Episode 59- “Something old, something new:” Propylhexedrine abuse

Hello and welcome to Episode 59 of ER-Rx. It seems like almost every day we hear about new drugs of abuse or new ways to abuse old drugs. As someone who works in healthcare, it’s really hard to keep up with. That’s why this week, we’re going to talk about the abuse potential of an old, unscheduled, over-the-counter (OTC) medication that’s been all the rage recently online- prompting the FDA to issue a warning in March of 2021.

This warning stated that the use and abuse of the OTC nasal decongestant propylhexedrine (brand name Benzedrex) can lead to serious harm including heart and mental health problems. These problems can lead to hospitalization, disability, and death. In their review of US poison control center calls they found 460 cases of abuse and misuse, with 21 of these being life-threatening and 13 requiring ICU admission.

So, what is propylhexedrine, how does it work, and why is it abused? Propylhexedrine is used to relieve nasal congestion from colds, allergic rhinitis, and sinusitis. The label says to use two inhalations per nostril every two hours, delivering 0.4 to 0.5 mg of propylhexedrine. It was developed as a substitute for amphetamines in the 1940s due to the growing number of people who would extract amphetamines from inhalers. At this time, it is not a scheduled substance in the US, even though it is structurally related to amphetamines. This is why it’s been used as a quote-on-quote “legal high” dating back to the 1970s and 1980s.

Upon oral ingestion, propylhexedrine is rapidly absorbed from the GI tract. In humans, it results in greater peripheral adrenergic stimulation compared to its CNS effects- having only 1/12ths the CNS stimulant effects of amphetamines. In short, it works by leading to more norepinephrine, dopamine, and serotonin release, much like the amphetamines. Unlike the amphetamines, it promotes more peripheral adrenergic stimulation as opposed to dopaminergic and serotonergic release. This means that abuse of propylhexedrine mimics the effects of amphetamines to a degree, but with more profound end-organ complications given its higher hypertensive and vasoconstrictive effects.

The most common source of propylhexedrine is nasal decongestant inhalers. Each inhaler contains 250 mg of propylhexedrine. Reported doses for abuse range from 125 mg to 1250 mg. Patients purchase nasal decongestants, take out the cotton filaments which are soaked in the drug, and swallow them. Some patients even “parachute” them, where they wrap the filaments in tissue paper to create a sort of sustained release product where the tissue paper gradually dissolves and exposes more of the filament for absorption over time.

To combat the growing abuse of the drug, in the warning issued by the FDA, they requested that all manufacturers of OTC propylhexedrine consider changing their product designs to make it harder to extract the drug and also to reduce the amount of drug in the device.

Described online as a “stimulant of last resort,” it can cause euphoria, anxiety, and wakefulness. But don’t get too excited— like all drugs of abuse the risks far outweigh the so-called “benefits.” It can lead to increased heart rate and blood pressure, hyperthermia, arrhythmias, hallucinations, delusions, seizures, and even death. If parachuted, it can cause intestinal impaction and aspiration. Long term use can lead to lung damage if inhaled and structural cardiac changes. To make matters worse, the “comedown” from this agent can lead to fatigue, irritability, depression, and insomnia, to name just a few.

Similar to methamphetamine abuse, management in the ER is mainly symptomatic and supportive. Think agitation, tachycardia, hypertension, hyperthermia, and seizures.

We’ll see how far the FDA will go to combat the growing abuse of the drug, or if manufacturers will really make it harder to extract the drug from its inhalers. But in the meantime, be on the look-out for patients presenting with amphetamine-like toxidromes, and consider that they may be abusing OTC nasal decongestant inhalers.

As always, thank you so much for your time. If you have any questions, comments, or anything to add to my discussion for this episode please leave a comment on errxpodcast.com or the @errxpodcast Instagram page. It’s been really fun having discussions with you guys online. Also remember that this show is available on Apple Podcasts, Google Podcasts, Pandora, Spotify, iHeartRadio, and even YouTube.