Transcript Medicinea4

III. TECHNOLOGY MILESTONES IN HEALTH AND MEDICINE
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. The first sulfa drug, Prontosil, 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 of 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 Prontosil was later
discovered to be sulphanilamide. Many other antibiotics were
then created from this agent, including Sulphapyridine in 1938.
The sulfa drugs were dramatically successful in reducing the
mortality rate of lobar pneumonia in the 1940s, and saved the
lives of millions. Their importance declined only with the advent of
the Penicillin era.
Alexander
Fleming
Penicillium notatum
Gerhard Domagk
Streptococcus
bacteria
Prontosil
Penicillin
In 1928, the Scottish bacteriologist, Alexander Fleming, discovered
a potent substance that could kill bacteria, which he isolated from a
naturally occurring mold (Penicillium notatum). 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 in 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. Their success
heralded the beginning of the modern era of antibiotic therapy.
Zidovudine (AZT)
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
HIV’s drug resistance, first demonstrated with AZT,
mono-drug therapy can no longer be used to treat
HIV infection.
Zidovudine crystals
Zidovudine
III. TECHNOLOGY MILESTONES IN HEALTH AND MEDICINE
III.7. Cardiovascular Management
Regulating heart beat
The ability of the local anesthetic Procaine to regulate the heart
beat (also called anti-arrhythmic activity) was discovered in the
1930s. This type of pharmaceutical treatment is complex and can
be quite difficult because the 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. Procaine inhibits the cell membrane proteins known as
sodium channels. Procaine was followed by numerous drugs,
including beta-blockers and potassium or calcium channel
antagonists.
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 was extracted from the
leaves of grecian foxglove (Digitalis lanata)
and approved in 1954 to treat atrial fibrillation
and congestive heart failure. It was eventually
discovered that anti-hypertensive drugs can
also be used to treat heart failure.
Busting blood clots
Heparin, a natural product isolated from animal livers, was first
used to precent 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 during 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 even 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).
Arterioschlerosis
Controlling blood cholesterol levels
The buildup of cholesterol deposits inside arteries (arteriosclerosis) is a major
cause of coronary heart disease and strokes. Lovastatin (Mevacor) which
controls blood cholesterol levels (hypolipemic activity) by inhibiting a critical
enzyme from being converted into mevalonate, an early and rate-limiting step
in cholesterol biosynthesis, was approved in 1987. Subsequent and more
potent drugs, such as Simvastatin and Atorvastatin, have revolutionized the
treatment of high level of lipids in the blood (hyperlipidemia) by being highly
effective and well tolerated.