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HISTORICAL
THERAPEUTIC USES OF ARSENIC
Arsenic is used as a healing
agent after Greek physicians
Hippocrates and
Galen popularize use.
Arsenic solutions came in tablets, pastes, and
later, injectable forms.
Victorian Era
Arsenic is an active ingredient in
popular medicines.
Arsenic poisoning mimicked diseases like
cholera and
dysentery.
"The infiltration of arsenic into 19th-century domestic life
was the template for pollution in the modern industrial world. One of the most
disturbing discoveries in my research was how cavalier candy-makers were in
using poison to increase their profits." - James C. Whorton, The Arsenic
Century
Arsenic is used in wallpaper,
beer, wine, sweets,
cosmetics, wrapping paper, painted toys, sheep dip, insecticides, clothing,
dead bodies, stuffed animals, hat ornaments and candles.
Green
wallpaper had larger quantities of the copper(II) acetoarsenite.
Arsenic
affects individuals differently depending on age and diet protein.
Members of a household can be stricken with illness while others may
not.
People knew arsenic was poisonous thinking only ingestion caused
illness.
But products with arsenic can off-gas arsenic into the air.
Small amounts of arsenic deadly to children and elderly are easily
metabolized by healthy adults, the reason it took so long to ban arsenic
wallpaper.
Chronic arsenic poisoning became common among high society.
In melodramas, "going into the green room" was tantamount to falling
sick.
"White arsenic (arsenious oxide) was the poisoner's first choice
owing to its easy accessibility and its mimicry of the gastrointestinal illnesses of the
day, including cholera.
Poverty-stricken parents used arsenic to rid
themselves of excess children; wives used it against husbands and husbands
against wives; children used it against parents.
The new life-insurance
industry added to the temptation: one woman, Mary Ann Cotton, murdered her
mother, three husbands, a fiancé, and many of her 15 children and
stepchildren for insurance payouts." - Michal Meyer
Arsenic ubiquity
left Victorian murderers
and murderesses with ample alibis.
1851 Napoleon Bonaparte dies
of arsenic posioning.
Fowler's Solution
1% arsenic trioxide preparation, was widely used during the 19th
century.
British Pharmaceutical and Therapeutic Products lists
Fowler's solution as used for: leukaemia, skin conditions (psoriasis,
dermatitis herpetiformis, and eczema), stomatitis and gingivitis in infants,
and Vincent's angina.
Fowler's solution was also prescribed as a health
tonic.
Chronic arsenic intoxication from long term use of Fowler's
solution caused haemangiosarcoma, liver angiosarcoma and nasopharyngeal
carcinoma.
Arsenic is the
primary treatment for
syphilis until World War II.
Arsphenamine (neoarsphenamine), a 30%
arsenic light yellow compound was used intravenously to treat
syphilis, yaws, and protozoan
infections.
Paris Green
Copper(II)
acetate triarsenite or copper(II) acetoarsenite.
A highly toxic
inorganic emerald-green crystalline powder used as a rodenticide and
insecticide, and also as a pigment, despite its toxicity.
It is also
used as a blue colorant for fireworks.
The color of Paris Green is said
to range from a pale blue green when very finely ground, to a deeper green when
coarsely ground.
At the turn of the 20th century, Paris Green, blended
with lead arsenate, is used in America and elsewhere as an insecticide on
produce such as apples.
Paris Green is said "to have burned the trees
and grass around the trees".
CURRENT THERAPEUTIC USES OF
ARSENIC
Arsenic
trioxide (As2O3) is now widely used to induce remission in patients with
acute promyelocytic leukaemia, based on
its mechanism as an inducer of apoptosis (programmed cell death).
Arsenic induces apoptosis by releasing an apoptosis-inducing factor
(AIF) from the mitochondrial intermembrane space from where it translocates to
the cell nucleus.
AIF then effects apoptosis, resulting in altered
nuclear biochemistry, chromatin condensation, DNA fragmentation, and cell
death.
AIF is a isolated, cloned flavoprotein with a molecular weight
of 57,000.
57,000-mol-wt protein uniquely
present in nonproliferating cells and senescent human
fibroblasts
The flavoprotein family contains a diverse range of
enzymes, including:
Adrenodoxin reductase involved
in steroid hormone synthesis in
vertebrates;
Epidermin biosynthesis, EpiD, shown to be a flavoprotein
that binds FMN;
The B chain of dipicolinate synthase, an enzyme which
catalyses the formation of dipicolinic acid from dihydroxydipicolinic
acid;
Phenylacrylic acid decarboxylase EC 4.1.1. - a resistance enzyme
to cinnamic acid.
ACUTE ARSENIC
POISONING
Diarrhea attributed to increased permeability of the blood
vessels is a dominant feature.
Encephalopathy is
a common manifestation and
the possibility of
arsenic toxicity
must be considered if the aetiology of encephalopathy is uncertain.
The neurological effects are
many and varied.
