Heroin-why so many recent overdose-related deaths?

     Heroin addition is reaching epidemic proportions here in Kentucky and in much of the United States.  Many of the recent over-dose related deaths have been traced to the presence of other substances, fentanyl and carfentanil in a particular batch of heroin ((174 related overdose deaths)(Time article).  Why would the addition of these two substances increase the toxic effects of heroin?  To address this question, we need to first examine some of the pharmacological properties heroin carfentanil, and fentanyl.  All of these are metabolized to morphine, their pharmacologically active form.  The morphine molecule binds directly to the opioid mu receptor and it is this interaction that initiates all of the drug effects.  Carfentenil is not approved for use in the human population and is used for veterinarian purposes.

     The potencies of these drugs are often expressed as relative values with morphine provided with a value of 1.  The potencies are as follows when the drugs are administered similarly:

• Morphine = 1X 
• Heroin= ~2X
• Fentanyl = ~100X 
• Carfentanil = ~10,000X.  

     Since the active ingredient, morphine, is the same for all of these, this means that the increases in potency of drugs like fentanyl and carfenanil relative to morphine and heroin are because more morphine is able to interact with more opioid mu receptors in the brain.


     If we take a look at the pharmacokinetics of these different drugs, we can then understand  why these different potencies exist.  A brief review of these drugs is found here.  The high potency of fentanyl and carfentanil is thought to be due to their high lipophilicity.  For example, the lipid solubility of fentanyl is reported to be approximately 9500 whereas that of morphine is approximately 6.   Other differences in pharmacokinetics that impact on the actions of these two drugs are:

                                                               Heroin                                   Fentanyl

Half-life                                               > 10 min                                   3-12 hours
Bioavailability                                     ~35%                                        92%
Clearance                                          930 L/hr                                       27-75 L/hr

What these numbers mean is that as compared to heroin, fentanyl is cleared from the body much more rapidly, thus more active drug is available for (once metabolized to morphine) to bind the opioid mu receptors.