Presentation
We present a 20-year-old morphine-addicted man who presented with methadone-induced respiratory depression and responded safely and effectively to intravenous administration of buprenorphine. [ncbi.nlm.nih.gov]
Entire Body System
- Severe Pain
Opioid analgesics are the mainstay of treatment of moderate and severe pain. [ncbi.nlm.nih.gov]
[…] bu·pre·nor·phine | \ ˌbyü-prə-ˈnȯr-ˌfēn, -fən \ : a semisynthetic narcotic analgesic that is administered in the form of its hydrochloride C 29 H 41 NO 4 ·HCl to control moderate to severe pain and treat opioid dependence Note: Buprenorphine is administered [merriam-webster.com]
Additional fetal monitoring may be required in pregnancies complicated by severe pain or opioid addiction on a case-by-case basis. [medicinesinpregnancy.org]
- Weakness
Nociceptin receptor (NOP, ORL-1): Weak affinity. Very weak partial agonist. [en.wikipedia.org]
Overdose symptoms may include extreme drowsiness or weakness, cold or clammy skin, pinpoint pupils, slow heart rate, weak pulse, very slow breathing, or coma. What should I avoid while taking buprenorphine sublingual (Subutex)? Do not drink alcohol. [emedicinehealth.com]
Call your doctor at once or seek emergency medical attention if you have: weak or shallow breathing, feeling like you might pass out; confusion, loss of coordination, extreme weakness ; blurred vision, slurred speech; liver problems --upper stomach pain [rxlist.com]
[…] faintness, or lightheadedness when getting up suddenly from a lying or sitting position drowsiness irregular, fast, slow, or shallow breathing pale or blue lips, fingernails, or skin pinpoint pupils relaxed and calm feeling sleepiness unusual tiredness or weakness [mayoclinic.org]
- Falling
RESULTS: Participants reported high levels of sleep impairment on the MOS, including not getting the amount of sleep they needed (42.9%), not sleeping enough to feel rested (39.6%) and trouble falling asleep (23.3%) or falling back asleep after waking [ncbi.nlm.nih.gov]
If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it. [psychonautwiki.org]
SoberBowl II: Stealth Recovery Advocacy In the fall of 2016, Houston was abuzz with excitement about Super Bowl 2017, which was held at Houston's NRG Stadium. [attcnetwork.org]
- Intravenous Administration
These deaths are generally related to misuse of HDB with intravenous administration and/or concomitant use of benzodiazepines, and they usually occur in patients on HDB substitution therapy for opioid dependence. [ncbi.nlm.nih.gov]
Naloxone has poor bioavailability in the sublingual form; therefore, buprenorphine’s effect predominates. 15, 27 However, if buprenorphine-naloxone is taken inappropriately via subcutaneous, intramuscular, or intravenous administration, sufficient naloxone [cfp.ca]
- Weight Loss
Sometimes weight loss, codependency, problems sleeping, and depression can occur as unwanted side effects of taking buprenorphine. [prescription-drug.addictionblog.org]
If I want to prescribe you Walter-White-level quantities of methamphetamine for weight loss, nothing is stopping me but common sense. [slatestarcodex.com]
loss, and seizures) and death. 11 Methadone-associated NAS often requires prolonged hospitalization, pharmacologic intervention, and monitoring. [nejm.org]
Respiratoric
- Respiratory Distress
Although safe in opioid-naive patients, naloxone may cause severe and even life-threatening complications in opioid-dependent patients, including acute respiratory distress syndrome and myocardial infarction. [ncbi.nlm.nih.gov]
[…] depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus, urinary hesitation, urinary incontinence, urinary retention, urticaria, vasodilatation, vertigo, vision blurred [app.purduepharma.com]
- Respiratory Insufficiency
It must not be used in patients with severe respiratory insufficiency (difficulty breathing) or severe liver problems. [ema.europa.eu]
Gastrointestinal
- Dysphagia
[…] coordination abnormal, dehydration, depersonalization, depressed level of consciousness, depressed mood, disorientation, disturbance in attention, diverticulitis, drug hypersensitivity, drug withdrawal syndrome, dry eye, dry skin, dysarthria, dysgeusia, dysphagia [app.purduepharma.com]
Kopecky, Patients with chronic pain and dysphagia (CPD): unmet medical needs and pharmacologic treatment options, Current Medical Research and Opinion, 30, 12, (2543), (2014). Mark D. Rollins, John R. Feiner, Jessica M. [doi.org]
- Dyspepsia
