Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

@article{Miotto2017TrendsIT,
  title={Trends in Tramadol: Pharmacology, Metabolism, and Misuse.},
  author={Karen Miotto and Arthur K. Cho and Mohamed A. Khalil and Kirsten Blanco and Jun D Sasaki and Richard Rawson},
  journal={Anesthesia \& Analgesia},
  year={2017}
}
Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic… 
View on Wolters Kluwer
ncbi.nlm.nih.gov
182 Citations
Highly Influential Citations
9
Background Citations
56
Results Citations
2

Figures and Tables from this paper

182 Citations

Citation Type

Citation Type

ADME and toxicity considerations for tramadol: from basic research to clinical implications
TLDR
This review provides a comprehensive view on the pharmacokinetic, pharmacodynamic, and toxicity of tramadol with a deep look on its side effects, biochemical and pathological changes, and possible drug interactions.
CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia
TLDR
The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse.
Tramadol for the Management of Opioid Withdrawal: A Systematic Review of Randomized Clinical Trials
TLDR
The results showed that it exhibits better efficacy and tolerance with fewer side effects in specific clinical scenarios as compared to existing available detox management, and was considered a viable replacement for some of these treatment regimes.
Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures.
Clinically significant drug-drug interactions between tramadol and CYP3A4 inhibitors: disproportionality analysis in VigiBase® and hypothesis on the underlying mechanism
TLDR
It is postulate that tramadol-induced psychotic disorders would not be caused by the ODMT but rather by the serotoninergic action of tramadl itself, and concurrent use of tramADol and CYP3A4 inhibitors should theoretically increase the synaptic serotonin concentration.
Tramadol Use in Perioperative Care and Current Controversies
TLDR
The aim of this review is to discuss the use of tramadol in the perioperative period and to understand the pharmacokinetics and pharmacodynamics in order to provide patients with the safest and most effective analgesia.
Preclinical assessment of tramadol abuse potential: Effects of acute and repeated tramadol on intracranial self-stimulation in rats
TLDR
Tramadol has lower abuse potential than other abused MOR agonists and that repeated tramadol exposure produces relatively little enhancement of abuse potential of other MOR agonist candidates.
Association between opioid use disorder (tramadol) and serum level of interleukin-2
TLDR
It was found that patients with opioid use disorder (tramadol) have significantly elevated serum levels of IL-2 than healthy controls, and this elevation was dose related.
Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice
TLDR
It is demonstrated that long-term tramadol abuse can result in oxidative damage, inflammation, and disruption of the GABA neurotransmitter system, which will help to elucidate the toxicology of tramadl abuse.
Tramadol/Diclofenac Fixed-Dose Combination: A Review of Its Use in Severe Acute Pain
TLDR
Evidence of the efficacy and safety of tramadol/diclofenac FDC for treatment of patients with acute severe pain, including musculoskeletal pain, postoperative pain, and acute flare-up of osteoarthritis or rheumatoid arthritis, appears to be substantial.
...
...

References

SHOWING 1-10 OF 73 REFERENCES
Clinical Pharmacology of Tramadol
TLDR
Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain.
Aspects of tramadol and ondansetron interactions
Effects of the CYP2D6 Gene Duplication on the Pharmacokinetics and Pharmacodynamics of Tramadol
TLDR
Tramadol may frequently cause adverse effects in southern European and Northern African populations with a high proportion of UMs; nevertheless, UMs were more sensitive to tramadol than EMs.
Abuse liability and reinforcing efficacy of oral tramadol in humans.
Rifampicin markedly decreases the exposure to oral and intravenous tramadol
TLDR
Rifampicin markedly decreased the exposure to tramadol and M1 after both oral and intravenous administration and may have a clinically important interaction with tramADol regardless of the route of its administration.
Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users.
  • J. Zacny
  • Psychology, Medicine
    Drug and alcohol dependence
  • 2005
Possible Serotonin Syndrome Associated with Tramadol and Sertraline Coadministration
TLDR
Clinicians should be aware of the potential for serotonin syndrome with concomitant administration of sertraline and tramadol.
Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication
TLDR
CYP2D6 genotypes predicting ultrarapid metabolism resulted in about 50% higher plasma concentrations of morphine and its glucuronides compared with the EM, and it might be good if physicians would know about the CYP2D 6 duplication genotype of their patients before administering codeine.
The Analgesic Efficacy of Tramadol is Impaired by Concurrent Administration of Ondansetron
TLDR
The hypothesis that the tramadol requirement by patient-controlled analgesia (PCA) may be increased when ondansetron is administered for antiemetic prophylaxis is tested.
Antagonistic effects of ondansetron and tramadol? A randomized placebo and active drug controlled study.
...
...