fentanyl UPPING THE ANTE

alcohol and marijuana have always played a significant role in drug use and have often been called gateway drugs. However, the true gateway drug is nicotine from tobacco. All of that said, the popularity of different drugs differed from one decade to another.

In the 1960s, the drug of the day was marijuana. In the 1970s, cocaine was king. In the 1980s, crack took over from cocaine. In the 1990s, methamphetamine stimulated everyone. In the 2000s, prescription opioids made their debut and continued to surge in the 2010s. In a manner of upping the ante, the 2020s saw the influx of fentanyl.

What is most notable and scary, however, is that during the past 20 years the drug of choice has been some form of opioid with increasing potency. From 2020 to the present time, those of us in Addiction Medicine have seen a decrease in urine drug screens being positive for heroin and an increase in urine drug screens being positive for fentanyl. Today, fentanyl is the predominate drug of choice. With approximately 100,000 overdose deaths in the United States each year, two-thirds of them are the result of an opioid and most of them are secondary to fentanyl.

The historic drug cartels have all but abandoned heroin in favor of fentanyl. In the past, heroin was smuggled into the country and dubbed “bricks” because it was packaged in sizes that resembled bricks. One “brick” of heroin can equate to the size of a small deck of cards of fentanyl, so the small size and increased potency make it more favorable to smuggle.

Because of its potency, even a small amount of fentanyl contamination can cause an overdose in a patient who believes they were using one drug and ended up using fentanyl. Drug dealers supply a multitude of drug options from marijuana to cocaine and methamphetamines. I often sarcastically complain that the drug dealers need a Vice President of Quality Assurance because we have seen all these substances contaminated with fentanyl.

Fentanyl has a stronger affinity to the mu opioid receptor than either methadone or buprenorphine, the two opioids used for treating opioid use disorder. This has caused a major change in the management of opioid use disorder.

When heroin and prescription opioids were popular, methadone could be titrated to a dose that took away a patient’s cravings. It could also be titrated to a dose that blocked the effects of heroin by attaching to all the available mu opioid receptor sites. But methadone, at any dose, may not block the effects of fentanyl.

In the past, a trough plasma level of methadone could be monitored to see if there was sufficient methadone to be considered a therapeutic or a blocking dose, knowing that the peak level would be even higher. But with the shift to fentanyl, it is now necessary to check a peak level of methadone to ensure that the patient is not nearing a toxic dose. Adding to this is the difficulty in obtaining a peak plasma level of methadone compared to the ease of obtaining a trough level.

A trough level can be drawn immediately before the patient receives their methadone, but a peak plasma level needs to be drawn 2 hours after the dose is given. Logistically, having a patient receive a dose of medication and then return later for a blood test can often be problematic. Furthermore, higher dosing of methadone also requires monitoring for possible QT-prolongation, a dangerous potential side effect of methadone.

The increased use of fentanyl has also caused a change in the use of buprenorphine for opioid use disorder. When heroin and other opioids were predominant, inducting to buprenorphine only required 8 to 18 hours of abstinence to avoid precipitated withdrawal.

With fentanyl, precipitated withdrawal has been known to occur up to 48 hours of abstinence before inducting with buprenorphine. Although the central effects of withdrawal from fentanyl begin in 8 to 12 hours, the peripheral effects of withdrawal may not start before 24 to 48 hours. This may be because with chronic abuse of fentanyl it is known to become stored in fatty tissue. The patient may feel withdrawal in the way of anxiety 8 to 12 hours after the last use, but the peripheral symptoms of withdrawal (nausea, vomiting, diarrhea, perspiration) may take 24 hours or longer to appear. If buprenorphine is given when only central symptoms are present, precipitated withdrawal can result.

When working with a schedule filled with so many patients, each needing our undivided attention for individual care, it is sometimes easy to miss the big picture. We need to remember that addiction is one disease, not multiple diseases. A person suffers from addiction, but the disease of addiction can be fed by multiple substances. Each substance feeding the disease of addiction may require a slightly, or massively, different approach.

As we adjust our efforts to care for patients using fentanyl, cocaine, or alcohol, we need to remind ourselves that we are not treating fentanyl addiction, cocaine addiction, or alcohol addiction. We are simply treating addiction that is being fed by different substances.