Part Two: Pharmaceutical Drugs, What Is Pharmaceutical Drugs?

Drug Pricing

In many jurisdictions drug prices are regulated. For example, in the UK the Pharmaceutical Price
Regulation Scheme is intended to ensure that the National Health Service is able to purchase drugs
at “reasonable prices.” In Canada, the Patented Medicine Prices Review Board examines drug pricing,

compares the proposed Canadian price to that of seven other countries and determines if a price is
“excessive” or not. In these circumstances, drug manufacturers must
submit a proposed price to the appropriate regulatory agency. In other jurisdictions, such as the
United States, drug costs are unregulated.

Blockbuster drug

A blockbuster drug is a drug generating more than $1 billion of revenue for the pharmaceutical company
that sells it each year. Cimetidine was the first drug ever to reach more than $1 billion a year in sales,
thus making it the first blockbuster drug.

Prescription drug history

Antibiotics first arrived on the medical scene in 1932; coined the "wonder drugs." The introduction of the
sulfa drugs led to a decline in the U.S. mortality rate from pneumonia to drop from 0.2% each year
to 0.05% by 1939. Antibiotics inhibit the growth or the metabolic activities of bacteria and other micro
organisms by a chemical substance of microbial origin.

Penicillin, introduced a few years later, provided a broader spectrum of activity compared to sulfa
drugs and reduced side effects. Streptomycin found in 1942, proved to be the first drug effective against
the cause of tuberculosis and also came to be the best known of a long series of important antibiotics.
A second generation of antibiotics were introduced in the 1940s: aureomycin and chloramphenicol.
Aureomycin was the best known of the second generation.

Lithium was discovered in the 19th century for nervous disorders and its possible mood-stabilizing or
prophylactic effect; it was cheap and easily produced. As lithium fell out of favor in France, valpromide
came into play. This antibiotic was the origin of the drug that eventually created the mood stabilizer category.

Valpromide had distinct psychotrophic effects that were of benfit in the treatment of both acute manic states
and in the maintenance treatment of manic depression illness.

Psychotropics can either be sedative or stimulant

Sedatives aim at damping down the extremes of behavior. Stimulants aim at restoring normality by
increasing tone. Soon rose the notion of a tranquilizer which was quite different from

any sedative or stimulant. The term tranquilizer took over the notions of sedatives and became the
dominant term in the West through the 1980s. In Japan, during this time, the term tranquilizer produced the
notion of a psyche-stabilizer and the term mood stabilizer vanished.

Premarin (conjugated estrogens, introduced in 1942) and Prempro
(a combination estrogen-progestin pill, introduced in 1995) dominated the hormone replacement therapy (HRT)
during the 1990s. HRT is not a life-saving medication, nor does it
cure any disease. HRT has been prescribed to improve one's quality of life.

Doctors prescribe estrogen for their older female patients both to treat short-term menopausal symptoms and to
prevent long term diseases.

In the 1960s and early 1970s more and more physicians began to prescribe
estrogen for their female patients. between 1991 to 1999, Premarin was listed as the most popular
prescription and best selling drug in America.

The first oral contraceptive, Enovid, was approved by FDA in 1960. Oral contraceptives inhibit ovulation and so
prevent conception. Enovid was known to be much more effective than alternatives including the condom and
the diaphragm. As early as 1960, oral contraceptives were available in several different strengths by every manufacturer.
In the 1980s and 1990s an increasing number of options arose including, most recently, a new delivery system for
the oral contraceptive via a transdermal patch. In 1982, a new version of the

Pill was introduced, known as the "biphasic" pill. By 1985, a new triphasic pill was approved.
Physicians began to think of the Pill as an excellent means of birth control for young women.

Stimulants such as Ritalin (methylphenidate)came to be pervasive tools for behavior management and modification
in young children. Ritalin was first marketed in 1955 for narcolepsy; it's potential users were middle-aged and the elderly.
It wasn't until some time in the 1980s along with hyperactivity in children that Ritalin came onto the market.
Medical use of methlyphanidate is predominately for symptoms of Attention

Deficit/Hyperactivity Disorder (ADHD). Consumption of methylphenidate in the U.S. outpaces all other countries
between 1991 and 1999. Significant growth in consumption was also evident in
Canada, New Zealand, Australia, and Norway. Currently, 85% of the world's methylphanidate is consumed in America.

The first minor tranquilizer was Meprobamate. Only fourteen months after it was made available, meprobamate had
already become the country's largest-selling prescription drug.
By 1957, meprobamate had become the fastest-growing drug in history.
The popularity of meprobamate paved the way for

Librium and Valium, two minor tranquilizers that belonged to a new chemical class of drugs called the benzodiazepines.
These were drugs that worked chiefly as anti anxiety agents and muscle relaxants.

The first benzodiazepine was Librium.
Three months after it was approved, Librium had become the most prescribed tranquilizer in the nation.

