Buprenorphine

The active ingredient buprenorphine is a semisynthetic pharmaceutical belonging to the group of opioid receptor agonists (opioids) derived from the opium alkaloid thebaine. Its good safety profile makes it the drug of choice for severe chronic pain. In high doses, it can also help with opioid withdrawal.

Buprenorphine has a partial agonist effect with high affinity to the µ-opioid receptors (mediating effects such as euphoria, analgesia, respiratory depression and dependence) and an antagonist effect at the kappa receptor (mediating effects such as dysphoria and sedation). Compared to methadone and heroin, buprenorphine thus shows important differences from other opioids due to its specific properties at the opioid receptors: buprenorphine has a higher receptor affinity than heroin and methadone. Buprenorphine is not a so-called full agonist (where the effect increases with increasing dosage), but a partial agonist.

In contrast to the other active substances, it shows a so-called "ceiling effect", e.g. for respiratory depression (there is no linear dose-response relationship). With increasing dosage, a plateau of effect is reached). However, this phenomenon is only observed at very high doses, well outside the analgesic range. This effect is particularly important for addiction withdrawal, as it effectively alleviates withdrawal symptoms, but does not lead to dose increases and overdoses.

In the therapeutically relevant dosage range (0.2 to 7 mg), however, the opioid behaves as a pure agonist. This means that dose increases always cause an increase in analgesia. Thus, buprenorphine achieved full efficacy not only in acute pain models but also in experiments on inflammatory, neuropathic and visceral pain.

Buprenorphine is degraded in the liver via cytochrome P450 3A4. With concomitant use of enzyme inducers (e.g.(carbamazepine, phenytoin, phenobarbital, rifampicin) buprenorphine can be degraded at an accelerated rate.

Depending on the dosage form, absorption occurs either via the skin (patches) or the mucous membranes (sublingual tablets). Via the mucous membranes, the active substance reaches the highest blood levels after about one and a half hours. Via the patch, the active substance buprenorphine enters the body more slowly and reaches effective concentrations in the blood after four to twelve hours, but the maximum values only after about one and a half days. About two-thirds of buprenorphine is excreted unchanged in the bile via the intestines, and one-third is broken down in the liver and excreted in the urine. The duration of action of buprenorphine after sublingual administration is 6 to 8 hours. The dependence potential is comparatively low.

Buprenorphine is used on the one hand for pain therapy and on the other hand for withdrawal in the treatment of opioid dependence. Compared to the opiate morphine, the active ingredient buprenorphine has an approximately 25 to 50 times greater potency. Buprenorphine is considered a first-line agent for the treatment of severe chronic pain in the elderly due to its good safety profile. Buprenorphine is available as a transdermal patch and as a sublingual preparation.

Buprenorphine should not be taken during pregnancy and breastfeeding, as the active substance can enter the child's circulation to a greater extent, especially when taken shortly before birth and during breastfeeding. This can lead to "floppy infant syndrome", whereby the newborn or infant shows hardly any body tension, reacts little to its environment and breathes shallowly, which can sometimes be life-threatening.

Common dosages range from 0.2 to 0.4 mg of buprenorphine every six to eight hours. Buprenorphine patches are applied for several days (varies by manufacturer, usually three to four days) and continuously release buprenorphine through the skin into the body. This delivery method is often chosen for longer-term therapy.

Temgesic®;: Bunalict® 2 mg/0.5 mg sublingual tablets; Subutex®, buprenorphine mepha®; TRANSTEC®;

Antidote for overdose: Naloxon.

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