The common(≥ 1% to < 5%) adverse reactions reported by patients treated with BUTRANS in the clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Gastrointestinal disorders : diarrhea, dyspepsia, and [app.purduepharma.com]
Cardiovascular
- Tachycardia
The most common clinical effects reported in children aged ≤5 years were drowsiness in 105 (58.6%), vomiting in 47 (26.2%), respiratory depression in 34 (19.0%), miosis in 27 (15.1%), agitation in 18 (10.1%), and tachycardia in 15 (8.4%). [cdc.gov]
Signs and symptoms of opioid withdrawal Abdominal Cramping Anorexia Anxiety Diarrhea Dysphoria Elevated Blood Pressure Fatigue Fever Headache Insomnia Lacrimation Muscle Spasms Mydriasis Myalgia Nausea Piloerection Restlessness Rhinorrhea Tachypnea Tachycardia [ncbi.nlm.nih.gov]
[…] muscle weakness, nervousness, nightmare, orthostatic hypotension, palpitations, psychotic disorder, respiration abnormal, respiratory depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia [app.purduepharma.com]
[…] ambulatory patients. 202 214 Potential risk of serotonin syndrome with concurrent use of buprenorphine and other serotonergic agents. 400 Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia [drugs.com]
Jaw & Teeth
Musculoskeletal
- Muscle Spasm
Spasms Mydriasis Myalgia Nausea Piloerection Restlessness Rhinorrhea Tachypnea Tachycardia Vomitting Yawning Since the Harrison Narcotics Act of 1914, office based-treatment of opioid addiction has not been available in the United States ( Table 3 ). [ncbi.nlm.nih.gov]
The buprenorphine in BUTRANS may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. [app.purduepharma.com]
Skin
- Hyperhidrosis
Adverse events most commonly observed with the sublingual administration of buprenorphine during clinical trials and post-marketing experience are headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, and [www2.mallinckrodt.com]
= 392) Placebo (N = 261) Nausea 21% 6% Application site pruritus 15% 12% Dizziness 15% 7% Headache 14% 9% Somnolence 13% 4% Constipation 13% 5% Vomiting 9% 1% Application site erythema 7% 2% Application site rash 6% 6% Dry mouth 6% 2% Fatigue 5% 1% Hyperhidrosis [app.purduepharma.com]
183 184 185 dizziness, 1 2 3 4 9 44 71 99 183 185 vertigo, 1 2 3 nausea. 1 2 3 4 40 44 49 51 53 67 71 76 79 83 93 105 183 184 185 192 Sublingually dissolving strips: Oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis [drugs.com]
- Angioedema
[…] treatment, that were seen in < 1% of the patients in the BUTRANS trials include the following in alphabetical order: Abdominal distention, abdominal pain, accidental injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema [app.purduepharma.com]
[…] seizure disorders. 213 Sensitivity Reactions Hypersensitivity Reactions Acute and chronic hypersensitivity reactions reported. 202 213 Rash, 202 213 214 urticaria, 202 213 214 and pruritus 202 213 214 are most common; 202 213 214 bronchospasm, 202 213 214 angioedema [drugs.com]
- Skin Rash
Effects abdominal pain, changes to periods, constipation, drowsiness, headache, hives, increased sweating, loss of appetite, lowered sex drive, nausea, Pharmacotherapy, skin rashes, tiredness, tooth decay, treat severe pain, vomiting, weight gain, withdraw [adf.org.au]
Immediate action required: Call 999 or go to A&E now if: you get a skin rash that may include itchy, red, swollen, blistered or peeling skin you're wheezing you get tightness in the chest or throat you have trouble breathing or talking your mouth, face [nhs.uk]
- Eruptions
[…] allergic contact dermatitis from transdermal buprenorphine (TDB) in five older patients suffering from chronic pain and who developed persistent, pruritic erythematous plaques at the contact sites, with two of them also presenting with a generalized skin eruption [ncbi.nlm.nih.gov]
Eyes
- Miosis
In the 54 children who developed toxicity, the clinical effects included drowsiness or lethargy (55%), vomiting (21%), miosis (21%), respiratory depression (7%), agitation or irritability (5%), pallor (3%), and coma (2%). There were no fatalities. [pediatrics.aappublications.org]
The authors note that BPN overdose is essentially an opioid overdose, and it produces CNS and respiratory depression, miosis, and occasional vomiting. [journals.lww.com]
[…] the use of buprenorphine are similar to those of other opioids and include: nausea and vomiting, drowsiness, dizziness, headache, memory loss, cognitive and neural inhibition, perspiration, itchiness, dry mouth, shrinking of the pupils of the eyes (miosis [en.wikipedia.org]
