III.6. Anti-infective Drugs

1. III.6. Anti-infective Drugs Salvarsan and Prontosil Paul Ehrlich, the German bacteriologist, studied arsenic compounds for their anti-bacterial properties and invented Salvarsan in 1909, as a successful treatment for the fatal, sexually transmitted disease, syphilis. This strategy was followed by other researchers to find active compounds for combating infectious diseases. Prontosil, the first sulfa drug, which was formerly used as a textile dye, was discovered in 1932 as chemists searched for an antibacterial drug that could cure the deadly streptococcal infection, a common cause for chronic pneumonia. This discovery was so important that the German biochemist Gerhard Domagk received the 1939 Nobel Prize in medicine for his work in this area. The active antibacterial agent of Prfontosil was later discovered to be sulphanilamide Many other antibiotics werethen created from this agent, including sulphapyridine (1938). The sulfa drugs were dramatically successful in reducing the mortality rate of lobar pneumonia in the 1940s, and saved the lives of millions . The importance declined only with the advent of the Penicillin era. Paul Ehrlich, the inventor of Salvarsan Gerhard Domagk Streptococcus bacteria Prontosil

2. III.6. Anti-infective Drugs Penicillin In 1928, the Scottish bacteriologist Alexander Fleming discovered a potent substance that could kill bacteria, which he isolated from a naturally occurring mould (Penicillium notatum) by in 1928. Penicillin, a drug based on this natural substance, was created during a massive wartime project in 1943; it dramatically reduced infection and amputation among injured soldiers of the American and British armies throughout World War II. This natural Penicillin was so expensive and rare, that it had to be recycled from the urine of the treated patients. Chemists attempted a new method of synthesis: to artificially manufacture the natural substance on which the drug was based. The chemical structure of penicillin was determined by the British researcher, Dorothy Crowfoot Hodgkin in the 1940s, enabling its synthesis. By 1957, several pharmaceutical companies synthesized and commercially produced this drug. This success heralded the beginning of the modern era of antibiotic therapy. Alexander Fleming

3. III.6. Anti-infective Drugs Zidovudine Zidovudine (AZT) was approved in the United States for the treatment of Human Immunodeficiency Virus (HIV) infection in 1987. This drug was first synthesized in 1964 but proved ineffective as a cancer chemotherapeutic. It was abandoned until 1986, when its activity against retroviruses was discovered by an American research group. AZT and related nucleoside drugs inhibit viral replication by targeting specific viral enzymes. Because of the rapid development of drug resistance first demonstrated with AZT, mono-drug therapy can no longer be used to treat HIV infection. Zidovudine crystals Zidovudine

4. III.7. Cardiovascular Management Regulating heart beat In the 1930s, the ability of the local anesthetic procaine to regulate the heart beat (also called anti-arrhythmic activity) was discovered. This type of pharmaceutical treatment is complex and can be quite difficult because drugs that block arrhythmia can also cause arrhythmia under certain conditions. Procaine was the first of many drugs that were eventually approved for this use. Procain inhibits the cell membrane proteins known as sodium channels. Procaine was followed by numerous drugs including beta-blockers and potassium or calcium channel antagonists.

5. III.7. Cardiovascular Management Treating heart failure Digitalis glycosides, a group of compounds that occur naturally in a number of plants, have been used to treat heart failure for centuries. After research identified how they increase the force with which the heart contracts, Digoxin (contains carbohydrates and no sugar components) was extracted from the leaves Digitalis lanata and was approved in 1954 to treat atrial fibrillation and congestive heart failure. It was eventually discovered that antihypertensive drugs can also be used to treat heart failure.

6. III.7. Cardiovascular Management Busting blood clots Heparin, a natural product isolated from animal livers, prevents thrombosis (blood clotting) during a blood transfusion in 1935 and soon became the most commonly-used anticoagulant (also called a blood thinner). It also prevents clot formation in cardiac and arterial surgery. Wafarin (Coumadin), an orally-active anticoagulant that prevents strokes and treats heart attacks and thrombosis was approved in 1955. During the 1970s, it was discovered that once clots have formed, they can be treated with thrombolytics. Utilizing enzyme activity to dissolve blood clots led to Urokinase (1977), streptokinase (1978), and the genetically engineered recombinant tissue plasminogen activator, tPA (1987).

