Transcript hist2613.pharmacology

Potions & Poisons: Alchemy to Pharmacology
Definition: The Greek word for drug,
pharmakon means a drug, remedy, and a
poison. Drugs can be either toxins or antidotes.
General Points: Most therapies were
discovered by empirical means—observation,
accident, trial and error. The empirical
discovery of therapies depends on two
conditions: 1) what constitutes the disease; and
2) an opportunity to observe outcomes.
Origins: In the first century BC, King
Mithridates VI of Pontus in Asia Minor feared
that he was going to be murdered by the
Romans. He experimented by immunizing
against poisons by drinking the blood of ducks
who had been fed toxins—thus the universal
term for a universal antidote, mithridates.
Another ancient antidote was theriac, which
was developed to counteract animal poisons.
This term is from the Greek word therion (‘wild
beasts’), and there were a great variety of
recipes for this treatment, some involving up to
70 ingredients, including the flesh of vipers.
Both mithridates and theriac were used to treat
infectious diseases, conceived as ‘pests’ or
‘poisons’.
What is
Pharmacology?
Page from Early Modern
Text of Materia Medica, in
Latin
Doctors, or healers, have always used therapeutic
treatments. Ancient remedies included both magic
and prayer in addition to herbal treatments.
The usefulness of a spiritual factor is not limited to
the ancients, however, as pilgrims with a variety of
ailments continue to flock to healing shrines such
as Lourdes in France, Fatima in Portugal, and SteAnne-de-Beaupré in Quebec.
The spiritualistic or vitalistic aspect of treatment is a
an important element in the concept of a placebo
(from the Latin for ‘to please’). The term refers to
the administration of harmless but inert compounds
to treat a patient. However, before discounting the
placebo, clinical trials have demonstrated that they
are effective in virtually form of intervention against
almost all diseases.
Greek Therapeutics: In the Greco-Roman world
disease was thought to be caused by an imbalance
in the humours—thus treatment tried to restore the
balance. Key to treatment was the modification of
diet and lifestyle. Most Hippocratic treaties refer to
non-drug therapies such as bloodletting, special
diets, baths, exercise or rest, and applications of
heat or cold. However, more than 300 medications
are also cited—most of plant origin that were
applied either externally or internally. Hippocratic
doctors believed in the healing power of nature,
and that medicine was to help the body heal itself;
it was not supposed to hurt (although sometimes it
could). Primum non nocere (‘first, do no harm’)!
Faith & Placebos; and
Medicine in the Ancient
World
Pottery Votives Found in Greek
Healing Temples
Galen, in the second century AD was a
successful therapist. He utilized a wide
variety of medications, most of which
were vegetable derivatives, that came to
be known as galenicals, or simples.
Roman-era pharmacopoeia embraced the
therapies of much of the Classical age,
and relied on an assortment of medical
botany—more than 600 plants, animals
and their derivatives. Remedies were
classified by their physical qualities: oils,
animals, cereals, herbs, roots, and wines.
The most famous text was by
Dioscorides, a first-century Greek
physician, whose writing on materia
medica (‘medical substances’) was the
standard for more than 1,400 years.
Many of the herbal treatments first
discovered by the Greeks were ‘saved’ by
the Arab physicians in the early medieval
period, and then reintroduced to Europe
during the late Middle Ages where they
were they translated into Latin.
A problem for European physicians
consulting these works was that no
ancient illustrations survived, and most
descriptions of plants were difficult to
related to known species.
Therapeutics in
the Age of Galen
Early Modern Woodcut
Portrait of Galen
Medieval Pharmacology:
The Alchemists & Botany
In medieval Europe Churchmen, such as the
Venerable Bede (672-735) in England, and
fellow monks had extensive knowledge of
plant remedies. Unschooled healers often
used chants and charms to cure certain
diseases that they believed were caused by
bad luck, darts shot by elves, or evils of the
‘great worm’—a term applied to snakes,
insects and dragons.
Amulets, magic numbers, astrology, and
meteorological ‘research’ also demonstrated
the instability of much of society, how much
had been lost of past knowledge, and that the
torch of medicine had moved from Galen’s
Rome and Western Europe to the Arab empire
in the East.
