Myth Number 6: Opioids do not work for neuropathic pain
Studies have rebutted the above statement, showing that certain unique opioids, such as methadone, levorphanol, tramadol and tapentadol, have a benefit in the treatment of neuropathic pain.
All 4 of these drugs show opioid agonist activity, classifying them as opioid drugs. However, each of these medications also exhibits an additional unique mechanism of action that becomes useful in the treatment of neuropathic pain.
Methadone and levorphanol antagonize both N-methyl-D-aspartate (NMDA) receptors and inhibit norepinephrine reuptake. NMDA receptor antagonists, such as memantine, ketamine, orphenadrine and others, have been shown to successfully treat neuropathic pain. These studies suggest that if a pure NMDA antagonist, such as ketamine, can improve Neuropathic pain, medications such as methadone and levorphanol should have similar benefits.
Tramadol and tapentadol inhibit norepinephrine reuptake. Norepinephrine has been demonstrated in non-opioid drugs, including the serotonin-norepinephrine reuptake inhibitor, duloxetine, to play a role in the treatment of neuropathic pain. The role of Norepinephrine in the treatment of norepinephrine Neuropathic pain was demonstrated by Max et al. In that study, patients with neuropathic pain had better pain relief when treated with desipramine and amitriptyline, compared with fluoxetine or placebo, whose efficacy was attributable to blockade of noradrenergic reuptake.
These results may also be applied to opioid drugs that have norepinephrine activity in the treatment of neuropathic pain. Therefore, atypical opioids with multimodal mechanisms of action should be safely used in the treatment of neuropathic pain.
This does not respond, however, if drugs such as morphine and oxycodone are ineffective for neuropathic pain. We do not believe that opioid monotherapy is appropriate or especially effective for neuropathic pain. Clinically, we have observed that opioid monotherapy seems to be effective temporarily (a few months), but tolerance develops much faster than it should, and doses tend to escalate much faster than when these agents are used for pain Or musculoskeletal. TA) administers a high-risk clinic where the majority (90%) of patients with high doses of opiates (> 300 mg / day MEDD) have experienced dose escalation in an attempt to control an element of neuropathic pain.
Myth Number 7: Tapentadol Increases Risk of Serotonin Syndrome
The usefulness of compounds that block the reuptake of norepinephrine has already been identified as beneficial in the treatment of chronic pain.49 Tapentadol has two mechanisms of action: the opioid agonist and the norepinephrine reuptake inhibitor. Both mechanisms allow tapentadol to provide benefits to patients with neuropathic pain.50,51 Unlike tramadol, which inhibits norepinephrine and serotonin reuptake, tapentadol has a limited interaction with serotonin transporter proteins and minimal effect on Reuptake of serotonin. A compound without serotonergic activity would be at no risk of contributing to serotonin syndrome.52 Therefore, the risk of serotonin syndrome is drastically reduced and almost non-existent with the use of tapentadol.53
The booklet states: “Serotonergic syndrome, potentially life-threatening, has occurred with the concomitant use of tapentadol and serotonergic agents or agents that impair serotonin metabolism.” But these are reports from post-marketing case studies and therefore do not have a black box. Warning for serotonin syndrome.54 A study by Nossaman et al indicates that there is a risk of serotonin syndrome with tramadol and tapentadol; However, the 8 studies referenced to make this claim include the use of tramadol, not tapentadol.55 Although the prospect for tapentadol warns against serotonin syndrome, the simple fact is that the evidence lacks both chemically and clinically .
Myth Number 8: Methadone is a long-acting opioid
As noted above, methadone has both opioid receptor agonist activity and NMDA receptor antagonist activity, creating a distinct pharmacological profile. Methadone has been shown to be useful in the treatment of chronic pain and neuropathic pain and has a role in the medical management of substance use disorders.56 However, the unique pharmacokinetic properties of methadone present dosing and titration challenges Many prescribers.
Looking at the pharmacokinetics of the drug can easily refute the argument of whether or not methadone is a long-acting opiate. Methadone has a very long serum half-life (24-36 hours, with atypical values up to 60-150 hours) 45. Serum half-life is not the same as duration of action. The onset of methadone action is from 30 minutes to 2 hours, and because of the long half-life of the serum, methadone can accumulate slowly in the patient’s tissue, which can falsely be interpreted as “prolonged duration of action” .
Methadone is not a long-acting or prolonged-release drug, which is reflected in its daily dose 3 to 4 times a day 45,57,58. However, because of their prolonged half-life, these unique properties allow methadone to be stopped abruptly without a significant risk of precipitating acute onset withdrawal. In addition, with methadone, if patients experience withdrawal symptoms, these symptoms usually appear 3 to 5 days later, not 2 to 3 days later, as with other opioids, reflecting the long half-life of the drug .59 Finally, the duration of analgesia is not (6-12 hours). This further demonstrates the need for multiple daily dosing and the potential to reach toxicity with frequent dose increases.59,60
Myth Number 9: Topical NSAIDs increase risk of cardiovascular disease and gastrointestinal bleeding
As noted, the FDA has taken two steps to increase awareness of the increased risk of CV and GI adverse events. These events can occur at any time during therapy and without prior notice. The risk of serious events is greater in elderly patients.61 These actions raise the question of whether these same warnings can be applied to topical NSAID formulations.2
To better answer this question, diclofenac NSAID, which exists in many dosage forms, can be used. A typical dose of diclofenac tablets is 50 mg orally 3 times daily. This dose generates a Cmax of 2270 ng / mL. The higher the Cmax of the drug, the greater the toxicity observed. In comparison, diclofenac gel generates a Cmax of 58.3, which is almost 40 times lower than that generated by the tablet.62 In addition, serum levels are so low and the percentage of diclofenac bound to albumin is so high that The level of drug available To cause toxic effects at any given time is minuscule.
To date, no case involving any non-salicylate NSAID topic leading to a toxic effect assigned to the NSAID class has been reported. Further research is needed to support the claim that even in small serum concentrations, patients exposed to chronic topical NSAIDs are at increased risk for CV disease.
Myth Number 10: NSAIDs lead to increased bone fusion time and decreased cure rate
This claim lacks conclusive evidence to support NSAID therapy that delays bone healing. Current literature on this subject only exists in animal models such as rabbits, dogs, goats, mice and rats. These results can not be extrapolated to humans, and in addition, the longest animal study was only 12 weeks. Fractures can take months to heal, so these animal studies do not provide conclusive evidence that short-term use of NSAIDs has any effect on long-term bone healing.
In addition, in 2008, Scott Ruben, MD, significantly advanced this argument and published more than 20 articles regarding positive results with the use of selective COX-2 NSAIDs in orthopedic surgery patients. However, it was revealed that this argument contained falsified data.63 These events also contributed to the negative association of NSAID use in the postoperative patient.
The review articles by Pountos et al, Vuolteenaho et al and Kurmis et al concluded that research on this subject is lacking and more data are needed to conclude whether NSAID therapy leads to an increase in time to bone fusion.64- 66
Much of the increased risk and many of the suspected adverse effects with these drugs can be addressed through appropriate monitoring or counseling by providers. In addition, providers who follow their patients closely can help dispel the myths surrounding these medications.