7. III.7. Cardiovascular Management Controlling blood cholesterol levels The buildup of cholesterol deposits inside the arteries (arteriosclerosis) is a major cause of coronary heart disease and strokes. Lovastatin (Mevacor) controls blood cholesterol levels (hypolipemic activity) by inhibiting a critical enzyme being converted into mevalonate, an early and rate-limiting step in cholesterol biosynthesis was approved in 1955. Subsequent and more potent drugs, such as Simvastatin and Atorvastatin, have revolutionized the treatment of of high level lipids in the blood (hyperlipidemia) by being highly effective and well tolerated. Érelmeszesedés

8. III.8. Cancer Chemotherapy Evolution of cancer chemotherapy The use of chemicals to treat cancer (cancer chemotherapy) began in 1942 with the clinical use of nitrogen mustards by Louis S. Goodman and Alfred Gilman. Subsequent discoveries included mechlorethamine (Mustargen), chlorambucil (1952), and cyclophosphamide (1956). Drugs which block folic acid (also called antimetabolites) were also developed. Aminopterin (1947) was effective against leukemia, but its adverse effects on white blood cells quickly led to its replacement by methotrexate. In the 1950s, George Hitchings and Charles Heidelberger developed the antimetabolitic mercaptopurine for leukemia and Fluorouracil for gastrointestinal and breast tumors.

9. III.8. Cancer Chemotherapy Cytotoxic drugs Cytotoxic drugs (or drugs which are poisonous to cells) were isolated from plants and first introduced into cancer chemotherapy in 1963. These anti-cancer drugs work on the principle that rapidly proliferating cells, such as neoplastic (or cancerous) ones, are most susceptible to damage by cytotoxic drugs. Several variations include vinca alkaloids (vincristine and vinblastine) isolated from periwinkle plants and podaphylotoxin isolated from mayapple in 1970. Paclitaxel (Taxol) was isolated from the pacific yew in 1971 and developed to treat advanced breast cancer and lung cancer in the early 1990s.

10. III.8. Cancer Chemotherapy Tamoxifen Tamoxifen, a synthetic molecule, developed in 1971, was introduced in 1977 to treat breast cancer because it slows the growth of estrogen-dependent tumors. High estrogen levels promote the cell proliferation in breast tissue, so this type of chemotherapy blocks the natural hormones that can stimulate growth of cancer cells. Megestrol (Megace) is a synthetic derivative of the naturally occurring steroid hormone, progesterone, and functions in a similar manner and is used in the treatment of recurrent breast tumors. Personal monitoring of breasts promotes early diagnosis

11. III.9. Novel Healthcare Materials Artificial limbs and medical devices Modern artificial limbs and organs, replacement joints, contact lenses and hearing aids, and biomaterials which are crafted from specialized plastics and other high-tech materials have all been produced through chemistry. By manipulating the structures of molecules and creating new ones, chemists and engineers have developed new medical materials that are strong, flexible, and durable. A few such medical devices include the 1945 artificial kidney, the 1950s prosthetic heart valves, and the 1982 surgical implantation of a permanent artificial heart. Plastic contact lenses were introduced in 1956, and soft bifocal contacts were refined in 1985. Artificial heart valves Artificial heart

12. III.9. NovelHealthcare Materials Medical equipment Chemistry is used to manufacture nearly all of the plastic and vinyl medical devices used in today’s hospitals and health care clinics. Today’s medical equipment must be durable enough for daily use while helping to create clean, sterile, and germ-free environments. Many routine medical processes utilize state-of-the-art diagnostic equipment, stethoscopes, bandages and other novel fabrics, syringes, surgical instruments, blood bags, and plastic supplies that are produced through chemistry. Hygroscopic polymers that prevent inflammation of the sensitive skin of babies.

13. III.9. NovelHealthcare Materials Disinfectants and bleach Chemistry makes it possible to sanitize your home, breakdown mold and mildew, and to remove stains. In the early 1900s, chemists focused on controlling bacteria and cleaning clothes and home surfaces effectively. In 1913, researchers developed a formula for bleach that was affordable and easy to use. Today, bleach is a household commodity and an effective disinfectant which eliminates billions of germs and bacteria. Chlorine is also a powerful weapon against diseases caused by viruses and bacteria in homes, hospitals, and other buildings. Ignatius Semmelweis, the Hungarian gynecologist was first to introduce hand washing in chlorine water to his department in 1847.