Key Questions

TIPS FOR THE TEACHER

            Typical doses of aspirin and acetaminophen are 325mg and for ibuprofen, 200mg. These drugs have drawbacks. Aspirin causes intestinal bleeding and may cause               allergies. It has been implicated in Reye’s syndrome, a life-threatening condition that may follow flu or chicken pox in children and teenagers. Acetaminophen is               not useful to patients with arthritis, and it is toxic to the liver in large doses. Ibuprofen causes intestinal bleeding and impairs kidney function.

6. Narcotic analgesics are used to obtain higher levels of pain relief (e.g., the pain associated with fractures, kidney stones, heart attack, gallstones) than can be achieved with the OTC aids. They produce stupor or insensibility as well as addiction and withdrawal symptoms and increasing tolerance. Narcotic analgesics include codeine, morphine, and meperidine (DemerolÔ). Morphine is found naturally in the opium poppy. Codeine is made by methylating (substituting the CH 3 – group for H–) morphine. Meperidine is a synthetic narcotic. The dose for pain relief of these analgesics is typically 5–120mg.

10. Local anesthetics render one part of the body insensitive to pain. Benzocaine is available in some OTC preparations for localized surface pain and itching. Procaine and lidocaine are more potent and are used in dental repair or for minor surgery.

        Tetracycline antibiotics get their name from their four-ring structure. First used in 1950, they are effective against a wide variety of microorganisms. Initially obtained           from fungi, many tetracyclines are synthesized today. Terramycin is a typical example.

14. Nicotine and Smoking. People smoke for enjoyment, to alleviate stress, or because they are addicted to nicotine. Yet nicotine, the active ingredient in tobacco, is toxic. It is lethal at doses of about 60mg, and a typical cigar contains at least 120mg. However, only about 10% of that amount is absorbed on inhaling the smoke, and over a relatively long period. A typical filter cigarette contains 20-30mg of nicotine. Low doses of nicotine increase respiratory rate, stimulate an increased heart rate and blood flow, and constrict the arteries. Regular smokers exhibit a shortness of breath because CO and HCN formed in the combustion processes bind to hemoglobin, diminishing its ability to carry oxygen. At high doses, nicotine interferes with nerve impulse transmission. Tolerance can be developed for small amounts of nicotine along with a dependency.

It is not just the nicotine in cigarettes that is harmful.Benzpyrene, found in tobacco smoke, is an extremely carcinogenic compound. Tobacco also contains b-naphthylamine, which causes bladder cancer.

Individuals chewing or dipping smokeless tobacco have a particularly dangerous habit. Smokeless tobacco causes tooth decay (it has a high sugar content), gum disease, and oral cancer. Nicotine levels in the blood of smokeless tobacco users is comparable to or greater than cigarette smokers.

15. Caffeine is found in tea, coffee, and cola drinks. Caffeine is an alkaloid (i.e., can be extracted from its natural source by acid) and a stimulant. It causes an increased alertness, the ability to put off sleep, and an increased capacity for thinking, but coordination and timing may be adversely affected. It is the main ingredient in certain OTC products, such as No-Doz (100mg caffeine per dose) and Vivarin (200mg per dose). Caffeine users can develop tolerance and dependency. Coffee drinkers (90mg/ cup) will experience lethargy, headache, or nausea after abstaining for up to 15 hr. Cola drinkers (43mg/can) and tea drinkers (50mg/ cup) can also experience these reactions.

        Ethyl alcohol is detoxified by a liver enzyme through an oxidation reaction. In individuals who develop tolerance for alcohol, increasing amounts of the enzyme build up           in the liver enabling large amounts of alcohol to be detoxified.

17. Benzedrine is a mixture of two optical isomers of amphetamine. These two isomers differ in the way they rotate plane polarized light. These isomers occur because of the four different groups (C 6 H 5 CH 2 –, NH 2 –, CH 3 –, and H–) around the central carbon atom. Dexedrine is the stronger stimulant of the two. Amphetamines are central nervous system stimulants that increase heart rate and blood pressure. They increase wakefulness, drive, and energy. They produce a temporary elevation of mood, usually followed by fatigue, irritability, and depression. Users often must take barbiturates to sleep. Amphetamines have been used for weight reduction and to relieve mild depression. In colloquial language, amphetamines are called "uppers."

