The opioid overdose crises is just another problem we created for ourselves when we decided our body’s little voice- the pain response is an unnecessary sensation that should be ignored. 16 years down the line we’ve kind of shut off these rational neurons that were easy to negotiate with using mild analgesics and ended up awakening a far worse nightmare – the opioid receptors.
Amidst the strive for health, fun and crazy dieting habits on the verge, opioid overdose crisis claims the lives of more than 115 Americans per day. Overdose deaths now surpass car accidents as the leading cause of accidental deaths. More than 66% of drug overdose deaths are attributed to opioids use in the U.S. According to The Centers for Disease Control and Prevention (CDC) 2016 statistics, the number of opioid overdose deaths including heroin and prescription opioids like oxycodone fentanyl, methadone and hydrocodone exhibited a 5 times rise compared to 1999 cases. Between 2000 to 2015 over 600, 000 people died from drug overdoses.
Narcan, another name for naloxone, is a non-selective competitive receptor antagonist that acts by reversing major life-threatening effects of opioid overdose like the Central nervous system and respiratory system depression within only a few minutes. Even though effects don’t last long, it gives one time to seek medical assistance. Most hospitals provide naloxone prescription to patients on opiate drugs for the treatment of chronic pain or following detox.
Narcan is approved by the Food and Drug Association (FDA) and is among the WHO list of essential medicines. Narcan is considered one of the most effective and safe drugs for opioid overdose reversal. The drug is fairly affordable going at $0.50 to $5.39 per dose at wholesale price; a vial is sold at $25 in the United States while auto-injectors go for approximately $4,500, not a high price to pay to buy over 30 minutes to seek emergency medical care.
An understanding of what opiates do to the body can help us better understand how Narcan works. Opiates are naturally formed by the body during exercising or strenuous activities in the form of endorphins. Endorphins or endogenous opiates bind to opiate receptors in the brain cells leading to an alteration in how neurons communicate resulting in pain relief, stress reduction, happiness and feelings of pleasure; sounds familiar?
Endorphins also control the rate of breathing through action on the respiratory center.
Since the body is always working to maintain homeostasis, endorphins production is only in regulated amounts to meet desired functions. Exogenous opiates like prescription or recreational opiates work in the same mechanisms as endorphins produced by the body. However, in overdose, the opioids flood the central nervous system activating many opioid receptors at once, this leads to amplified effects “Rush.”
Narcan is a pure antagonist with no partial agonistic effect or morphine-like properties like most opioid antagonists. Because of this property, Narcan only works if one has opioids in their system and elicits no pharmacological effects in people who have no opioids in their system. Chemically, Narcan is a congener of oxymorphone differing slightly in structure with a methyl group to alkyl group substitution on the nitrogen atom.
Though the mode of action of this drug is not fully understood, in vitro studies suggests that Narcan antagonizes Opioid actions by competing for the same binding sites on mu, kappa and delta opioid receptors in the brain. Narcan has the greatest affinity to mu receptor. The drug binds to this receptors displacing opioids from the binding sites and also occupies the binding sites locking them hence opioids binding is blocked. While it has an almost similar chemical structure as opiates, Nacarn bind the receptors but instead of activating the receptors to produce morphine-like effects it just sits at the binding site doing nothing.
Narcan is, therefore, an inhibitor of opioids since without binding the receptors opioids will not cause their usual effects. The overdose symptoms will immediately go away since the opioids are no longer sitting at the receptors. Free opioids that are not bound to receptors circulate in the blood and are eventually broken down in the liver and flushed out of the body through urine by the kidney.
While Narcan can reverse the symptoms of opioid overdose, this is a temporary relief. Narcan can be given as an injection or a nasal spray. The onset of action is approximately 5 minutes but Narcan has a half-life of only 30-80 minutes after which it is cleared from the body and opioids take over the receptors control again. Some people can relapse back to their initial state within minutes to hours hence seeking emergency medical care is essential in order to avoid adverse outcomes.
So next time you get an opioid prescription or even a malicious idea of “prescribing” it for yourself get naloxone/ Narcan. If you’re halfway through choosing your poison, you might as well get the antidote. Who knows it might just buy you 3 minutes to start the car or make a phone call for help.
Centers for Disease Control and Prevention (CDC. (2011). Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR. Morbidity and mortality weekly report, 60(43), 1487.
Curtin, S. C., Tejada-Vera, B., & Warner, M. (2017). Drug Overdose Deaths among Adolescents Aged 15-19 in the United States: 1999-2015. NCHS Data Brief. Number 282. National Center for Health Statistics.
Drolet, G., Dumont, É. C., Gosselin, I., Kinkead, R., Laforest, S., & Trottier, J. F. (2001). Role of endogenous opioid system in the regulation of the stress response. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25(4), 729-741.