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Medication: the story on HearLore | HearLore
Medication
Medication is a substance used to diagnose, cure, treat, or prevent disease, yet its history is a story of profound transformation from ancient herbal remedies to the complex chemical compounds of the modern era. The journey began thousands of years ago with the Kahun Gynaecological Papyrus, the oldest known medical text dating to about 1800 BC, which documented the use of honey to treat infections and the legs of bee-eaters to alleviate neck pain. These early practices laid the groundwork for what would become a global industry, evolving from the Atharvaveda in India, which described plant-based drugs to counter diseases, to the Hippocratic Oath in fifth century BC Greece, which referred to the existence of deadly drugs. The pharmacopoeia written by the Greek physician Pedanius Dioscorides between 50 and 70 CE remained widely read for more than 1,500 years, establishing a foundation of knowledge that would eventually lead to the development of antibiotics and other life-saving treatments. The transition from these ancient methods to modern pharmacology was not immediate; 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. This skepticism began to shift with the discovery of sulfa drugs in 1932 by Gerhard Domagk, which were coined the wonder drugs and led to a dramatic drop in pneumonia mortality rates in the United States from 0.2% to 0.05% by 1939. The subsequent introduction of penicillin a few years later provided a broader spectrum of activity and reduced side effects, marking the beginning of a new era in medical treatment. The development of antibiotics during the Second World War, made possible by the collaboration of British scientists with the American pharmaceutical industry, demonstrated the power of medication to save lives on a massive scale, setting the stage for the complex and expensive endeavors of drug discovery and development that continue today.
The Discovery Engine
The process of bringing a new drug to market is a lengthy, expensive, and inefficient journey that begins with drug discovery and culminates in clinical trials and regulatory approval. In 2010, the research and development cost of each new molecular entity was approximately US$1.8 billion, highlighting the immense financial burden placed on pharmaceutical companies, academic scientists, and governments. Drug discovery involves the identification of screening hits, medicinal chemistry, and optimization of those hits to increase affinity, selectivity, efficacy, metabolic stability, and oral bioavailability. Once a compound fulfills these requirements, it enters the process of drug development, which includes pre-clinical research on microorganisms and animals, followed by clinical trials on humans to confirm safety and efficacy. The final product of drug discovery is a patent on the potential drug, which requires very expensive Phase I, II, and III clinical trials, and most of them fail. Small companies often play a critical role by selling the rights to larger companies that have the resources to run the clinical trials. The process has evolved from serendipitous discovery and the identification of active ingredients from traditional remedies to the use of high throughput screening of large compound libraries against isolated biological targets. Modern drug discovery also involves the understanding of the shape of biological molecules at the atomic level to design drug candidates, a process known as drug design. Despite advances in technology and understanding of biological systems, the rate of new therapeutic discovery remains low, and the number of new blockbuster drugs approved by the government per billion dollars spent has halved every 9 years since 1950. This complex path from discovery to commercialization has made partnering a standard practice for advancing drug candidates through development pipelines, with governments regulating what drugs can be marketed, how they are marketed, and in some jurisdictions, drug pricing.
Common questions
What is the oldest known medical text that documented the use of medication?
The Kahun Gynaecological Papyrus is the oldest known medical text dating to about 1800 BC. It documented the use of honey to treat infections and the legs of bee-eaters to alleviate neck pain.
When did Gerhard Domagk discover sulfa drugs and what was the impact on pneumonia mortality rates?
Gerhard Domagk discovered sulfa drugs in 1932. This discovery led to a dramatic drop in pneumonia mortality rates in the United States from 0.2% to 0.05% by 1939.
Which drug was the first oral contraceptive and when was it approved by the FDA?
Enovid was the first oral contraceptive and it was approved by the FDA in 1960. It inhibited ovulation and proved much more effective than alternatives including the condom and the diaphragm.
How much did it cost to research and develop a new molecular entity in 2010?
In 2010, the research and development cost of each new molecular entity was approximately US$1.8 billion. This figure highlights the immense financial burden placed on pharmaceutical companies, academic scientists, and governments.
What is the primary avenue for medications reaching the environment?
The primary avenue for medications reaching the environment is through the effluent of wastewater treatment plants. These plants release chemical components from both industrial production and municipal consumption into lakes, rivers, and soil worldwide.
When did the Abigail Alliance establish its organization to seek broader availability of investigational drugs?
The Abigail Alliance was established in November 2001 by Frank Burroughs in memory of his daughter. The organization seeks broader availability of investigational drugs on behalf of terminally ill patients.
