Adverse Effects & Risks
Adverse effects from ultra-potent opioids can manifest earlier and more severe when compared to regular opioids due to their increased potency. Some adverse effects of ultra-potent opioids include nausea, vomiting, itching, constipation, confusion, sedation, urinary retention and slowed breathing – which can lead to respiratory depression, coma and death.
The use of ultra-potent opioids come with the high risk of addiction, tolerance and physical dependence. Dependence can occur after just one experience with ultra-potent opioids. If you suspect someone you know is abusing opioids or ultra-potent opioids, look out for some of the signs mentioned below and reach out to them for help.
Symptoms of withdrawal include sweating, insomnia, a strong craving for opioids, muscle aches, agitation, vomiting, seizures, pulmonary edema and dysrhythmias. Some additional addiction, withdrawal and overdose symptoms can be found below.
Due to the extremely narrow therapeutic index of opioids, and especially ultra-potent opioids, overdose is more likely to occur. To avoid death, naloxone should be carried and used should the need arise. Increasingly higher doses of naloxone are needed to reverse the effects of ultra-potent opioid overdoses. This should be kept in mind when administering naloxone to users of ultra-potent opioids.
Drug-Drug Interactions
Most opioids are metabolized by one or more CYP450 enzymes, the primary ones being CYP3A4 & CYP2D6. CYP450 enzymes are predominantly liver enzymes that metabolize drugs in the body. Any drugs that induce or inhibit these specific CYP450 enzymes can impact how ultra-potent opioids behave in the body. For example, CYP3A4 can metabolize fentanyl into its inactive metabolite, norfentanyl, and therefore encourage its elimination from the body. However, if CYP3A4 is inhibited by another drug or compound, then fentanyl metabolism is greatly reduced and the risk of an overdose is significantly increased as fentanyl now has time to travel around the body in its active form and cause problems.
The herbal supplement St. John’s Wort induces CYP3A4, while grapefruit juice inhibits it. Cocaine is a strong inhibitor of CYP3A4 & CYP2D6 and MDMA inhibits just CYP2D6. For a more extensive look at inducers and inhibitors of CYP3A4 & CYP2D6, see below.
Fentanyl and fentanyl analogs interact with other Central Nervous System (CNS) sedative drugs like antihistamines, benzodiazepines, barbiturates, tranquilizers, anesthetics, antipsychotics, and other opioids leading to an increased effect on CNS depression.
Ultra-potent opioids used with heroin and/or alcohol increases CNS depression which can lead to serious side effects including respiratory distress, coma, and eventually death. Fentanyl and alcohol apply a synergistic depression on the cardio-circulatory system and can also increase nervous system side effects like drowsiness, dizziness and difficulty concentrating. Cocaine used with opioids excites the cardio-circulatory system and brings on hyperkinetic cardiac arrhythmia. Amphetamines when combined with ultra-potent opioids enhance the sense of euphoria and pain-relief but also increases the risk of serotonin syndrome. Serotonin syndrome occurs when there is too much of the neurotransmitter serotonin in the body. If too much serotonin accumulates, it can lead to unconsciousness and death.
The use of ultra-potent opioids with selective serotonin re-uptake inhibitors (SSRIs) and/or monoamine oxidase inhibitors (MAOIs) can also cause serotonin syndrome. Details about serotonin syndrome and its symptoms can be found below.