            Both diagnostic and therapeutic radioisotopes typically produce gamma radiation. In low doses, gamma radiation is less harmful to tissues than alpha or beta              radiation. Although alpha and beta radiation produce more cell deaths per unit of exposure than gamma radiation, the penetrating power and ranges of alpha and              beta radiation are very small. Gamma radiation penetrates tissues very effectively and, in high dosages, is very effective in causing cell death, particularly in rapidly              multiplying cells. For this reason, gamma radiation is used for therapeutic purposes as well. Typically a beta emitter like cobalt-60 is used for cancer treatment. An              atom of cobalt-60 transmutes to a highly excited atom of nickel-60, which emits two high-energy gamma rays in quick succession. These gamma rays have been              found to be effective in the treatment of some types of cancer.

21. Anticancer Drugs. Cancer is cell multiplication without restraint with invasion of nearby tissue. In addition to surgical removal of affected areas and irradiation to kill the cancer cells, cancers are treated by chemotherapy use of chemical substances to kill cancer cells. These substances include alkylating agents, cisplatin, and antimetabolites. Alkylating agents are organic compounds that transfer alkylating groups to nitrogen bases (usually guanine) in DNA. The presence of the alkyl group in guanine prevents DNA replication (and thus, cell division). Cisplatin also blocks DNA replication. Antimetabolites interfere with synthesis of a nucleotide necessary for DNA synthesis and therefore inhibit cell division. 5-Fluorouracil is an antimetabolite (see Drug Design in Links and Connections section). The use of these substances is based on the premise that cancer cells are undergoing rapid division and will be affected to a greater extent than healthy cells. In the long run, healthy cells suffer as well. Chemotherapy has provided an improvement in patient survival with some cancers, particularly breast, bladder, and colon cancer, and Hodgkin’s disease.

Drugs are not good or bad in themselves. They may be used properly or abused. Similarities in structural formulas of drugs cause similar physiological responses.

Classroom discussion is particularly important in this module. Suggested points for discussion are indicated below.

1. Why do people smoke or use drugs if we know that they are bad for you? (The discussion will avoid judgmental aspects and will address the social problem.)
2. How is the legal use of alcohol and cigarettes different from the illegal use of pleasure drugs?
3. To what extent is the use of anesthetics warranted in ordinary cuts and bruises, dentistry, and childbirth?
4. At what point in an illness should the decision to use or terminate chemotherapy occur?

For centuries, humans have eaten or chewed berries, bark, roots, and herbs to alleviate or cure sickness or disease. The origin of disease was unknown, and its treatment was coupled with magic and superstition. However, the scientific practice of medicine began in ancient Asiatic civilizations. The first known code of medical ethics was established in Sumer. The ancient practice of acupuncture and ideas about blood circulation suggest that the Chinese were familiar with anatomy, vascular systems, and the nervous system. In addition to introducing the Hippocratic oath, the Greeks advanced medical knowledge in anatomy and physiology, diet, and exercise. Through their sanitation facilities, the Romans improved public health. Medical knowledge began to decline during the Middle Ages in Europe, but Arab and Jewish physicians made some progress. For example, two Persians introduced opium for coughs and extracts of crocus seeds to treat gout. Both of these remedies are in use today.

The ancients knew that chewing willow tree (Genus: Salix) bark had an analgesic effect. Centuries later, the active ingredient was isolated from the willow bark and called salicylic acid in deference to its origin.

Jesuit missionaries introduced an important herbal remedy into Europe in the 17th century. This remedy was an extract of cinchona bark obtained from South American Indians. The extract was used by Indians against chills and fever and soon became a favorite anti-malarial medicine in Europe. The principal ingredient of cinchona bark is quinine. Also, in the 17th century, William Harvey demonstrated blood circulation and the heart as a pump. A major step toward diagnosing disease was made with the introduction of the compound microscope, making minute forms of life visible for the first time. The 18th century witnessed the introduction of vaccination by Edward Jenner. Modern medicine had its birth in the 19th century with the development of the germ theory of disease, the use of anesthesia (Crawford Long, 1842), antiseptics in surgery (Joseph Lister, 1867), and a revival of public health measures and better sanitation. During the 20th century there has been an increased understanding of immunity, the endocrine system, and the importance of vitamins and nutrition, advances in surgery, organ transplants, and diagnostic techniques (CAT scan, MRI, etc. ). Chemotherapy is an important development of the 20th century. Specific drugs have been discovered and designed to eliminate disease-causing microorganisms (antibiotics), to rectify a hormonal imbalance (insulin), and to arrest a cancerous growth (anticancer drugs).