The history of medication is punctuated by the introduction of drugs that have fundamentally changed society, from the first oral contraceptive to the tranquilizers that defined an era of mental health treatment. The first oral contraceptive, Enovid, was approved by the FDA in 1960, inhibiting ovulation and proving much more effective than alternatives including the condom and the diaphragm. By 1985, a new triphasic pill was approved, and physicians began to think of the pill as an excellent means of birth control for young women. The development of stimulants such as Ritalin, first marketed in 1955 for narcolepsy, transformed behavior management in young children, with consumption in the United States outpacing all other countries between 1991 and 1999. The first minor tranquilizer, meprobamate, became the country's largest-selling prescription drug just fourteen months after it was made available, and by 1957, it had become the fastest-growing drug in history. This popularity paved the way for Librium and Valium, two minor tranquilizers that belonged to a new chemical class of drugs called the benzodiazepines. Librium became the most prescribed tranquilizer in the nation three months after it was approved, and Valium, introduced three years later, was ten times more effective as a muscle relaxant and anti-convulsant. The widespread adoption of major tranquilizers such as chlorpromazine and the drug reserpine followed, though these drugs were often met with opposition due to serious adverse effects such as tardive dyskinesia. The introduction of Viagra in 1998 as a treatment for erectile dysfunction and the dominance of hormone replacement therapy regimens like Premarin and Prempro during the 1990s further illustrate the profound impact of medication on daily life and medical practice. These drugs, from the pill to the tranquilizer, have shaped the way society views health, behavior, and the human body, creating a legacy that continues to influence modern medicine.
The Price of Progress
The economic landscape of medication is defined by the tension between innovation and accessibility, with drug prices often becoming a major concern for doctors and patients. In the United States, drug costs are partially unregulated, resulting from negotiations between drug companies and insurance companies, and high prices have been attributed to monopolies given to manufacturers by the government. The first blockbuster drug, Cimetidine, reached more than $1 billion a year in sales, setting a precedent for the financial success of pharmaceutical companies. However, the number of new blockbuster drugs approved by the government per billion dollars spent has halved every 9 years since 1950, raising questions about the efficiency of the drug development process. In the United Kingdom, the Pharmaceutical Price Regulation Scheme ensures that the National Health Service is able to purchase drugs at reasonable prices, with the payment percentage set by the scheme at 4.75% for 2017. Canada's Patented Medicine Prices Review Board examines drug pricing and determines if a price is excessive, comparing the National Average Transaction Price of patented drug products to those in France, Germany, Italy, Sweden, Switzerland, the United Kingdom, and the United States. Brazil has regulated drug prices through legislation under the name of Medicamento Genérico since 1999, while India's National Pharmaceutical Pricing Authority regulates drug prices. The controversy over drug pricing extends to the global stage, with World Trade Organization negotiations in the 1990s, including the TRIPS Agreement and the Doha Declaration, centering on issues at the intersection of international trade in pharmaceuticals and intellectual property rights. Critics argue that exclusive patent rights and the resulting high prices are required for pharmaceutical companies to recoup the large investments needed for research and development, while others claim that marketing expenditures for new drugs often double the amount allocated for research and development. The case of Novartis v. Union of India & Others, where the Supreme Court ruled narrowly against Novartis over the patenting of its drug Gleevec, highlights the ongoing struggle between intellectual property rights and the need for affordable access to essential medicines.
The Environmental Cost
The widespread use of medication has led to unintended consequences for the environment, with pharmaceutical medications described as ubiquitous in nearly every type of environmental medium. Their chemical components are typically present at relatively low concentrations in the ng/L to μg/L ranges, primarily reaching the environment through the effluent of wastewater treatment plants, both from industrial plants during production and from municipal plants after consumption. Agricultural pollution is another significant source derived from the prevalence of antibiotic use in livestock. Scientists generally divide environmental impacts of a chemical into three primary categories: persistence, bioaccumulation, and toxicity. Since medications are inherently bio-active, most are naturally degradable in the environment, however they are classified as pseudopersistent because they are constantly being replenished from their sources. These Environmentally Persistent Pharmaceutical Pollutants rarely reach toxic concentrations in the environment, however they have been known to bioaccumulate in some species. Their effects have been observed to compound gradually across food webs, rather than becoming acute, leading to their classification by the US Geological Survey as Ecological Disrupting Compounds. The presence of these pollutants in lakes, rivers, streams, estuaries, seawater, and soil worldwide raises concerns about the long-term impact on ecosystems and human health. The primary avenue for medications reaching the environment is through the effluent of wastewater treatment plants, which suggests that the very act of treating disease may contribute to environmental degradation. This paradox highlights the need for a more sustainable approach to drug development and disposal, ensuring that the benefits of medication do not come at the expense of the planet.
The Battle for Access
The fight for access to medication has become a central issue in global health, with governments and organizations working to ensure that essential medicines are available to those who need them. The World Health Organization defines essential medicines as those that satisfy the health care needs of the majority of the population, and they should 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, including lack of infrastructure and poverty. Médecins Sans Frontières runs a Campaign for Access to Essential Medicines, 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. In the United States, pre-approval demand is generally met through treatment IND applications, or single-patient INDs, which 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. Patients who have not been able to get access to drugs in development have organized and advocated for greater access, with groups like ACT UP forming in the 1980s to pressure the US government to put more resources into discovering treatments for AIDS and to speed the release of drugs that were under development. The Abigail Alliance, established in November 2001 by Frank Burroughs in memory of his daughter, seeks broader availability of investigational drugs on behalf of terminally ill patients. These efforts highlight the ongoing struggle to balance the need for innovation with the ethical imperative to provide access to life-saving treatments for all, regardless of their ability to pay.