Buprenorphine

Buprenorphine, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal), or as an implant.[19]

In the United States, the combination formulation of buprenorphine/naloxone (Suboxone) is usually prescribed to discourage misuse by injection. Maximum pain relief is generally within an hour with effects up to 24 hours. Buprenorphine affects different types of opioid receptors in different ways. Depending on the type of opioid receptor, it may be an agonist, partial agonist, or antagonist. Buprenorphine's activity as an agonist/antagonist is important in the treatment of opioid use disorder: it relieves withdrawal symptoms from other opioids and induces some euphoria (primarily when first starting treatment if one is not already opioid tolerant/dependent), but also blocks the ability for many other opioids, including heroin, to cause an effect. Unlike full agonists like heroin or methadone, buprenorphine has a ceiling effect, such that taking more medicine past a certain point will not increase the effects of the drug.[20]

Being a partial MOR agonist, buprenorphine offers flexibility to prescribers treating opioid use disorder as the dosage can be easily adjusted.

Side effects may include respiratory depression (decreased breathing), sleepiness, adrenal insufficiency, changes in heart electrophysiology (QT prolongation), low blood pressure, allergic reactions, constipation, and opioid addiction.[21] Among those with a history of seizures, a risk exists of further seizures. Opioid withdrawal following stopping buprenorphine is generally less severe than with other opioids. Whether use during pregnancy is safe is unclear, but use while breastfeeding is probably safe, since the dose the infant receives is 1–2% that of the maternal dose, on a weight basis.[22]

Buprenorphine was patented in 1965, FDA approved for medical use as an analgesic in 1981, and FDA approved for treating opioid use disorder in 2002.[23][24] It is on the World Health Organization's List of Essential Medicines.[25] Despite originally being marketed as an analgesic it is far more commonly prescribed and used to treat opioid use disorders, such as addiction to heroin.[26] In 2020, it was the 186th most commonly prescribed medication in the United States, with more than 2.8million prescriptions.[27][28]

Buprenorphine is generally used as a medication for treating opioid use disorder. In the United States, buprenorphine hydrochloride (and a combination formula, buprenorphine hydrochloride/naloxone,) are schedule III controlled substances.

Buprenorphine does not produce the same sense of euphoria and/or "sense of well-being" as reported in use of full-agonist opioids. A "ceiling effect"[29] is observed in regards to the potentially fatal side effects of other opioids, such as respiratory depression. While the medication may produce comparably mild side effects to that of other drugs in its classification, it still carries some abuse potential.

Medical uses

Adverse effects

Common adverse drug reactions associated with the use of buprenorphine, similar to those of other opioids, 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), orthostatic hypotension, male ejaculatory difficulty, decreased libido, and urinary retention. Constipation and central nervous system (CNS) effects are seen less frequently than with morphine.[52] Central sleep apnea has also been reported as a side effect of long-term buprenorphine use.[53][54]

Pharmacology

Chemistry

Buprenorphine is a semisynthetic derivative of thebaine,[96] and is fairly soluble in water, as its hydrochloride salt. It degrades in the presence of light.

History

In 1969, researchers at Reckitt and Colman (now Reckitt Benckiser) had spent 10 years attempting to synthesize an opioid compound "with structures substantially more complex than morphine [that] could retain the desirable actions whilst shedding the undesirable side effects". Physical dependence and withdrawal from buprenorphine itself remain important issues since buprenorphine is a long-acting opioid.[98] Reckitt found success when researchers synthesized RX6029 which had shown success in reducing dependence in test animals. RX6029 was named buprenorphine and began trials on humans in 1971.[99][100] By 1978, buprenorphine was first launched in the UK as an injection to treat severe pain, with a sublingual formulation released in 1982.

Society and culture

Research

Veterinary use

Buprenorphine is commonly used as a long-lasting post-operative analgesic in small animal veterinary practice. Buprenorphine can be administered via subcutaneous, transdermal, intravenous, or intramuscular. Buprenorphine provides analgesia for 6–8 hours in dogs and 4–8 hours in cats when administered as an intramuscular or intravenous injection. Buprenorphine as a partial agonist of the mu-receptor has less adverse effects than full agonists. A transdermal application can provide analgesia for up to 4 days in cats. The oral-transmucosal route has been investigated due to the potential for client administration but variability in bio-availability and other issues limit this usage. When used in combination with local anaesthetics or a non-steroidal anti-inflammatory drug buprenorphine provides good analgesia for ovariohysterectomies and orchidectomies. In horses buprenorphine can be used for castration and dental extraction; however, buprenorphine is not commonly used in horses as a post-operative analgesic due to potential for adverse gastrointestinal effects and locomotive stimulation. Buprenorphine is commonly given alongside acepromazine or a2 adrenergic receptor agonists[128][129]

External links