001, however, the Supreme Court issued a decision thatfederal drug laws that ban the manufacture and distribution of marijuana allow for noexceptions, even for medical necessity.

Despite this ruling, many patients do use the marijuana plant to treat themselves. Of noteis 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 bychemotherapy and to stimulate the appetite in patients with HIV.

Focus on Healthcare Issues

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2. How are the definitions of drug and medicine the same? How are they different?3. Describe the three medical uses for drugs and give examples.4. Give the meaning of and describe the linguistic origin of the symbol Rx.5. Give the name of a drug in current usage that originated from the natural sources listed

below.Natural Source Druga. foxglove plant ________________b. sheeps’ wool ________________c. rose hips ________________d. poppy ________________e. mold ________________f. periwinkle ________________

6. In what decade was each of the following drugs first introduced?Circle the correct answer.a. insulin 1890s 1900s 1910s 1920s 1930s 1940sb. penicillin 1890s 1900s 1910s 1920s 1930s 1940sc. aspirin 1890s 1900s 1910s 1920s 1930s 1940sd. cortisone 1890s 1900s 1910s 1920s 1930s 1940se. vitamin A 1890s 1900s 1910s 1920s 1930s 1940sf. phenobarbital 1890s 1900s 1910s 1920s 1930s 1940sg. Viagra 1950s 1960s 1970s 1980s 1990s 2000sh. Tagamet 1950s 1960s 1970s 1980s 1990s 2000si. Librium 1950s 1960s 1970s 1980s 1990s 2000sj. 1st recombinant DNA drug 1950s 1960s 1970s 1980s 1990s 2000sk. Thorazine 1950s 1960s 1970s 1980s 1990s 2000sl. Gardisil 1950s 1960s 1970s 1980s 1990s 2000s

m. Inderal 1950s 1960s 1970s 1980s 1990s 2000sn. H2 blocker drugs 1950s 1960s 1970s 1980s 1990s 2000so. Nicoderm 1950s 1960s 1970s 1980s 1990s 2000sp. First drug for HIV 1950s 1960s 1970s 1980s 1990s 2000sq. Botox 1950s 1960s 1970s 1980s 1990s 2000s

7. Name three ancient “medicines” that seem silly or outrageous to us today.8. 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.9. In the 1700s and 1800s, drugs frequently contained addictive ingredients not listed on the

label. Name two such ingredients.10. 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 1906b. The Food, Drug, and Cosmetic Act of 1938c. Kefauver-Harris Amendment of 1962d. FDA Modernization Act of 1987

11. What federal agency is empowered to review data on a drug’s safety and clinical effectivenessand approve drugs for marketing?

12. What is a Compassionate Use IND application?13. Define the following phrases: prescription drug, over-the-counter drug.14. Describe how The Controlled Substances Act categorized drugs of potential abuse.15. What is the purpose of the 1983 Orphan Drug Act? What three incentives does it offer to drug

companies to develop orphan drugs?16. 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 Applications1. 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 notapprove this change. Describe the four criteria mentioned in this chapter for prescription-to-OTC approval. Explain why you think the FDA OTC Drugs Advisory Committee ruledagainst this request? If you had been on the committee, would you have voted for or againstapproving this drug for OTC use? (Hint: Look up lovastatin in Appendix D of this textbookand see what category of drugs it belongs to; then look up that category of drugs in Chapter 11and read about it.)

2. You are caring for a patient who is extremely ill but might be able to be helped if he could getaccess to a drug that is already approved in Europe. Write a paragraph criticizing the time lagin the United States for the approval of new drugs that are already in clinical use in othercountries. Give a drug example to support your position.

3. You read in the newspaper about an FDA-approved drug that has now suddenly been with-drawn from the market because of causing serious adverse reactions and several deaths. Writea paragraph defending the time needed to investigate drugs before approving them. Give adrug 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 createdfor this textbook.

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Understanding Pharmacology for Health Professionals

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