What are opioids? An opioid is a drug that is typically prescribed medication intended for pain relief. They work by binding to receptors in a person’s cells in the brain and throughout the body. There are natural opioids produced within the body like endorphins, a hormone secreted within the brain that cause and analgesic or relieving effect, which help to relieve a person’s pain sometimes this reliefs is not enough. This is where opioids like codeine and fentanyl come in. They help to reduce the perception of pain even more than a person can naturally, which is of great use to a person with a serious injury. Opioids do this by binding to certain pain receptors such as Mu, Kappa, and Delta and send signals to the brain to block pain. The problem with opioids is that they also affect the pleasure system which can lead to addiction and frequent use can lead to a tolerance of the drug and subsequently the opioid being less effective. What are the mechanics of the Opioid Crisis, why are they dangerous, understanding pain transmission and mechanisms and strategies to develop next-gen pain therapy.
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The opioid crisis is a problem in the United States that is only progressively getting worse. According to Ajay Yekkirala’s presentation, The Opioid Crisis: The Quest for Superior Analgesics, over 40% of all Americans visit the clinic every year due to chronic pain such as Arthritis thus causing a high demand for pain killers. The financial costs of pain to society range from 560 billion dollars to 635 billion dollars. This cost is much more than heart disease at 309 billion, cancer at 243 billion and diabetes at 183 billion. In 2017 there were 58 opioid prescriptions for every 100 Americans with 214 million written in total. 17% of Americans had at least one opioid prescription with an average of 3.4 dispensed per patient according to the United States’ Center for Disease Control. This has helped many people with pain so what is wrong with Opioids? In a word addiction. In 2016, around 48.5 million people report abuse of drugs, 4.3% percent or 2.1 million of these abused opioids and the numbers are only increasing. This crisis took flight in the 1990’s upon pharmaceutical companies ensuring that opioids were not addictive and prescribing them at greater rates. This led to widespread diversion and misuse before it was verified that they were in fact addictive (NIH). According to the National Institute on Drug Abuse or NIH, 21 to 29 percent of patients who are prescribed pain killers misuse them and 8 to 12 percent develop an opioid use disorder. The sheer size of the opioid crisis has made it a public health crisis with horrible consequence with around 130 deaths per day in the United States due to overdose becoming the number one cause of death in America. Why are they dangerous?
Opioid addiction causes physical dependence which leads to withdrawal symptoms upon ceasing taking them. Some of these are confusion, slowed breathing, blurred vision and stiff muscles. It becomes fatal; however, upon overdosing which stops breathing as opioid active neurons in the pre-botzinger complex in the brainstem that regulates a person’s breathing. Another effect of an opioid addiction is tolerance to the drug. Repeated use of opioids, as with almost every other prescription drug, reduces the therapeutic effect of the drug. This leads to the need to increase dosage to get the same pain relieving effect for the patient; however tolerance to this develops slowly which can then lead to the overdose situation.
We are taking steps to help prevent this. According to Ajay’s presentation, the United States’ government is taking steps to prevent opioid addiction. All opioids are now schedule 2 drugs in the United States which makes them difficult to prescribe. Schedule 2 means that they are controlled substances that have a high chance for abuse by those prescribed it. The abuse can lead to severe psychological or physical dependence. Caps that are being placed on the pain killer’s production are also limiting production as and availability as time progresses. In the case of an opioid overdose, Narcan, a nasal spray used for opioid overdose treatment and the slowing of breathing, has been made available to first responders around the United States. Reductions in opioid availability causes its own problem as there are many unmet needs for pain medication.
Another solution to the opioid crisis is the creation of new drugs that do not have the side effects of narcotics, but to do this we have t understand how opioids affect the body and deal with pain. Pain can be classified in three ways: noxious pain that acts as a warning system, inflammatory pain which is sensitivity due to pain, and pathological which is damage to the nervous system or abnormal functions. Opioids work by targeting Mu receptor, which leads to pain relief and, unfortunately, often addiction. Opioids help to block Ion Channels, passageways made of excitable cells that send electrical signals through the body. Different compounds can help to open and close these channels. Blocking ion channels is the goal of next gen pain therapy. There has been some success with Sodium channel ligands such as local anesthetics like lidocaine and VX-150 which is in Phase 2 clinical trials. Other option like Potassium channel opener are under pre-clinical development. Calcium channel ligands like Gabapentin have seen a little success in dealing with nervous pain. Another development is the introduction of abuse deterrent opioids. While thus far we there is not the ability change the active drug , opioids, it is possible to create pill formation that cannot be crushed or melted, but the need for a safer pain killer is still great.
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This is where Blue Therapeutics work begins to shine. Blue Therapeutics is an early- stage biotechnology company focused on creating potent non-addictive pain killers. Their Blue 181 targets the spinal cord to prevent the negative side effects that come from opioids entering the brain while maintaining the positives from the analgesic or relieving effect.
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