Buprenorphine chemical structure
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Buprenex

Buprenorphine, also colloquially referred to as bupe, is an opioid drug with partial agonist and antagonist actions. Buprenorphine hydrochloride was first marketed in the 1980s by Reckitt & Colman (now Reckitt Benckiser) as an analgesic, yet is now primarily used for the treatment of opioid addiction. It is a Schedule III drug under the Convention on Psychotropic Substances. more...

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Commercial preparations

Britsh firm Reckitt & Colman (now Reckitt Benckiser) first marketed buprenorphine under the trade names Temgesic (sublingual/parenteral preparations, no active additives) and Buprenex (parenteral, no active additives). Two more recent formulations from Reckitt Benckiser have been approved for opioid addiction treatment in the U.S.: Subutex (lemon-lime flavored sublingual, no active additives; in 2mg and 8mg dosages) and Suboxone (orange-tang flavored sublingual, one part naloxone for every four parts buprenorphine; hexagon shaped tablet in 2mg and 8mg dosages). Suboxone contains the opioid antagonist naloxone to deter illicit intravenous preparation of the tablet, this is intended to attenuate the effects of buprenorphine on opioid-naive users should this formulation be injected - however no human studies have been done demonstrating the efficacy of this approach with buprenorphine and a growing number of street reports indicate that the naloxone is ineffective. It must also be noted that buprenorphine in and of itself will induce a precipitated withdrawal syndrome if ingested by an acutely opioid dependent individual via any route.

Buprenorphine is also delivered transdermally in 25, 50 and 75 mcg/hour. The trade name in the UK is Transtec, and manufactured by Napp. A new 5, 10 and 20 mcg/hour patch marketed as Bu'7rans (Bu-trans), where the 7 indicates its once weekly dosage for pain in osteoarthritis.

Pharmacology and pharmacokinetics

Buprenorphine is a thebaine derivative, and its analgesic effect is due to partial agonist activity at μ-opioid receptors. The partial agonist activity means that opioid receptor antagonists (e.g. naloxone) only partially reverse the effects of buprenorphine. Buprenorphine is also a κ-opioid receptor partial agonist/antagonist, and partial/full agonist at the recombinant human ORL1 nociceptin receptor. (Huang et al., 2001)

Buprenorphine hydrochloride is administered by intramuscular injection, intravenous infusion, via a transdermal patch, or as a sublingual tablet. It is not administered orally, due to very high first-pass metabolism. Buprenorphine is metabolised by the liver, via the CYP3A4 isozyme of the cytochrome p450 enzyme system, into norbuprenorphine (by N-dealkylation) and other metabolites. The metabolites are further conjugated with glucuronic acid and eliminated mainly through excretion into the bile. The elimination half-life of buprenorphine is 20.4–72.9 hours (mean 34.6).

The main active metabolite, norbuprenorphine, is a δ-opioid receptor and ORL1 receptor agonist, μ- and κ-opioid receptor partial agonist. (Huang et al., 2001)

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Sorting out opioids
From Nursing, 10/1/01 by McCaffery, Margo

Controlling Pain

QUESTION: I care for many patients with moderate to severe pain. With so many opioids available, how can I determine which type suits a patient best? ANSWER: Understanding how and why each opioid type works will help you make the best choice for your patient. Opioids available in the United States fall into two main groups: the morphine-like mu agonists (also called pure or full agonists) and agonist-antagonists. An agonist is a drug that binds to one of the opioid receptor sites involved in analgesia (mu, delta, or kappa). An antagonist also binds to an opioid receptor, but without causing analgesia. Because it competes with an agonist for the binding site, an antagonist reduces the agonist's ability to provide analgesia. A closer look at mu agonists The largest and most commonly prescribed group of opioids, mu agonists are the mainstay of analgesia for moderate to severe acute pain, breakthrough pain (intermittent episodes of increased pain), and cancer pain, and are increasingly used for chronic nonmalignant pain.

Mu agonists have no ceiling on their analgesia and produce comparable analgesia if doses are adjusted appropriately. However, certain mu agonists such as meperidine should be avoided because of active metabolites. Others, such as codeine, should be reserved for mild to moderate pain only because of adverse effects at higher doses.

Combining a mu agonist with a nonopioid or adjuvant analgesic can improve pain control and may allow a reduction in opioid dose, thus minimizing opioid-related adverse effects, such as oversedation, respiratory depression, and constipation.

Using agonist-antagonists

Agonist-antagonists aren't recommended as first-line drugs for pain. Drawbacks include limited routes of administration and a ceiling for pain relief. Once the analgesic ceiling is reached, dosage increases won't increase analgesia, so these drugs aren't appropriate for severe, escalating pain. They also may reverse the analgesia of mu agonists or precipitate withdrawal in patients who are physically dependent on mu agonists.

Agonist-antagonists can be subdivided into two groups: mixed agonist-antagonists, such as butorphanol (Stadol) and pentazocine (Talwin), and the only partial agonist available in the United States, buprenorphine (Buprenex).

Administer opioids by the least invasive and safest route that's effective. The dose should be titrated to achieve effective pain relief with minimal or acceptable adverse effects. If the patient has unacceptable and unmanageable adverse effects, switch to another opioid. As a rule, use only one route of opioid administration at a time; make the oral route your first choice, when possible, because of its safety, convenience, and price.

SELECTED REFERENCE

McCaffery, M., and Pasero, C.: Pain: Clinical Manual, 2nd edition. St. Louis, Mo., Mosby, Inc., 1999.

BY MARGO MCCAFFERY, RN, MS, FAAN

Consultant in the Nursing Care of Patients with Pain * Los Angeles, Calif.

Copyright Springhouse Corporation Oct 2001
Provided by ProQuest Information and Learning Company. All rights Reserved

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