Transcript 1. dia - Budapest University of Technology and Economics

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
Prontosil
Streptococcus
bacteria
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
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
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 betablockers and potassium or calcium channel
antagonists.
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.
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).
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
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.
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.
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
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
III.9. Novel Healthcare 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 germfree 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.
III.9. Novel Healthcare 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.