In this video Dr. Darryl Inaba tells us how naloxone prevents death caused by opiate overdose.
The following column was published in the Fall 2016 issue of Advances in Addiction & Recovery; The Official Publication of NAADAC, the Association for Addiction Professionals. It explains how OTC Naloxone can help prevent death by accidental opiate over dose.
Opioid Antagonist: Issue of “Over-The-Counter” Naloxone
An Interview of Dr. Darryl S. Inaba, PharmD, CADC-V, CADC III
NAADAC: What is the best way for me to explain to my clients opioid agonists, antagonists, and partial agonist?
Dr. INABA: Opioids like oxycodone and heroin produce effects in the brain by attaching to specific sites on neurons known as receptors. These receptors are there to activate, modify or stop many actions that the brain processes every second through a process known as a synapse. This is how brain cells communicate to each other and to the rest of the body. Opioids bind to receptors that are present in the brain for its natural brain chemicals also known as endorphins. Think of the brain having some 5 or 6 different receptors for different endorphin molecules that result in decreasing pain, altering mood, mitigating stress, suppressing cough, and other effects that result from their activation. You can think of this like different padlocks on brain cells that are opened, partially opened, closed or plugged up when an opioid slips into a specific lock and is mistaken for one of the brain’s natural endorphin molecules. An opioid Agonist is a drug that binds to a receptor site and acts like or mimics the effect usually activated by the brain’s natural endorphin molecule. An Antagonist binds to the endorphin receptor site, does not activate it and sits in the receptor to block it from the action of opioids or endorphins. The antagonist is like a condom that covers the receptor site to prevent it from being activated. Partial Agonist/Antagonist only activates a portion of the receptor site resulting in partial effects and sits in the receptor to block other opioids or endorphins from activating that site. Opioids can also fit into some of the 5 different receptors and not others resulting in partial effects. Then, small doses of an opioid can fit into an endorphin receptor as an agonist but larger doses causes the receptor to hyperpolarize or “freeze up” like a lock that has been jammed. It then become an antagonist. This type of receptor site activity is known as an Inverse Agonist. (Inaba and Cohen, 2014; Brunton, L.L., et al., 2011; Lowenson, J.H., 2011)
NAADAC: How do naltrexone, naloxone and Buprenorphine differ?
Dr. INABA: Both naltrexone and naloxone are opioid antagonists and are often referred to as “pure antagonist” as they only block the opioid receptors without having any partial agonist activity. The chemical properties of naloxone make it poorly absorbed if taken orally or sublingually but is effective absorbed when snorted into the nasal passages and lungs. Naloxone is also very short-acting in the brain and is therefore used as an antidote for opioid overdose but only has a short duration of action (45 minute to 1 hour). Naltrexone can be absorbed by oral and sublingual routes of administration, is much longer acting (24 hours or longer), has some toxicity to the liver and may block some opioid receptors that naloxone doesn’t. Naltrexone is used as a prophylactic to block opioid addiction relapse by preventing their action if one slips during recovery. It has also been shown to decrease craving and is approved for both alcohol and opiate addiction treatment. Naltrexone has also been used to decrease cravings in pathological gambling, stimulant, and nicotine use disorders. Even behavioral disorders lik
e trichotillomania and kleptomania has responded to naltrexone therapy. (Aboujaoude E., Salame W.O., 2016; Lahti T, et al., 2010)
Buprenorphine is an opioid inverse agonist. This means that it has both opioid-like actions and can also be a blocker of opioids whereas naloxone and naltrexone only block opioid effects. At low doses it is a powerful opiate agonist even more powerful than morphine or heroin but as its dosage is increased it deactivated and blocks the opioid receptors in the brain to become an opioid antagonist. This action makes it safer to use both for the treatments of pain and opioid use disorder. By 2012, the Wall Street Journal gave a report on IMS (Inventory Management System) Health National Disease and Therapeutic Index that U.S. prescriptions for buprenorphine in the treatment of pain greatly outnumber methadone prescriptions. (WSJ, 2012)
NAADAC: Why the move to have opioid antagonists as “over the counter” medication?
Dr. INABA: Our nation is in the midst of a major opioid addiction and overdose death epidemic. The very grim evidence of such is incontrovertible:
- S. has 4.6% of the world’s population and consumes 80% of the worlds opioids, yet there is no or little evidence for their efficacy in the long-term treatment of chronic pain
- Prescriptions for opioids have more than tripled in the past 20 years
- By 2010 prescription overdose deaths, primarily opioids were greater than auto accident deaths in the U.S.