Three years later Valium hit the shelves and was ten times more effective as a muscle relaxant and anticonvulsant.
Valium was the most versatile of the minor tranquilizers. Later came the wide spread adoption of major tranquilizers

such as chlorpromazine and the drug reserpine. In 1970 sales began to decline for Valium and Librium; but sales of
new and improved tranquilizers, such as Xanax, introduced in 1981 for the newly created diagnosis of panic disorder soared.

Mevacor (lovastatin) is the first and most influential statin in the American market. The 1991 launch of Pravachol (pravastatin),
the second available in the United States, and the release of Zocor (simvastatin) made Mevacor no longer the only
statin on the market. In 1998 Viagra was released as a treatment for erectile dysfunction.

Ancient pharmacology

Using plants and plant substances to treat all kinds of diseases and medical conditions is believed to date back to
prehistoric medicine.

The Kahun Gynaecological Papyrus, the oldest known medical text of any kind, dates to about 1800 BC and represents
the first documented use of any kind of medication.
It and other medical papyri describe Ancient Egyptian medical practices, such as using honey to treat infections.

Ancient Babylonian medicine demonstrate the use of prescriptions in the first half of the 2nd millennium BC.
Medicinal creams and pills were employed as treatments.
On the Indian subcontinent, the Atharvaveda, a sacred text of Hinduism whose core dates from the 2nd millennium BC,
although the hymns recorded in it are believed to be older, is the
first Indic text dealing with medicine. It describes plant-based medications to counter diseases.

The earliest foundations of ayurveda were built on a synthesis of selected ancient herbal practices, together with a
massive addition of theoretical conceptualizations, new nosologies and new therapies dating from about 400 BC onwards.

The student of Ayurveda was expected to know ten arts that were indispensable in the preparation and application of
his medicines: distillation, operative skills, cooking, horticulture,
metallurgy, sugar manufacture, pharmacy, analysis and separation of minerals, compounding of metals, and preparation
of alkalis.

The Hippocratic Oath for physicians, attributed to 5th century BC Greece, refers to the existence of "deadly drugs", and
ancient Greek physicians imported medications from Egypt and elsewhere.

Medieval pharmacology

Al-Kindi's 9th century AD book, De Gradibus and Ibn Sina (Avicenna)'s The Canon of Medicine cover a range of drugs
known to Medicine in the medieval Islamic world.

Medieval medicine saw advances in surgery, but few truly effective drugs existed, beyond opium and quinine.
Folklore cures and potentially poisonous metal-based compounds were popular treatments.

Theodoric Borgognoni, (1205-1296), one of the most significant surgeons of the medieval period, responsible for
introducing and promoting important surgical advances including basic antiseptic
practice and the use of anaesthetics. Garcia de Orta described some herbal treatments that were used.

Modern Pharmacology

For most of the 19th century, drugs were not highly effective, leading Oliver Wendell Holmes, Sr. to famously comment in
1842 that "if all medicines in the world were thrown into the sea, it would be all the better for mankind and all the worse
for the fishes".

During the First World War, Alexis Carrel and Henry Dakin developed the Carrel-Dakin method of treating wounds
with an irrigation, Dakin's solution, a germicide which helped prevent gangrene.

In the inter-war period, the first anti-bacterial agents such as the sulpha antibiotics were developed.
The Second World War saw the introduction of widespread and effective antimicrobial therapy with the
development and mass production of penicillin antibiotics, made possible by the pressures of the war and the
collaboration of British scientists with the American pharmaceutical industry.

Medicines commonly used by the late 1920s included aspirin, codeine, and morphine for pain; digitalis, nitroglycerin,
and quinine for heart disorders, and insulin for diabetes.

Other drugs included antitoxins, a few biological vaccines, and a few synthetic drugs. In the 1930s antibiotics emerged:
first sulfa drugs, then penicillin and other antibiotics.
Drugs increasingly became "the center of medical practice".

In the 1950s other drugs emerged including corticosteroids for inflammation, rauwolfia alkaloids as tranqulizers and
antihypertensives, antihistamines for nasal allergies,
xanthines for asthma, and typical antipsychotics for psychosis.
As of 2007, thousands of approved
drugs have been developed. Increasingly, biotechnology is used to discover biopharmaceuticals.

Recently, multi-disciplinary approaches have yielded a wealth of new data on the development of novel antibiotics and
antibacterials and on the use of biological agents for antibacterial therapy.

In the 1950s new psychiatric drugs, notably the antipsychotic chlorpromazine, were designed in laboratories and
slowly came into preferred use.

Although often accepted as an advance in some ways, there was some opposition, due to serious adverse effects
such as tardive dyskinesia.
Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control.

Governments have been heavily involved in the regulation of drug development and drug sales. In the U.S., the
Elixir Sulfanilamide disaster led to the establishment of the Food and Drug Administration, and the 1938 Federal Food,
Drug, and Cosmetic Act required manufacturers to file new drugs with the FDA.

The 1951 Humphrey-Durham Amendment required certain drugs to be sold by prescription. In 1962 a subsequent
amendment required new drugs to be tested for efficacy and safety in clinical trials.

