Between death and painless life... ‘Decision to break up’ Seorae’s choice

23-05-15

[Hankyoreh S] Shin Chan-young's poison to the mind, medicine to the mind - Fentanyl

It makes me forget the pain of dying

100 times stronger action than morphine

‘Death of misuse’ becomes a social problem

Spurring the development of drugs that eliminate addiction

“I sent it the way I wanted it. Four fentanyl capsules are enough. I also took four.”

This passage appears in “Decision to Break Up,” which former US President Barack Obama picked as one of the best films of 2022 on social media. The heroine Seorae (Tang Wei) uses fentanyl to carry out her 'determination' when her mother, suffering from her illness, demands that she die with dignity. And she sticks another 4 fentanyl capsules under her mother's urn for the last moments of her own life, which until then was hopeless for her.

Everyone wants to live a life without pain, the pain of being hurt or sick in the body. Even if we regard heartache as an unavoidable tax that we have to go through because we are human beings with high-level brain functions, it is difficult to understand what kind of evolutionary advantage that terrible physical pain has to survival. The extreme pain caused by childbirth, terminal cancer, major accidents, burns, and nerve or brain damage is tearful even for those around you, not to mention yourself.

Unfortunately or fortunately, mankind has already used the poppy and the opium obtained from it as a powerful pain reliever since the Neolithic Age. Of course, it was with a serious problem called 'opium addiction'. Just as aspirin was synthesized from the analgesic action of willow bark, a substance that mediates the pharmacological action of opium was discovered in Germany in 1805. It came to be called 'morphine' after Morpheus. The commercial success of morphine became the basis for ‘Merck’, the world’s longest-serving global pharmaceutical company.

Pain relief, but too strong action

The price for making me forget the pain was high. Narcotic pain relievers (opioids) are the leading cause of death among young adults in the United States. The problem of abuse of opioids is dealt with in several documentaries, including the films <Requiem>, <The Last Narc>, and <Death Painkiller>, and in our movie <Resolve to Break Up>, the setting that the main character has fentanyl is shown. The abuse and misuse of oxycodone, which was used as a narcotic analgesic, is so severe that the term ‘oxycodone epidemic’ is being used, and recently, a drug called fentanyl seems to have taken over.

Fentanyl is a widely used opioid analgesic with a potent effect 100 times that of morphine and 50 times that of heroin. This year, the U.S. Drug Enforcement Administration shocked the public by revealing that it had seized enough fentanyl to kill the entire United States. The root of the problem is the overdose or misuse of opioids by those who do not need them, and the abuse of opioids by those who do not need them. In the United States, doctors who prescribe excessive narcotic painkillers and cause addiction problems are sometimes referred to as “pill mills.”

Opioid-based substances basically have strong analgesic action and stop coughing, and stop diarrhea by suppressing excessive intestinal movement. Therefore, it can be used as an analgesic, antitussive, and antidiarrheal. In addition, it produces effects such as reducing anxiety, inducing feelings of happiness and euphoria in the central nervous system, and mediates addiction and dependence.

Scenes in movies and novels depicting people who smoked opium becoming numb and stretched out around them as if they were sleeping show this effect. In addition, opioid substances inhibit breathing, stimulate the vomiting center of the medulla oblongata, cause nausea and vomiting, and release histamine to cause itching, such as when bitten by mosquitoes and allergic. The biggest problem is that it suppresses breathing, so if you ingest an excessive amount, it can lead to death through respiratory paralysis.

Opioids have tolerance and dependence. In other words, in order to obtain the same level of analgesic effect and euphoria, more and more narcotic analgesics must be administered. On the other hand, effects such as inhibition of intestinal movement, induction of convulsions, constriction of the pupil, and suppression of the heart have relatively low tolerance, resulting in symptoms such as extreme constipation and skin and tissue damage due to itching as the dose of the analgesic increases. Substances in this class have very strong dependence, so even short-term administration often leads to addiction, and the dose is gradually increased according to tolerance.

If you stop taking the drug after you become addicted to it, you will experience very severe withdrawal symptoms. Withdrawal symptoms can be thought of as reversing the action of opioids. They feel pain even when they are still, and show anxiety, insomnia, aggression, and fear and hostility. Breathing quickens, blood pressure rises, pupils dilate, and severe diarrhea is experienced. Opioid-based substances such as heroin are considered to be the most harmful substances to society, including mental and physical dependence and damage among all dependence-inducing substances.

Administrative, judicial, and social regulations and help, such as narcotic and drug prescription management and addiction control, are desperately needed to solve the problem of narcotic analgesics, but fundamentally, a scientific approach is important. Researchers at the University of Houston have proposed a way to control addiction by suppressing the euphoria of fentanyl by preventing antibodies and fentanyl from binding and entering the brain through a fentanyl vaccine. In addition to relieving addiction and withdrawal symptoms by traditional drug therapies, addiction treatment using digital therapeutics has been approved by the US Food and Drug Administration (FDA) and is commercially available.

Will the best non-narcotic analgesic be realized?

Studies on pain control by electromagnetic stimulation of brain regions, which are important for central and psychogenic pain control, are also being actively conducted. In 2017, researchers at the Scripps Research Institute in the U.S. found that when fentanyl binds to a protein called mu receptor, respiratory paralysis side effects are large, but when the same receptor activates only the G protein signal, the pain relief effect is large but the respiratory paralysis side effects are small. >(Cell) reported.

Based on this, an opioid analgesic with more selective analgesia and fewer respiratory paralysis side effects was approved by the US Food and Drug Administration in 2020. Through similar selective signaling research, research is also underway to develop a drug with less induction of euphoria and excellent analgesia. Research is also underway to develop a non-narcotic, strong and long-lasting pain reliever using several ion channel proteins and receptors in addition to opioid receptors. Pain control, at least in the scientific community, is making a 'determination to break up' with opiate addiction. I look forward to the day when the fight against pain is finally won and fentanyl will disappear into the back of history.