- The 2016 United Nations reports the U.S. having the highest drug overdose death rate in the world with a growing incidence of illicit fentanyl analogs laced heroin overdoses (Reuben, D.B., et al., 2015; UNODC 2016)
The tragedy of this is that an effective, easy to administer antidote with a minimum of side effects or concerns exists to counteract the lethal effects of opioid overdose. This antidote is naloxone especially in its newer nasal administration preparations. When sprayed into the nostrils, it will bring an opioid overdosed victim back into consciousness in a matter of seconds. When an accidental overdose occurs, it often takes several minutes to get the victim to an emergency room or for medical professionals to arrive with naloxone to treat the overdose. Many cities now provide their police officers and first responders with naloxone kits since they are more often there before medical help can arrive and many deaths have been averted. In my small city of Medford, Oregon police officers were provided with these kits last year and have been credited with saving several dozen lives in the first few months of being implemented. The Detox unit of the Addictions Recovery
Center where I work have begun to train and provide clients coming through our unit with these kits just two weeks ago and has already been credited for saving two lives. Needless opioid deaths continue to increase throughout the nation and the move is to now make naloxone kits available to everyone “over the counter” (non-prescription) so then anyone can purchase it and have it on hand when they come upon an opioid overdose. California (AB 1535 signed into law 2014) and other states have legislated availability of “over the counter” naloxone to combat the rash of opioid overdose death. I believe that this just makes common sense though there are some caveats to keep in mind. First and foremost, one should always make the 911 call to get emergency medical help intervention when using naloxone. Its duration of action is much shorter than that of most opioids so the overdosed victim may only temporarily come out of their coma only to go back into one when the naloxone wears off since the longer acting opioid will still be in their system. The victim may also have other medical problems or complication that can be addressed by getting formal medical assistance. Some of the illicit fentanyl analogs that are used to lace heroin are so powerful that naloxone may not effectively reverse their toxic effects. This also occurs when the user combines their opiates with other drugs especially with benzodiazepines and heavy drinking. Then there is the potential of precipitating opioid withdrawal symptoms when naloxone is used in a person who has developed physical addiction to opioids. Even when used in someone not physically addicted, the reversal of opioid effects can result in an angry and somewhat belligerent victim when they come back to consciousness that should be expected and prepared for. (Inaba and Cohen, 2014; Brunton, L.L., et al., 2011; Lowenson, J.H., 2011)
Those who struggle with substance related and addictive disorders do not fully engage in recovery until they come to desire it more than just about anything else. I have deep gratitude that naloxone has made it possible for thousands to come to that understanding. Sobriety is a change that can be accomplished before a person with addictive disorder experiences the ultimate consequence (death) from this powerful medical disorder. In many instances, naloxone has even hastened this understanding by bringing those with opioid use disorder back from the very edge of that consequence to provide them with a new sense of meaning and value for their future potential contributions to their families and communities.
Brunton, L.L., Chabner, Bruce, Knollmann, Björn C., eds. (2011). Goodman & Gillman’s The Pharmacological Basis of Therapeutics, 12th Edition, New York: McGraw-Hill.
Inaba, D.S., and Cohen, W.E. (2014). Uppers, Downers, All Arounder: Physical and Mental Effects of Psychoactive Drugs (8th Edition), Medford, OR:CNS Productions, Inc.
Lahti T., Halme J.T., Pankakoski M., Sinclair D., Alho H., (2010). Treatment of pathological gambling with naltrexone pharmacotherapy and brief intervention: a pilot study. Psychopharmacol Bull. 43(3):35-44.
Lowinson, J.H., Ruiz, P., Millman, R.B., Langrod, J.G. (2011). Substance Abuse – A comprehensive Textbook, 5th Edition, Philadelphia, Pa: Lippincott Williams & Wilkins.
Reuben, D.B., Alvanzo, A.A.H., Takamura, A., Bogat, G.A., Callahan, C.M., Ruffing, V., and Steffens, D.C., (2015), National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain. Ann Intern Med. 1/13/15 published on line: https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/opioids-chronic-pain/workship-resources#frinal report. Accessed 1/15/15.
UNODC (2016). World Drug Report 2016, http://www.unodc.org/wdr2016/ accessed 8/15/16.
Wall Street Journal, (2012). Painkiller Relief, page B3.