The most common clinical effects reported in children aged ≤5 years were drowsiness in 105 (58.6%), vomiting in 47 (26.2%), respiratory depression in 34 (19.0%), miosis in 27 (15.1%), agitation in 18 (10.1%), and tachycardia in 15 (8.4%). [cdc.gov]
Ears
- Tinnitus
nervousness, nightmare, orthostatic hypotension, palpitations, psychotic disorder, respiration abnormal, respiratory depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus [app.purduepharma.com]
Psychiatrical
- Euphoria
This means that, although Buprenorphine is an opioid, and thus can produce typical opioid effects and side effects such as euphoria and respiratory depression, its maximal effects are less than those of full agonists like heroin and methadone. [naabt.org]
Cognitive euphoria - This particular substance can be considered as less intense in its cognitive euphoria when compared with that of morphine or diacetylmorphine (heroin) due to it being a partial agonist of the μ-opioid receptor. [psychonautwiki.org]
When it’s taken in the prescribed doses, Subutex usually does not generate the same level of euphoria, drowsiness or central nervous system suppression as street narcotics. [luxury.rehabs.com]
Being that buprenorphine is an opioid and does cause euphoria, some people may use this drug in a manner other then prescribed and develope a dependency. Thankfully, buprenorphine is easier to manage than other opiate replacement therapies. [drugrehab.org]
- Depersonalization
Kappa receptor activation produces analgesia, miosis, sedation, dysphoria and psychotomimetic effects including disorientation and/or depersonalization. [federalregister.gov]
[…] injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema, apathy, application site dermatitis, asthma aggravated, bradycardia, chills, confusional state, contact dermatitis, coordination abnormal, dehydration, depersonalization [app.purduepharma.com]
Urogenital
- Urinary Retention
This case report illustrates an occurrence of acute urinary retention after initiation of oral buprenorphine/naloxone. [ncbi.nlm.nih.gov]
Side-effects can include and vomiting, drowsiness, dizziness, headache, itch, dry mouth, difficulty ejaculating, decreased sex drive, urinary retention, and constipation. [aidsmap.com]
retention and/or severe constipation, which may lead to paralytic ileus; monitor for signs of urinary retention or reduced gastric motility when buprenorphine is concomitantly used with anticholinergics Serotonergic drugs Opioids may enhance serotonergic [reference.medscape.com]
- Kidney Failure
We describe herein a case of acute liver and kidney failure in a patient with previously latent hepatitis C virus chronic infection following recommended doses of buprenorphine. [ncbi.nlm.nih.gov]
Osborne R, Joel S, Grebenik K et al (1993) The pharmacokinetics of morphine and morphine glucuronides in kidney failure. Clin Pharmacol Ther 54:158–167 PubMed Google Scholar 99. [doi.org]
- Renal Insufficiency
Buprenorphine metabolism is independent of renal function, which is advantageous in renal insufficiency. The risk of respiratory depression after buprenorphine is difficult to quantify. [ncbi.nlm.nih.gov]
Neurologic
- Confusion
Older adults may be more sensitive to the side effects of this drug, especially confusion, dizziness, drowsiness, slow/shallow breathing, and QT prolongation (see above). [webmd.com]
[…] swelling of the face, arms, hands, lower legs, or feet rapid weight gain tingling of the hands or feet unusual weight gain or loss Get emergency help immediately if any of the following symptoms of overdose occur: Symptoms of overdose Blurred vision confusion [mayoclinic.org]
- Tremor
[…] when the hands are outstretched; measured on a scale of 0-4, from no visible tremors, to full twitching of muscles Yawning during assessment; measured from 0-4, from no yawning, to yawning several times per minute Anxiety or irritability; measured from [americanaddictioncenters.org]
[…] withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor [reference.medscape.com]
The symptoms of withdrawal, known as neonatal abstinence syndrome (NAS) include hypersensitivity and hyperirritability, tremors, vomiting, respiratory difficulties, poor sleep, and low-grade fevers. [idpc.net]
Abstinence Syndrome 01:43 The neonatal abstinence syndrome is defined as the occurrence of signs and symptoms of neonatal withdrawal after in utero drug exposure. 1 Among drug exposures, opioids cause severe symptoms, including autonomic instability, tremor [nejm.org]
- Slurred Speech