One of the most famous botanical ingredients
was the mandrake root (mandragora) which
was used to make both love potions and as an
anesthetic—often mixed with wine. The
Mandrake’s anthropoid appearance led to the
development of a rich mythology that claimed
that humans who pulled it from the ground
would be killed by its screams (even in Harry
Potter), and that a dog should therefore be
tied to the root and tempted to harvest it by
placing a dish of meat nearby that the dog
would have to dig up.
Early Modern Alchemist’s
Workshop (Early 16th Century)
Medieval
Illustration
of the
Mandrake
Root
Metals and Therapeutics
While the ancient Greeks knew about
copper and did use it in some
treatments, it was not until the late
1400s that metals came to be widely
used in medical therapies. By the
Renaissance, the Greco-Roman
concept of the ‘earth’ element, had been
expanded to include the new elements
of salt, antimony, mercury and sulfur.
By the 16th century mercury was being
recommended as a treatment for the
new European disease of syphilis.
Mercury causes gastrointestinal
disturbances, gum swelling, salivation,
and neurological toxicity, but also was
an effective treatment for syphilis.
Antimony compounds produce nausea,
vomiting, purging and cardiovascular
collapse, but in a tartar emetic is was
one of the most popular therapies of the
early modern period (17th-18th
centuries), and despite calls for its
prohibition, was used as a ‘cure’ for
typhoid fever and pneumonia.
Medieval Couple in a Mercury Bath
A Canadian Story: Banting,
Best and Treating Diabetes
Frederick Banting (1891-1941), a physician in
London, Ontario, was convinced from his research
that a pancreatic disorder was the cause of
diabetes mellitus. In the summer of 1921, he
borrowed laboratory space from J.J.R. Macleod a
professor of physiology (who was away on a fishing
holiday in Scotland) at the University of Toronto to
work with Charles Best (a medical student) on
experimentally induced diabetes in dogs. They
isolated and purified the hormone insulin, using
extracts from the Islets of Langerhans in the
pancreas (along with J.B. Collip). They injected the
extract into a diabetic dog who was near death, but
who then made a rapid recovery. The result of this
work was that insulin was the first hormone to be
developed as a specific replacement therapy for
this common, and previously fatal disease. On 11
January 1922, they gave injections to a 14-year old
boy, Leonard Thompson, who was dying of
diabetes in the Toronto General Hospital.
Thompson’s blood-sugar level fell, and within days
he was out of bed, and in weeks returned home
where he could now live (albeit dependent on
insulin injections). The 1923 Nobel committee
presented the prize to Banting and Macleod, who
shared it with Best and Collip. The Eli Lilly
Company in Indianapolis, who had helped to solve
the technical problems with producing insulin, then
went into large-scale production of this life-saving
cure.
Frederick Banting and Charles
Best at University of Toronto
Frederick Banting (1891-1941)
Top Treatments Used or Sold in Various
Medical Practices, 1795-1930s
1795
1850s
1880s
1930s
Opium
Quinine
Cupping
Codeine
Blisters
Opium
Opium
Acetylsalicylic acid
Senna
Venesection
Tartar emetic
Sodium
bicarbonate
Aloes
Tartar emetic
Chloroform
Acetphenetidin
Tartar
Calomel (mercury)
Bromide
Elixir pepsin
Cinchona
Blisters
Aconite
Sodium bromide
Licorice
Ipecac
Chloral hydrate
Glycerin
Enemata
Cupping
Enemata
Sodium salicylate
Mercurials
Iron
Milk
Nux vomica
Jalap
Jalap
Ammonium
Clorate
A Pharmaceutical’s
Life Cycle: The Jawetz
Curve
The Jawetz model, first proposed in
the mid 1950s closely fits the history
of most new remedies: First, the use
rises quickly during a period of
optimism, then some side effect is
noted, and the approval drops rapidly
(based on fear and mistrust), and
then its use stabilizes at a moderate
level. These swings have been
called: “from panacea to poison to
pedestrian.”
While rigorous drug testing attempts
to eliminate the huge drops due to
unexpected side-effects, some dips
are the result of other factors such as
which disease is fashionable, and
who the target audience is.
While most used/sold drugs have
changed dramatically over the past
200 years, the problems they
were/are meant to treat is consistent:
heart disease, lung disease, stomach
ailments, mental disorders—in short
chronic problems, many of which are
related to diet and lifestyle. Were the
ancient Greeks therefore far off the
mark?
Ernest Jawetz
(b. 1916) [right]
Graph of
Phases in a
Drug’s Use
(Jawetz in Annual
Review of Medicine
(1954)) [below]