Blockade Effect and Opioid Withdrawal
The Suboxone preparation contains the μ-opioid receptor antagonist naloxone. Buprenorphine itself is a mixed agonist/antagonist, and, as such, buprenorphine blocks the activity of other opiates and induces withdrawal in opiate dependent individuals who are currently physically dependent on another opiate. It is suggested that a person should wait until withdrawal symptoms begin before starting Suboxone.
Buprenorphine itself binds more strongly to receptors in the brain than do other opioids, making it more difficult, regardless of the presence of the naloxone, to become intoxicated via other opioids when buprenorphine is in the system. If >32mg buprenorphine is in the system, however, it becomes a full agonist; i.e., it not only completely or nearly completely blocks or reverses opiate effects from other opioids, but also itself, causing full withdrawal symptoms. 0.3 mg of buprenorphine parenterally is equivalent in antagonistic effect to between 0.4 and 2.0 mg of naloxone parenterally, but with a much longer half-life. Methadone also blocks the effects of other opioids at higher doses; however, under ~40 mg, the block in effects is barely present. At commonly used methadone maintenance doses, the degree of blockade is similar to that produced by equivalent buprenorphine doses. The blockade effect also has the result of blocking endogenous endorphins from binding to receptors, which can lead to psychological alterations in mood and mental capacity. This can cause cognitive and memory deficiencies via blockade of the reward system, which is pertinent to memory formation and normal mental function. Unlike buprenorphine, however, this is not due to opiate antagonist-like action. Instead, daily use of methadone, like daily use of any of the opiate agonists, results in tolerance to all opiates, called "cross-tolerance". However, it is still possible to use other opioids on either treatment regime, although many people find "getting high" to be difficult or unattainable.
Switching to buprenorphine from methadone is often difficult and withdrawals lasting several days or more are often encountered mostly when the methadone dose is any higher than 30 mg/day (the suggested and usual dose for switching to buprenorphine). A 30 mg dose of methadone is relatively low, and some patients have difficulty reaching that dose, for a variety of reasons, usually the emergence of withdrawal symptoms. Healthy users of methadone who commit to a slow taper, however, frequently find success in tapering to 30 mg in order to switch to buprenorphine, as well as in tapering off of methadone completely without the use of buprenorphine. Switching to buprenorphine at higher doses of methadone may be uncomfortable for the user. One reason is that users must be in withdrawal before switching to buprenorphine, and users of opiates with long half-lives, like methadone, may need to wait several days after their last dose of methadone before they are fully in withdrawal and ready to begin buprenorphine. Users of heroin, hydrocodone, oxycodone, and morphine, as well as most other common opiates, need to wait a maximum of only twenty-four hours before they are fully in withdrawal and ready to begin buprenorphine. For this reason, some doctors switch methadone users to a shorter-acting opiate, such as morphine, for a few days before allowing withdrawal to occur and beginning buprenorphine. On the other hand, switching from buprenorphine to methadone is relatively easy as methadone is a full opiate agonist that does not have a ceiling, and can stop the withdrawal symptoms of users at any dosage of other opiates, including buprenorphine.
There is a common misconception that naloxone, a potent opioid antagonist included in the Suboxone formulation, is active and responsible for this blockade effect. This is not true. Instead, Buprenorphine alone is responsible for the blockade effect due to its high binding affinity at the brains opioid receptors, a higher affinity than that of naloxone. The naloxone is in effect not active regardless of the route of administration.
Read more about this topic: Buprenorphine, Clinical Use
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