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Your Captain Speaking: Key, Locks, and Doors—an Explanation of Opioids

Kevin is a good resource to ask how opioids work and naloxone stops them. We worked together for many years on the streets; then, with that solid base of experience, he went on to get his doctorate in pharmacy.

He uses an analogy of keys opening and closing doors. The idea of cells responding to certain “keys” is not new,1 and it’s not a perfect analogy in all respects, but it does help me remember how things work and picture what’s happening with my patient.

Each cell has receptors—essentially doors in the cell membrane to let things in. Think of opioid molecules as little keys that unlock and open these doors. If one finds a receptor, it pushes the door open and holds it. While the door is open, it produces an effect. Some effects are desired, some aren’t, and others we just notice.

If the receptors in the respiratory center of the brain are involved, the medulla oblongata and pons portion of the brain stem, respiratory rate and depth are suppressed. Just about all the core signals of the body go through the medulla. Taking it offline is like cutting the strings on a puppet: Everything stops. The drive to breathe is generated by CO2 levels and backed up by O2 levels. It can get switched off if the opioid level is high enough; then bad things happen.

Morphine will unlock the door and push it open rather gently. Paramedics know when we give morphine it takes several minutes to take effect. It will hold the door open for 2–4 hours. The door also closes more gently with morphine than other opioids.

Drugs like fentanyl and, even worse, carfentanil not only unlock the door but kick it open hard and try to jam it open. The cell has a much harder time diluting and degrading this attachment to the cell receptor.

Naloxone to the rescue, but with limits. Naloxone has a key too, but if there’s already a key in the door, you can’t simply put another key into the receptor lock! Naloxone can’t do anything at that specific cell, so it moves along looking for another. It will push its way to the head of the line, though, in front of any other opiates and into available receptors—and then closes and locks those doors. And it keeps them shut; having that key in the door prevents other opioids from opening it.

However, like other opioids, the naloxone keys are biodegradable and wear down over time. As the naloxone degrades and those locks become available again, opioids remaining in the bloodstream and still unlock and open those doors. When that happens their effects appear again.

When an opioid key has unlocked and opened a cell door, the cell itself must biodegrade the opioid key and its effects. Opioids floating in the bloodstream that have yet to connect with a cell are ultimately metabolized, removed from the bloodstream over time by the liver, and then excreted.


1. The Conversation. Explainer: how do drugs work? 2016 Apr 28;

Dick Blanchet (ret.), BS, MBA, worked as a paramedic for Abbott EMS in St. Louis and Illinois for more than 22 years. He was also a captain with Atlas Air for 22 years.

Kevin Blanchet, BS, PharmD, worked as an EMT for 16 years with Abbott EMS in St. Louis and Illinois before attending the Auburn University Harrison School of Pharmacy. He graduated with his doctorate in 2005. He has worked since at both retail and hospital-based pharmacies.


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