The following are three interesting stories  related to chemistry in medicine. The first two are taken from Men of Medicine by Katherine Shippen (1957). The last is from Medical Heroes and Heretics by Wayne Martin (1977).

Who Discovered Anesthesia?

In the eighteenth century, the English chemist Humphry Davy made dinitrogen oxide (N 2 O, nitrous oxide, laughing gas), and observed that it prevented feeling physical pain. He thought it might be useful in surgery, but did nothing about it. It wasn’t until the next century that a true anesthetic was made, although its discoverer has not yet been satisfactorily determined.

In 1914, Alexander Fleming, physician in the Royal Army Medical Corps, observed that many soldiers wounded in combat developed blood poisoning, pneumonia, or some other bacterial infection. Fleming knew there was need for an effective antiseptic to fight the infections, but none was available.

After the war, Fleming began to teach bacteriology at St. Mary’s Hospital in London. He spent many hours in the laboratory searching for the microbe-destroying agent he had needed during the war. One day in 1928, he observed through his microscope that a mold fleck had settled on one culture plate of bacterial growth sitting next to an open window. At first he was annoyed that the mold had contaminated the plate. About to throw it away, he stopped and examined the plate again. The mold was being surrounded by a halo of watery fluid, and he surmised that something in the mold was destroying the microbes. He removed the mold and grew more of it. At first it was fuzzy white, then it turned green, spreading fronds that matted together in a thick mass. Fleming and his assistants continued to study the watery fluid secreted by the mold and found that it was effective against germs causing blood poisoning, sore throat, some types of pneumonia, but not typhoid fever or dysentery. It did not affect blood serum as he had feared it might, nor did it harm mice and rabbits. He concluded that it could be applied to the infected surface undiluted, and it was nonirritating and nontoxic. He named the new antiseptic penicillin, after the penicillium family to which the mold belonged.

In 1929, Fleming published a paper announcing the discovery of penicillin. The tiny amounts of penicillin that Fleming could make in the laboratory were not enough to treat a single patient, so his discovery did not arouse much interest. His paper lay forgotten on the library shelves for nearly 10 years until, in 1939, an Australian physician, Howard Florey, reread it and contacted Fleming. Fleming sent Florey some of the original mold, and from it Florey eventually isolated about a teaspoonful of penicillin—enough to treat one case of infection. He soon had the opportunity to find out if it worked: as a last resort he administered the penicillin to a policeman with a severe case of blood poisoning. The penicillin combated the blood poisoning effectively as long as it continued to be administered, but the single teaspoonful was not enough. When the penicillin ran out, the blood poisoning returned, and the patient died. Florey knew that larger amounts of penicillin would have to be made on a commercial scale. Because England was involved in a war in 1941, Florey went to the United States where penicillin could bemass-produced. By 1943, it was being used to treat infected wounds of the armed forces. Since that time, many lives have been saved by this so-called "miracle drug." Fleming and Florey shared the Nobel Prize for medicine in 1945 for their discovery.

Jonas Salk and the Polio Vaccine

In 1921, while vacationing on the Island of Campobello off the coast of Maine in New Brunswick (Canada), Franklin D. Roosevelt was stricken by paralytic polio and was crippled for life. In 1926, he established the nonprofit Warm Springs (Georgia) Foundation for treating polio victims. The March of Dimes program, which was associated with the foundation, amassed over $500 million to help polio victims, designating some $40 million to finance polio research. In this research endeavor, the conflict of heresy and established belief developed, yet both produced results. The heretic was Jonas Salk. His heresy was the use of a killed-virus vaccine.  In 1908, Karl Landsteiner (Austria) established that polio was caused by virus. By 1941, there were three general types of polio virus had been identified; it had also been determined that all strains of one type would immunize against strains of that type only. By 1952, it was known that polio virus circulated in the blood, and this fact proved to be its Achilles heel since a vaccine-produced antibody in the blood could protect against polio. Isabel Mountain prepared a killed vaccine using formaldehyde to inactivate the virus. She discovered that the killed-virus vaccine would produce a degree of immunity in a monkey without harm.

