Originally posted 1/2/2013
We can now leave naloxone out of the discussion, and focus on the side effects of Suboxone that are caused by buprenorphine.
Side effects are symptoms caused by a given medication that are not part of the therapeutic benefit of that medication. Whether a symptom is a side effect depends on the reason for taking the medication. For example, decreased intestinal motility is the desired effect of opioids used to treat diarrhea, but a bothersome side effect when taking opioids for pain. The term ‘side effect’ is not on the package insert for medication, the symptoms and actions instead referred to as ‘adverse reactions.’ Package inserts also have a section entitled ‘warnings and precautions’ where the most dangerous adverse reactions are listed.
Some medications have a ‘black box warning’ for adverse reactions that are particularly common or particularly dangerous, consisting of a frightening statement at the start of the package insert (enclosed, naturally, by a black box). Black box warnings in psychiatry include the warning for increased suicidal ideation in children and adolescents treated with antidepressants, and the increased risk of death in people with dementia treated with atypical antipsychotics.
Increased risk of cancer or mutations, and effects on fertility or fetal development, are listed in yet another section entitled ‘nonclinical toxicology.’ They are listed as ‘nonclinical’ because the events do not involve the intended physiologic system or pathway targeted by the medication. For example, slowing of intestinal activity by opium is either treatment of diarrhea or unwanted constipation, but in either case the outcome is caused by actions of opioids at opioid receptors. If the opium molecule happened to bind to DNA and cause cancer, the cancer would be nonclinical toxicology, not a side effect. Carbamazepine decreases the excitability of neurons to prevent seizures, and the sedation caused by the slowing of neurons is considered an adverse reaction. Carbamazepine impairs fetal development through different actions, considered nonclinical toxicology.
All of these divisions can be picked apart so that division of symptoms to one category or another will appear arbitrary. The system is not precise, by a long shot. But it may be helpful to be aware that one person’s ‘adverse reactions’ are another person’s intended therapeutic effect. Some people find the mood stabilizer quetiapine too sedating; others find the sedation critical to a good night’s sleep.
Allergic reactions are yet another issue. To put it simply, medication allergies are not something that the medication does to the body, but rather something that the body (the immune response) does to a medication—and the inflammatory fall-out from that reaction. While the distinction sounds like splitting hairs, the true nature of a reaction can be important. Nausea is a common adverse event from the action of opioids, used for pain control, at opioid receptors. Through intellectual laziness, a patient with nausea from morphine in a hospital is often incorrectly labeled as having a morphine allergy. Because of the bureaucracy of modern medicine, the patient has had a very useful medication removed from the armamentarium of treatment options, in essence forever. Analogous situations are ‘allergies’ to antibiotics like erythromycin. Allergies tend to become worse with each medication exposure, whereas adverse reactions often go away over time.
Am I going to need a part 3?
Things actually get pretty simple from here. Buprenorphine, like other opioids, has a range of predictable effects that occur along the dosage spectrum— a spectrum that is relative to the person’s opioid tolerance. Doses of buprenorphine low on the person’s tolerance spectrum fail to have the desired action of preventing withdrawal. Doses that are close to a person’s tolerance level have the desired therapeutic effect, i.e. blocking withdrawal and a reduction in cravings for opioids. Doses in this range commonly cause ‘ileus’, i.e. disruption of the normal movement of the intestine. Ileus in turn causes a number of symptoms, including constipation, cramping, bloating, loss of appetite, and nausea. Constipation can lead to increased intestinal pressure, leading to hemorrhoids or diverticular disease.
Apart from ileus, buprenorphine and all opioids have direct actions at the base of the brain, at the ‘area postrema’. Actions at the area postrema cause nausea as an adverse reaction, or in other cases the desired therapeutic effect of induced vomiting. Nausea is very common when doses of opioids are taken that are at the upper end of tolerance, making nausea particularly common with potent opioids like buprenorphine. Impaired coordination, slow reflexes, sedation, slurred speech, and somnolence are also caused by strong opioid effects. Combinations of these effects are obviously quite dangerous.
Opioids reduce the tone of the ‘gastroesophageal sphincter’, increasing the chance of acid reflux, heartburn, hoarseness, and theoretically even esophageal cancer in severe cases.
Cough suppression by opioids might be a therapeutic benefit, but can be an adverse reaction if gastric contents are aspirated into the lungs.
Opioids reduce the response of the brain’s respiratory centers to carbon dioxide, resulting in less drive to breathe. Carbon dioxide level therefore goes up, and the rise in CO2 increases brain blood volume and in turn, intracranial pressure. The increased brain pressure reduces the flow of fresh, oxygenated blood into the brain. Because of this potentially-disastrous sequence of events, opioids must be used with caution in people with head injuries.
Respiratory depression is a common reason for overdose, but even that adverse event can be a desired therapeutic benefit in some cases, for example in patients who are on a ventilator and triggering the machine to cause hyperventilation. Respiratory depression is even used therapeutically to reduce ‘air hunger’ in people at the end of their lives, to relieve suffering in patients and patients’ family members who are witnessing the death.
I realize that a simple list of side effects would have been easier to read, but like the proverb says about giving a man a fish, I’m hoping that running through the processes will help people figure out, for themselves, what their medications are doing.
What else… pruritis or ‘itching’ is a common side effect of potent opioids, that doesn’t respond very well to the usual anti-itching treatments like diphenhydramine or steroids. All common opioids except meperidine (Demerol) constrict pupils, which often makes daytime vision sharper, but impairs night vision by allowing less light to fall on the retina.
Opioids reduce immune function through a number of physiologic interactions, including the presence of opioid receptors on immune tissue. Opioids can have a range of effects on mood and mood disorders. All opioids, including buprenorphine, have the potential to reduce testosterone levels in men, which in turn can affect mood, libido, and sexual performance. Opioids alter the release of vasopressin, changing how much water is conserved by our kidneys—which in some people results in more trips to the bathroom at night.
Buprenorphine and other potent opioids interfere with the initiation of ‘micturition’, i.e peeing, particularly in men who are already struggling from an enlarged prostrate.
I know that I’m missing something, and I invite people to write and help me out. I also realize, as I write this, that I don’t have a package-insert category for a particularly common worry about Suboxone, that it is hurting one’s teeth. Such a reaction, were it found to be attributable to Suboxone, would probably be considered nonclinical toxicology, although a recent case report proposed that buprenorphine could increase cavities by reducing the immune response in teeth, which sounds more like an adverse reaction. In either case, I’ve written about the lack of evidence for tooth damage from Suboxone, but the topic still appears on my forum now and then.
That’s all for now…
Originally posted 1/2/2013