Module 5: The black death in Europe, Cholera in London, Opioids in America

A short take on a long history

Class of drugs that work on opioid receptors in the brain. Include drugs like heroin, fentanyl, morphine, and OxyContin. Opium poppy has been used since Hippocrates. In Ancient Rome the poppy was a symbol of sleep and death. A German pharmacist figured out how to isolate morphine from opium in the 19th century and it became commonly prescribed. In the early 20th century, it became a criminalized non-clinical offense to use opium recreationally. At the same time, a European chemist began to create semi-synthetic opioids, and later fully-synthetic opioids like Demerol or fentanyl. They were prescribed largely as a drug of last resort - for acute pain and to ease suffering of dying patients. This began to change in 1996.

Treating the Plague

Burning aromatic herbs in homes, bleeding patients to remove excess heat and affected humors and lanced their buboes for the same reasons. Galenic traditions - rubbing the backend of a live chicken against the freshly-lanced buboes in order to draw out the poison, and even drinking the fluids that came from the buboes.

Targeting Chronic Pain

Drug reps focus was to dismiss the idea of OxyContin being addictive and convincing physicians to consider OxyContin as a treatment for chronic pain. Before this, Opioids were still stigmatized by physicians and advised only for prescription of acute pain, usually following surgery and prescribed in low doses where addiction was less likely. This marketing campaign worked and OxyContin exploded all over the prescription pads beginning in the late 90s. Opioids began to be prescribed in high doses and for long periods of time to patients with back pain, arthritis, fibromyalgia, sports injuries, and many other things.

The black death strikes

Europe was overcrowded, and in Sicily in the year 1347 the bubonic plague hit. It slowly spread through Europe over the next few years, interrupting trade, agriculture, and city functions. By 1353, 30% to 60% of Europe's population had succumbed to the disease.

The Advent of OxyContin

In 1996, a small drug company came out with OxyContin, which was a time-released opioid containing Oxycodone. The FDA approved it and stated the drug was safer than rival painkillers because of its delated absorption. This made it unique on the market, and led physicians to believe it was safer than alternatives and virtually non-addictive. OxyContin was subject to one of the biggest marketing campaigns in pharmaceutical history, hiring thousands of reps to go across the country and market this drug.

Mapping Cholera

John Snow began to realized cases were clustered around the Broad Street water pump. He mapped incidents of Cholera in the neighborhood and talked to locals to come up with his theory that the disease was spread through the water. This event is considered the founding event in epidemiology.

Effects of Cholera

John Snow convinced the local council to dismantle the water pump but did not convince them the disease was not due to miasma. Regardless, the city of London did start massive construction in creating more and cleaner sewers. Dysentery and Typhoid were also major killers at this time linked to sanitation, along with national pride, in reasoning for cleaning up waterways.

Purdue Pharma & the Sacklers

Purdue Pharma is owned by the Sacklers who are philanthropists who have donated hundreds of millions of dollars to arts and medical research. FDA approved OxyContin for the market without any clinical trials regarding the addictive nature of the drug or how prone to abuse it was. The FDA examiner overseeing this case took a job at Purdue Pharma two years later. They marketed it saying it was not addictive without any scientific evidence. They heavily stressed and marketed the time-release capabilities, which were said to last 12 hours. Within a year, physicians were prescribing it in 8-hour intervals because it was not lasting the 12-hours promised. They funded a study that showed these same results that they never published. They knew there were cheaper alternatives at the 8-hour interval so they continued to push the 12-hour intervals in their product, knowing it wasn't true. Purdue Pharma spurred the Opioid epidemic in America. They had been sued thousands of times with with lots of notable losses such as the state of Oklahoma settling for $270 million. This is nothing compared to the 35 billion OxyContin had generated for Purdue Pharma since release.

Lessons

Struck first during Industrial Revolution, spread through filthy waterway, two ideas were miasma and water, John Snow convinced authorities to shut down Broad Street pump (founding of epidemiology), partially responsible for Public Health Act of 1848 and London's modernization of the sewer system even though proponents behind both believed in the miasma theory.

John Snow - physician

The miasma theory led to efforts to improve sanitation throughout the country. Snow published an essay, "On the Mode of Communication of Cholera", in 1849 that discarded the miasma theory. He stated Cholera affected the alimentary system first and foremost and this was his bases for his hypothesis because if it was due to the air it should affect the lungs first. He believed it was spread by contact with the affected, resulting in ingestion of something akin to intestinal worms.