The most frequent finding is a
peripheral neuropathy mimicking
Guillain-Barré
syndrome with similar electromyographic findings.
2015
Phosphate
fertilizer source of arsenic in chronic kidney disease in Sri
Lanka
A massive federal study, the $18-million Women's Health
Initiative published in the New England Journal of
Medicine, showed that calcium supplements made no significant
difference in woman's bone density and did not significantly reduce bone
fractures.
Eric T. Poehlman built a reputation as one of the leading
authorities on the metabolic changes that come with aging, particularly during
menopause; he published more than 200 journal articles over two decades of
research.
Eric T. Poehlman publish utterly fraudulent research alleging
hormone replacement injections as a therapy for menopause falsifying 17 grant
applications to the National Institutes of
Health and fabricating data in 10 of his papers that were submitted
between 1992 and 2000.
Eric T. Poehlman plead guilty to civil, criminal
and administrative charges.
An earlier Women's Health Initiative
study showed hormone treatment after menopause conferred more risks than
benefits.
2007 State court jury in
Philadelphia found
Wyeth "malicious, wanton, willful or
oppressive" in the manufacturing, marketing and sales of Prempro® menopause
pill.
Mary Daniel, after using the hormone therapy pill, contracted
breast cancer.
Wyeth paid ghostwriters to produce
medical journal articles favorable to its female hormone replacement therapy
Prempro®.
As early as 1997,
Wyeth paid the medical writing
firm DesignWrite to publish favorable journal articles about Prempro® under
academics' names.
Around 5000 lawsuits wait to be heard over the hormone
therapies Prempro® and Premarin®.
"Newly unveiled court
documents show that ghostwriters paid by a pharmaceutical corporation played a
major role in producing 26 scientific papers backing the use of hormone
replacement therapy in women.
The articles, published in medical
journals between 1998 and 2005, emphasized the benefits and de-emphasized the
risks of taking hormones" - Natasha Singer, August 4, 2009
The
Council on Hormone Education sponsors a University of Wisconsin-Madison
online course entirely funded by a $12 million grant from
Wyeth.
Thirty-four
of the 40 Council on Hormone Education member physicians have financial
ties to Wyeth.
Medical professionals without ties to
Wyeth called the course
materials "not good
science" and "pure,
undisguised marketing."
"David B.
Morris argues convincingly that our culture has embraced a "myth of the two
pains": belief mental and physical pain are totally different phenomena.
Common sense and science tell us that they, in fact, can not be
separated.
Pain, Morris writes, "is far more than simply or exclusively
a medical problem.
It can not be reduced to a mere transaction of the
nervous system but also shaped by such powerful cultural forces as gender,
religion and social class."
Consider the medieval Catholic
self-flagellator, the Iroquois warrior who defined his identity by his defiance
of torture, the American evasion of the discomfort.
A culture's
response to pain can tell us a great deal.
A corporate or individual's
attitude toward pain can be revealing also.
Placing control of pain in
the hands of medical experts, making a sharp distinction between "mental" and
"physical" pain, using pain to fuel a profit-producing machine: these
contributed to the invention of heroin
as they did to aspirin."
The Birth of Heroin and the Demonization of
the Dope Fiend, Thomas A. Metzger |
"It has
been estimated conservatively that 16,500 NSAID-related deaths occur among
patients with rheumatoid arthritis or
osteoarthritis every year in the US.
This figure is similar to the number of
deaths from the acquired immunodeficiency
syndrome and considerably greater than the number of
deaths
from multiple myeloma,
asthma,
cervical cancer, or Hodgkin's
disease." - J.S. Hochman, M.D., Executive Director of the National
Foundation for the Treatment of Pain 2003
Non-steroidal anti-inflammatory
drugs, usually abbreviated to NSAIDs, are drugs with
analgesic, antipyretic and
anti-inflammatory effects - they reduce pain,
fever and inflammation.
More than 100,000 people are hospitalized each year because of adverse
reactions to NSAIDs.
More than 15,000 people die, often because of
compliciations caused by bleeding or perforated ulcers.
Drugs in this
class include ibuprofen (Advil®, Motrin®), diclofenac (Cataflam®,
Voltaren®), meloxicam (Mobic®), naproxen (Aleve®, Naprosyn®)
and indomethacin (Indocin®).
In addition to
digestive-tract
damage, NSAIDs can raise blood
pressure and increase the risk of
heart attack and
stroke, as well as injure
kidneys and the
liver.
NSAIDs and
opiates can cause severe hypersensitivity reactions by their
cyclooxygenase-inhibiting mechanism or by direct effects on mast cells.
It is possible some cases in these groups are pseudoallergic or
IgE-independent anaphylactic reactions, rather than IgE-mediated anaphylactic
reactions.
NSAIDs were the most frequent culprits in
drug induced anaphylaxis
(47.9% of cases), followed by
antibiotics
(35.5%) and anaesthetic agents (6.1%)
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