Tapentadol

Tapentadol is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the mu-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). It is used in the management of moderate to severe pain. Tapentadol was approved by the United States Food and Drug Administration (FDA) in November 2008, for the treatment of moderate to severe acute pain. Extended-release formulations are available for the management of chronic pain that requires continuous, long-term treatment.

Pharmacology

Tapentadol acts primarily through two mechanisms: as a mu-opioid receptor agonist and as a norepinephrine reuptake inhibitor. Unlike traditional opioids, which exert their analgesic effects primarily through opioid receptor agonism, tapentadol's additional mechanism of norepinephrine reuptake inhibition allows for a synergistic effect in pain relief, potentially reducing the need for higher opioid doses and thereby mitigating opioid-related side effects.

Mechanism of Action

The analgesic properties of tapentadol are due to its dual action. The mu-opioid receptor agonism provides direct pain relief by acting on the central nervous system, while the inhibition of norepinephrine reuptake enhances analgesia through the modulation of the descending pain inhibitory pathway. This dual mechanism allows tapentadol to be effective in the treatment of pain with both nociceptive and neuropathic components.

Pharmacokinetics

Tapentadol is well absorbed after oral administration, with an oral bioavailability of approximately 32% due to first-pass metabolism. It reaches peak plasma concentrations within 1.25 to 1.5 hours. Tapentadol is metabolized in the liver primarily through phase 2 pathways, including glucuronidation, and is excreted predominantly in the urine. The half-life of tapentadol is about 4 hours, necessitating multiple doses per day for the management of chronic pain.

Clinical Use

Tapentadol is indicated for the relief of moderate to severe acute pain in adults. It is also available in an extended-release formulation, which is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Contraindications

Tapentadol is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, and in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

Side Effects

Common side effects of tapentadol include nausea, vomiting, dizziness, somnolence, and headache. As with other opioids, there is a risk of respiratory depression, particularly when initiating treatment or increasing the dose. Tapentadol may also increase the risk of seizures, especially in patients with a history of seizure disorders or when taken with other drugs that lower the seizure threshold.

Regulatory Status

Tapentadol is classified as a Schedule II controlled substance in the United States, indicating a high potential for abuse and dependence. Its approval and use are also regulated in many other countries, with varying schedules and restrictions.

See Also

• Opioid epidemic
• Pain management
• Norepinephrine reuptake inhibitor
• Mu-opioid receptor