Pharmacodynamics
Tapentadol is a centrally acting synthetic analgesic and NRI (norepinephrine reuptake inhibitor). Its action is approximately one-eighteenth that of morphine and similar to that of tramadol. It binds mainly to the μ-opioid receptor. It also increases the concentration of norepinephrine in the brain through a process called reuptake inhibition. This is the reason why tapentadol, in addition to the analgesic effect, also exerts a pronounced anxiolytic and euphoric effect. The analgesic effect usually occurs after about 30 minutes and usually lasts between 4 and 6 hours.
Pharmacokinetics
Tapentadol is not a prodrug and therefore does not rely on metabolism to exert its therapeutic effect. This makes it an agent of choice for patients who do not respond adequately to more commonly used opioids due to genetic predisposition (slow metabolizers of CYP3A4 and CYP2D6).
Oral bioavailability is approximately 32%. The peak effect is reached after approximately 1.5 hours. Plasma protein binding is about 20% and elimination half-life is about 4 hours.
Drug Interactions
Combination with SSRIs/SNRIs, SRAs, and serotonin receptor agonists may result in potentially fatal serotonin syndrome. Combination with MAOIs can also lead to what is called an "adrenergic storm," a dangerously rapid increase in certain neurotransmitters in the brain.
Taking tapentadol together with sedatives such as benzodiazepines, barbiturates, phenothiazines, and other opiates can lead to increased impairment, sedation, respiratory depression, and in severe cases, death.
The combination of tapentadol and alcohol may result in increased plasma concentrations of tapentadol and cause respiratory depression. Patients should therefore never consume alcohol while taking tapentadol.
Co-administration with anticholinergics should be avoided, if possible, as this may lead to urinary retention and subsequent renal damage.
