What the Heroin Epidemic can Teach Us About Tolerance

I’ve been seeing stories all over the place about the heroin epidemic.  It is terribly sad.  I watched an episode of 60 minutes recently where they were talking about the epidemic and whether heroin addicts should be treated as criminals or medical patients.

That is a debate I’m going to save for another day, but there was a really, really important nugget of information regarding pharmacology/pharmacokinetics within that story that really jumped out at me.  They had a former nurse who had been around patients for years and she had stated that the most common time for them to die of overdose was after they had been abstinent for a period of time.

Let’s explore this a little bit and I will tell you why this makes sense.  Remember the term tolerance?  Tolerance is incredibly common with opioids.  Tolerance essentially means that over time, you will need higher and higher doses to get the same effect from the medication.  Tolerance is the reason you can have patients on ridiculously high morphine equivalents and they can walk around like normal without toxicity.

What happens when people abstain (or stop taking opioids), is that the tolerance that was previously developed from consistent use of opioids slowly disappears over time.  So what this nurse saw was that patients who abstained during treatment programs (2 weeks, 4 weeks etc.) and then relapsed, would take the same dose they had historically taken.  This “usual” or tolerable dose before may now be lethal as their tolerance is no longer what it once was.

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  1. gaber

    the same goes for methadone, if a patient missed his treatment , back to morphine or other street drug then he shows again in the rehab. clinic , he should be started on a different dose , not the same dose he used to take .

  2. deeone

    Downregulation of opioid receptors ocurrs during abstinence. Thus when they take the say dose as previously, there are less receptors for the opioids to bind to. Thus free opioid levels in the blood is higher than previously (i.e. prior to abstinence). The higher blood levels mean the respiratory center in the brain is stimulated by a large dose of opioid that previously, leading to respiratory depression and unfortunately death. I once worked in an addiction clinic where the was zero tolerance for giving supervised doses if the client had missed 3+ days supply, specifically because of this risk. P.S. remember that opioid receptors are proteins. It takes the body some time (days to weeks, depending on genetics) to synthesis these opioid receptors in the initial time period when the opioid is first started (i.e. the upregulation of opioid receptors, prior to tolerance). The lag time in synthesis of opioid receptors is the most common period during which people overdose, after a period of abstinence.

    • Felipe

      Nicely said


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Written By Eric Christianson

May 15, 2016

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