Given these bits and pieces, what was Jonas Salk’s claim to fame? Salk put all the pieces needed for eradication of the disease together by acting quickly and with great precision. In 1947, Salk, then 33, was Research Professor of Bacteriology and Pathology at the University of Pittsburgh. He undertook a program of typing the approximately one hundred strains of polio virus that had been isolated. He became bored during the latter part of the three-year program and began to look ahead to develop a vaccine based on the knowledge available to him. The typing program confirmed that their were only three types of polio virus. In 1951, Salk made a killed-virus vaccine—by treating polio viruses with formaldehyde at 36 °C for 11–13 days. This killed-virus vaccine produced a high degree of immunity to all three types of polio in monkeys contrary to the belief at the time that a killed-virus vaccine could not mobilize antibodies. Salk continued to run tests to ensure that his vaccine was safe by repeatedly determining that the vaccine contained no live virus. He tested his vaccine in immune children (who had had a previous paralytic infection of polio). In all cases some increase in antibody production was noted. In 1953, confident of his vaccine, Salk tested himself, his family and about 400 volunteers in Pittsburgh. One year later the vaccinated subjects were retested and found to have the same high level of vaccine-induced antibodies. Children were vaccinated before the polio seasons of 1954 and 1955. The test showed the vaccine to be safe and effective.

The medical establishment, led by Albert Sabin, complained about the use of the killed-virus vaccine. Sabin claimed that if live virus remained in the vaccine and it were used, it would kill and cripple. Sabin and his colleagues felt that use of a weakened live-virus vaccine was preferable. Throughout his preparation of the killed-virus vaccine,Salk made every effort to ensure that no live virus was present. Yet unintentionally, Salk hurt many feelings and stepped on many tender toes in the process. The ill will of the scientific community hurt Salk deeply, and he retreated into the seclusion of his laboratory at a time when the public wanted to give him a tickertape parade.

In 1955, a commercial laboratory carelessly produced and sold batches of Salk vaccine containing unkilled viruses. The defective vaccine caused 204 polio cases with 11deaths and over 100 cases of paralysis. Albert Sabin and the establishment rallied with an attack of vigor and by 1956, the medical establishment had produced a weakened, live virus vaccine (the Sabin vaccine). In 1964, the Surgeon General stated there was only a small risk involved with the Sabin vaccine. He failed to mention that with the killed Salk vaccine, properly prepared, there was no risk at all. The Salk vaccine became passé. Today, the Sabin vaccine is preferred by physicians.

Words about the concepts in this module can be obtained from the clues given. Find these words in the block of letters:

1. Substance that reacts with excess stomach acid.
2. Common name for a substance that changes a physical or psychological function in the body.
3. Need of increasing amounts of a substance to experience the same initial effects.
4. Acetaminophen, ibuprofen, or acetylsalicylic acid, for example.
5. Benzoyl peroxide is the active antiseptic ingredient in ____ ointments.
6. These organic compounds are required in small amounts in the diet.
7. Stimulant in cola and coffee.
8. Birth control drugs belong to this class of organic compounds.
9. The amount of this drug is determined in the Breathalyzer test.
10. Anabolic steroids are synthetic derivatives of this natural compound.

Answers:

2. ANTACID
3. DRUG
4. TOLERANCE
5. ANALGESIC
6. ACNE
7. VITAMINS
8. CAFFEINE
9. STEROIDS
10. ETHANOL
11. TESTOSTERONE

    2. See cartoons at end of module.

                    a. For the Apple II computer running on ProDOS: AR 702

b. For the Apple II computer: AP 701

3. Videodisc published by JCE: Software, a publication of the Journal of Chemical Education, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1396: (608) 262-5153 (voice) or (608) 262-0381 (FAX).