By: Dr. Francisco Rojas
Naloxone is an antagonist that competes for the same receptors as opioid agonists such as heroin and fentanyl. Naloxone pushes those drugs out and takes their place, but it doesn’t turn on the opioid receptors when it binds to them, so it produces no opioid high. Because naloxone prevents those other opioids from acting, it is used in opioid overdoses to counteract life-threatening depression of the central nervous system and respiratory system, allowing an overdose victim to breathe normally. Although naloxone is a prescription drug, it is not a controlled substance and has no abuse potential.
In the past 15 years, the death rate from prescription opioid-associated overdose nearly quadrupled from 1999 to 2013, while deaths from heroin alone more than tripled from 2010 to 2014.Together, heroin and prescription pain medications take the lives of more than 28,000 Americans per year —over 75 people per day. They also cause hundreds of thousands of non-fatal overdoses and an incalculable amount of emotional suffering and preventable health care expenses.
The synthesis of naloxone was the result of chemical modifications of other opioids. Chemists knew that adding a hydroxyl group to the carbon next to an opioid’s amine would increase the drug’s potency. This is the case for oxymorphone, which has this alcohol group and is 10 times more potent as a painkiller than morphine. However, replacing the methylamine group of oxymorphone with an allylamine, the result is the antagonist naloxone. The new compound was found to reverse the effects of every opioid they tested it against. Jack Fishman and Mozes Lewenstein filed for the U.S. patent on naloxone in 1961.
FDA approved naloxone for treating opioid overdoses in 1971. Before 2014, the only approved way of delivering naloxone was via injection, either into a vein or a muscle. But giving an injection can be difficult for someone without medical training. Fortunately, two new products have recently been approved by the FDA: An autoinjector called Evzio in 2014, and last November a nasal spray under the name of Narcan. They are easy to use and effective at reversing overdoses. In a human use trial that was required for approval, 90% of first-time users were able to use the spray correctly. This data will encourage more widespread naloxone use in the U.S., and hopefully, help keep prices for the devices down. The ability to reverse an opioid overdose is highly dependent on time elapsed since ingestion. So it‘s expected that expanding access to these devices to people who might be present during an overdose, will extend the small time window in which an overdose can be reversed before brain damage or death occurs.
Access to naloxone has historically been limited by laws and regulations that pre-date the overdose epidemic. In an attempt to reverse the unprecedented increase in preventable overdose deaths, the majority of states have recently amended those laws to increase access to emergency care and treatment for opiate overdose. These changes come in two general views. The first encourages the wider prescription and use of naloxone by clarifying that prescribers acting in good faith may prescribe the drug to persons who may be able to use it to reverse overdose and by removing the possibility of negative legal action against prescribers and lay administrators. The second encourages bystanders to become “Good Samaritans” by summoning emergency responders without fear of arrest or other negative legal consequences. The effort is to get naloxone into the hands of friends, family members, and other bystanders.
Not everyone agrees naloxone is beneficial. Critics say that naloxone does not truly save lives; it merely extends them until the next overdose. They imply that naloxone will only foster addiction and that it gives drug users a safety net, allowing some to overdose numerous times in safety. Interestingly, similar criticisms were argued about needle exchange programs to fight HIV. Critics delayed the implementation of the program because it was encouraging more risk taking. But when New York state expanded access to clean needles, HIV infection rates in drug users fell from 54% in 1990 to only 3% by 2012.
So let’s not make the same mistake with the opioid epidemic by promoting baseless and ill informed fears about naloxone. We need to push for making the drug available to anyone who might witness an overdose and can respond more quickly than paramedics. Policy decisions on the opioid crisis must be made based on science, not stigma. Addiction is a disease. We must treat it with the same urgency, humanity and compassion as we treat all diseases.
Rudd, R.A., Aleshire, N., Zibbell, J.E., Gladden, M., 2015. Increases in Drug and Opioid Overdose Deaths —United States, 2000–2014. Morbidity and Mortality Weekly Report (MMWR) 64, 1-5
Chemical & Engineering News, May 16, 2016, p34.