Clinical Pharmacology of Tramadol

  title={Clinical Pharmacology of Tramadol},
  author={Stefan Grond and Armin Sablotzki},
  journal={Clinical Pharmacokinetics},
Tramadol, a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol and the metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the μ. opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (−)-tramadol inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the… 
Trends in Tramadol: Pharmacology, Metabolism, and Misuse.
This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.
Discovery and development of tramadol for the treatment of pain
The combination of monoamine and opioid mechanisms opens new avenues for the design of innovative analgesic drugs to treat moderate to severe pain.
Tramadol extended-release formulations in the management of pain due to osteoarthritis
Tramadol once-daily formulations are more effective than placebo and at least as effective and well tolerated as immediate-release formulations in the treatment of pain due to osteoarthritis, and offer a reduced dosing regimen, which is especially valuable in elderly patients.
Tramadol: keep calm and carry on
The USA Food and Drug Administration issued a warning in 2013 concerning the use of codeine in children after adenotonsillectomy surgery following a number of deaths that were attributed to overdoses associated with undiagnosed ultra-rapid polymorphisms of CYP2D6.
Extended-release Tramadol (ULTRAM ER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain.
  • R. Barkin
  • Medicine
    American journal of therapeutics
  • 2008
Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors.
Conception and evaluation of tramadol hydrochloride as extended release drug delivery
Tramadol, a synthetic opioid of the amino cyclohexanol group, is a centrally acting analgesic with weak opioid agonist properties the half-life of the drug is about 5.5 hours and the usual oral
Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment
Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol and suggest that both mu and non-mu opioid actions play a role in tramadl’s subjective profile of action.
Extended-release formulations of tramadol in the treatment of chronic pain
Extended-release formulations of tramadol seem to offer a rational and important addition to the analgesic armamentarium, and the benefits and risks must be assessed for each patient.
Comparative metabolism of tramadol and tapentadol: a toxicological perspective
A thorough knowledge about tramadol and tapentadol metabolomics is expected to provide additional insights to better understand the interindividual variability in their pharmacokinetics and dose-responsiveness, and contribute to the establishment of personalized therapeutic approaches, minimizing side effects and optimizing analgesic efficacy.


Tramadol: a review of its use in perioperative pain.
The efficacy of tramadol for the management of moderate to severe postoperative pain has been demonstrated in both inpatients and day surgery patients and, unlike other opioids, tramdol has no clinically relevant effects on respiratory or cardiovascular parameters.
[Duality of the analgesic effect of tramadol in humans].
It is concluded that tramadol analgesia is only partially mediated by a mu opioid agonist effect, which results from an action on opioid receptors other than the mu subtype and/or from nonopioid effects (monoaminergic system).
[Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine].
Investigation of the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain found it to be better tolerated than buprenorphine, and caused fewer and milder adverse reactions.
Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers.
The role of tramadol in each death is explored and an analytical method using gas chromatography-mass spectrometry (GC-MS) without derivatization for the determination of tramadol and its metabolites is reported.
Oral tramadol, a μ-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain
In certain cancer patients with strong pain, tramadol achieved good pain control with fewer side-effects than morphine, suggesting the non-opioid mode of action may result in a different spectrum of analgesia and side- effects.
Serum concentrations of tramadol enantiomers during patient-controlled analgesia.
The therapeutic serum concentration of tramadol and M1 showed a great variability, and was in agreement with the clinical finding that (+)-tramadol is a more potent analgesic than (-)-tamadol.
The Analgesic Efficacy of Tramadol is Impaired by Concurrent Administration of Ondansetron
The hypothesis that the tramadol requirement by patient-controlled analgesia (PCA) may be increased when ondansetron is administered for antiemetic prophylaxis is tested.
Analgesic oral efficacy of tramadol hydrochloride in postoperative pain
Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen‐propoxyphene combination.
Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy
The data demonstrate that kindling enhances the susceptibility of rats to convulsant adverse effects of tramadol and its enantiomers, indicating that a preexisting lowered seizure threshold increases the risk of tramadol‐induced seizures.
Contribution of monoaminergic modulation to the analgesic effect of tramadol.
1. In humans, the central analgesic effect of tramadol 100 mg orally is only partially reversed by the opioid antagonist naloxone (0.8 mg intravenously). As suggested by in vitro and animal data