Until the 1970s, drug prices were not a major concern for doctors and patients. As more drugs became prescribed
for chronic illnesses, however, costs became burdensome, and by the
1970s nearly every U.S. state required or encouraged the substitution of generic drugs for higher-priced brand names.
This also led to the 2006 U.S. law, Medicare Part D, which offers Medicare coverage for drugs.

As of 2008, the United States is the leader in medical research, including pharmaceutical development. U.S. drug prices
are among the highest in the world, and drug innovation is correspondingly high. In 2000 U.S. based firms developed
29 of the 75 top-selling drugs; firms from the second-largest market, Japan, developed eight, and the

United Kingdom contributed 10. France, which imposes price controls, developed three. Throughout the 1990s outcomes
were similar.

Controversies

Controversies concerning pharmaceutical drugs include patient access to medications under development and not yet
approved, drug pricing, and environmental issues.

Access to unapproved drugs

Governments worldwide have created provisions for granting access to drugs prior to approval for patients who have
exhausted all alternative treatment options and do not match clinical trial entry criteria. Often grouped under the labels of
compassionate use, expanded access, or named patient supply, these programs are governed by
rules which vary by country defining access criteria, data collection, promotion, and control of drug distribution.

Within the United States, pre-approval demand is generally met through treatment IND (investigational new drug)
applications (INDs), or single-patient INDs. These mechanisms, which fall under the label of expanded access programs,
provide access to drugs for groups of patients or individuals residing in the US.

Outside the US, Named Patient Programs provide controlled, pre-approval access to drugs in response to requests
by physicians on behalf of specific, or “named”, patients before those medicines are licensed in the patient’s home country.

Through these programs, patients are able to access drugs in late-stage clinical trials or
approved in other countries for a genuine, unmet medical need, before those drugs have been licensed in the
patient’s home country.

Patients who have not been able to get access to drugs in development have organized and advocated for
greater access. In the United States, ACT UP formed in the 1980s, and eventually formed its Treatment Action Group
in part to pressure the US government to put more resources into discovering treatments for AIDS and then to
speed release of drugs that were under development.

The Abigail Alliance was established in November 2001 by Frank Burroughs in memory of his daughter, Abigail.
The Alliance seeks broader availability of investigational drugs on behalf of terminally ill patients.

In 2013, BioMarin Pharmaceutical was at the center of a high profile debate regarding expanded access of cancer
patients to experimental drugs.

Access to medicines and drug pricing

Essential medicines as defined by the World Health Organization (WHO) are "those drugs that satisfy the health care
needs of the majority of the population; they should therefore be available at all times in adequate amounts and in
appropriate dosage forms, at a price the community can afford.

Recent studies have found that most of the medicines on the WHO essential medicines list, outside of the field
of HIV drugs, are not patented in the developing world, and that lack of widespread access to these medicines arise
from issues fundamental to economic development - lack of infrastructure and poverty.

Medecins Sans Frontieres also runs a Campaign for Access to Essential Medicines campaign, which includes
advocacy for greater resources to be devoted to currently untreatable diseases that primarily occur in the developing world.
The Access to Medicine Index tracks how well pharmaceutical companies make their products available in the developing
world.

World Trade Organization negotiations in the 1990s, including the TRIPS Agreement and the Doha Declaration, have
centered on issues at the intersection of international trade in pharmaceuticals and intellectual property rights, with
developed world nations seeking strong intellectual property rights to protect investments made to develop

new drugs, and developing world nations seeking to promote their generic pharmaceuticals industries and their ability to
make medicine available to their people via compulsory licenses.

Some have raised ethical objections specifically with respect to pharmaceutical patents and the high prices for medication
that they enable their proprietors to charge, which poor people in the developed world, and developing world, cannot afford.

Critics also question the rationale that exclusive patent rights and the resulting high prices are required for
pharmaceutical companies to recoup the large investments needed for research and development.

One study concluded that marketing expenditures for new drugs often doubled the amount that was allocated for
research and development.

Other critics claim that patents reward and abet misplaced pharmaceutical R&D priorities, which they describe as
being directed to creating incremental improved treatments for diseases prevalent in wealthy countries and away from
diseases that cause devastation in the developing world.

Novartis fought a protracted battle with the government of India over the patenting of its drug, Gleevec, in India, which
ended up in India's Supreme Court in a case known as Novartis v. Union of India & Others. The Supreme
Court ruled narrowly against Novartis, but opponents of patenting drugs claimed it as a major victory.

Environmental issues

The environmental impact of pharmaceuticals and personal care products is controversial . PPCPs are
substances used by individuals for personal health or cosmetic reasons and the products used by agribusiness to

boost growth or health of livestock. PPCPs have been detected in water bodies throughout the world and ones that
persist in the environment are called Environmental Persistent Pharmaceutical Pollutants. The effects of these

chemicals on humans and the environment are not yet known, but to date there is no scientific evidence that they have
an impact on human health.