Call your healthcare provider or get emergency help right away if you: Feel sleepy and uncoordinated Have blurred vision Have slurred speech Cannot think well or clearly Have slowed reflexes and breathing Do not inject (“shoot‐up”) SUBOXONE Film. [suboxone.com]
Call your doctor at once or seek emergency medical attention if you have: weak or shallow breathing, feeling like you might pass out; confusion, loss of coordination, extreme weakness ; blurred vision, slurred speech; liver problems --upper stomach pain [rxlist.com]
Call your doctor at once or seek emergency medical attention if you have: weak or shallow breathing, feeling like you might pass out; confusion, loss of coordination, extreme weakness; blurred vision, slurred speech; liver problems --upper stomach pain [emedicinehealth.com]
Slurred speech, stumbling, or feeling confused, very sleepy or dizzy, or drunk. Not able to focus. [drugs.com]
- Somnolence
Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. [pharmacompass.com]
The most common serious adverse drug reactions (all The most common adverse events (≥ 2%) leading to discontinuation were: nausea, dizziness, vomiting, headache, and somnolence. [app.purduepharma.com]
The most common adverse reactions (≥5%) reported by patients treated with Butrans in clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application [butrans.com]
After a total dose of 5 mg naloxone, the child experienced reversal of somnolence, and maintained a normal respiratory effort. It took about 48 hours for the child's mental status to return to normal. [journals.lww.com]
- Apathy
As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. Buprenorphine is often sold under the brand name Suboxone, which also contains naloxone. [psychonautwiki.org]
[…] were seen in < 1% of the patients in the BUTRANS trials include the following in alphabetical order: Abdominal distention, abdominal pain, accidental injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema, apathy [app.purduepharma.com]
Treatment
In 2000, buprenorphine became the first narcotic drug that could be prescribed by certified physicians for the treatment of opioid dependence under the Drug Addiction Treatment Act. [luxury.rehabs.com]
PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. [ncbi.nlm.nih.gov]
To find treatment go to www.TreatmentMatch.org How buprenorphine works -- Graphics (PDF) NAABT buprenorphine treatment brochure buprenorphine-research U.S. [naabt.org]
[…] if not all addiction treatments in the last 30 years,” added Dr. [drugabuse.com]
Etiology
Regardless of etiology, sleep-disordered breathing and its consequences present unique challenges to the patient in recovery from an opioid use disorder and therefore warrants careful evaluation and management. [ncbi.nlm.nih.gov]
Epidemiology
Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD)-10 and PHQ-2. In addition, information was gathered on participant demographics and treatment characteristics. [ncbi.nlm.nih.gov]
Levels of evidence Level I: At least one properly conducted randomized controlled trial, systematic review, or meta-analysis Level II: Other comparison trials, non-randomized, cohort, case-control, or epidemiologic studies, and preferably more than one [cfp.ca]
Report of the Asian Multi-city Epidemiological Workgroup. Eds. Navaratnam, V. and Bakar, A.A. 144-50. Coggans, N., Shewan, D., Henderson, M; Davies, J.B. (1991). The impact of school-based drug education. Br J Addict. 86:1099-1109. [federalregister.gov]
Ritchie, Pain Behind Bars: The Epidemiology of Pain in Older Jail Inmates in a County Jail, Journal of Palliative Medicine, 17, 12, (1336), (2014). P. D. MacFarlane, A. S. Tute and B. [doi.org]
Pathophysiology
By evaluating the pharmacological characteristics of this substance, as well as the data previously published in the literature, we have attempted to explain the pathophysiological mechanisms of this particular mode of poisoning that can easily be fatal [ncbi.nlm.nih.gov]
‡ Research Fellow, # Professor, Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg. [doi.org]
Prevention
The high affinity also prevents binding of other opioids, at commonly used clinical doses, to receptor sites - preventing their analgesic and likely minimum alveolar concentration (MAC) reducing benefits. [ncbi.nlm.nih.gov]
Severe withdrawal side effects can usually be prevented when a person is switched to buprenorphine and naloxone combination. It acts on the central nervous system (CNS) to help prevent the withdrawal side effects. [mayoclinic.org]