Treating Opioid addition

This is must more tricky than treating an epidemic such as Cholera because addiction is much more complicated. The CDC released new guidelines to prescribing Opioids in 2018 for chronic pain which lowered the dosage recommendations. In 50% of states, patients cannot fill an opioid prescription for more than 3 to 7 days. There is also a nationwide push to expanding addiction research and treatment. NEGATIVES Pushing physicians to limit prescriptions have coincided with a massive uptick in use of synthetic opioids along with limiting the amount of days' worth of pills that patients can legally get from their pharmacies. Furthermore, treating addiction is heavily contested with facilities and physicians not wanting to use medication-assisted treatments.

Effects of the black death

First wave wiped out 60% of Europe. Lead to lower land prices because of all the death, land became available. Also, increased wages and stagnation of population growth until the end of the 15th century.

Causes

Caused by a bacterium called Cholera Vibrio. Isolated and shown to produce Cholera in 1884 by Robert Koch. Prior to the understanding of germ theory, the leading theory of disease causation was the miasma theory (caused by bad air). The build up of the filth, waste, and excrements around the cities and in the waterways caused the disease, according to the theory. Not everyone agreed with this theory at the time.

Cholera comes to town

Cholera had been present in India for centuries but began to spread west with the growth of steam travel. 50% of the people that contracted it died and it caused horrible symptoms. They suffered from dehydration, vomiting, and uncontrollable defecation. The fluid loss led to tissue collapse, a characteristic blue tinge to the skin, and ultimately organ failure due to struggles to compensate for fluid loss in kidneys and heart. Cholera remains a consistent plague within London and England, cropping up repeatedly over the next few decades.

London before Cholera

Cholera hit London in 1831, when they were in the midst of the Industrial Revolution. This led to sever overcrowding and city expansion. Waste removal, poor ventilation, heating, and water systems suffered because of this. People typically disposed of their waste in the local cesspit, the streets, or local waterways - which leaked into the water table. The Thames was clogged with trash, sewage, dead animals, and runoff of industrial pollutants.

The numbers

From 1999 to 2017 about 400,000 people were estimated to have died from an overdose involving opioids. Opioids accounted for 68% of drug overdoses in 2017. Dramatic increase in drug overdose from year to year. The most common drugs involved in these deaths were Methadone, OxyContin, and Vicodin.

Lessons

Opioids have long history of use in medicine, and known to be addictive for Millenia. Over 400,000 people have died from overdose since OxyContin. Purdue Pharma's aggressive, misleading marketing tactic led to chronic treatment with opioids - long-term and high dose. OxyContin acted as catalyst for opioid epidemic. The most prominent solutions to combat this are to limit prescriptions, and invest in addiction research and treatment.

From Prescriptions to Epidemic

Opioids quickly and easily create a physical dependence to that the body becomes physiologically adapted to their presence. OxyContin is a prescription and is expensive, so people will turn to heroin or fentanyl because they are a much cheaper alternative. 4 out of 5 heroin addicts started with prescription painkillers. Also, prolonged opioid use results in tolerance. As the body becomes more tolerant, a higher and higher dose is needed to reach the same euphoric state. It is also important to note the nasty withdrawal symptoms.

Preventing the Plague

Religious ceremonies were held enforcing new morality laws. Flagellating to atone for sins. Required disposal of bodies outside of town, avoid sick, burn clothes of dead, light fires in streets, and remove excrement from the city. The most common advice was to flee to putrid air. This is where we see the first form of quarantining.

Treating Cholera

Removing the bad air from the cities was slow to show improvement. People that contracted the virus were treated with confinement to bed, rest, and soothing teas. Physicians would prescribe calomel when the fever commenced. This would just add to the vomiting and defecation. Physicians did not have good results from this treatment.

Causes

The black death is caused by a bacterium called Yersinia pestis. This is spread through and affects many rodents. When bitten by an infected flea, the plague causes large painful swellings, that appear in the groin, armpit, and neck as the bacteria attacks the lymphatic system. They also suffer from high fevers, delirium or stupor, and organ failure. Kills people within 3 to 5 days 60% of the time. A more virulent form of it is called pneumonic plague, which is spread by contact with infected people. This form kills people in less than 3 days. CAUSES Celestial or supernatural causes. Terrestrial or natural causes. God's wrath. Miasma