The World Health Organization (WHO) Tiered Analgesia Scheme (1986) identifies combinations of different classes of medicines to relieve pain. These combinations are neopioid and opioid analgesics, adjuvants. Among the most commonly used products are plain analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), weak and potent opioids, tricyclic antidepressants and antiepileptic drugs. The combination of these formulations provides polymorphic pain relief, which helps to achieve greater analgesia, reducing the risk of high doses and side effects of one preparation. A combination of tramadol hydrochloride and dexketoprofen in one tablet is a new step in the polymorphic pain relief scheme, which provides hope for even better analgesia.
Since 1986 WHO Pain Relief Targets is the basis for pain management and guidelines for deciding on the concept of treatment with step-by-step administration in proportion to the patient’s reported pain level. Although the educational value and benefits of the WHO tiers, based on the prevalence of the method worldwide, are indisputable, the pain reliever tiers have certain disadvantages, especially when dealing with the different nature and aetiology of various pain-causing conditions.
Polymodial pain relief is the simultaneous use of pain relief medications that are assigned to different classes or with different mechanisms of action, which modulate different mechanisms and receptors, providing better pain control. This important concept is based on the theory that synergistic pain-relieving effects may be characteristic of co-administered agents with different mechanism of action. For optimal pain relief, the most effective dose for each substance is selected to ensure maximum efficacy and lower side effects . The potential benefits of a combination of dosage regimens for continuous pain relievers are more convenient dosage, a reduction in the number of tablets used, better compliance with the treatment regimen and, in the case of a steady-state combination of opiate and non-opioid drug combinations, more opioid use and a reduction in the incidence of side effects, lower dosage doses are used . One of the most recent polydrophilic pain tests is dexketoprofen and tramadol.
Dexketoprofen (DKP) is a ketoprofen S (+) enantiomer, which causes a typical effect of the primary NSAID, and the R (-) enantiomer does not show such an effect. The choice of a compound that is an active and well-known NSAID active ingredient has obvious potential benefits. First of all, it is possible to reduce the dose that is required to produce the same pain-relieving effect as with the initial racemic mixture. In addition, the burden of metabolism can be halved. The undesirable effects directly or indirectly induced by unnecessary isomers may also decrease. The pain-relieving effect of dexketoprofen is the same as the dose of twice as high as ketoprofen. Dexketoprophen is a very lipophilic drug and the tromethamine salt is highly soluble in water, resulting in rapid dissolution of the compound in the digestive system. Therefore, dexketoprofen tromethamol is more than 100 times more soluble in water than free form acid. It is rapidly absorbed in the upper gastrointestinal tract, reducing the effect of the substance in the entire intestinal tract, lower therapeutic doses and reducing undesirable side effects. Dexketoprofen trometamol is rapidly released into the systemic circulation, a higher amount of the drug gets into the CNS, and the compound acquires unique pharmacological properties.
Tramadol has a dual mechanism of action (a weak opiate antagonist and a weak inhibitor of noradrenaline and serotonin reabsorption) and is therefore an alternative to other opioid medicines, since these two complementary effects enhance the pain-relieving effect of the drug and improve tolerability. Unlike other opioids, tramadol does not have clinically significant cardiovascular and respiratory parameters and also has a small incidence of abusive and addictive development.
The results of preclinical studies confirm the antagonism of the interaction between NSAIDs and tramadol and suggest that the mechanism of this interaction is drug-induced serotonin excretion in the central nervous system and periphery. This idea is also supported by the antinociceptive effects detected in pre-clinical studies of dexketoprofen due to the activation of serotoninergic mechanisms.
The clinical efficacy of dexketoprofen and tramadol has been tested in classic surgical models: dental compression, bunionectomy, joint replacement surgery and soft tissue surgery. Dexketoprofen 25 mg / 75 mg tramadol 606 fixed dose combination in patients undergoing lower third molar removal reported moderate or severe pain, pain relief is constantly ensured; the effect started quickly, lasted for a long time, the undesirable effects were negligible. 25 mg dexketoprofen / 75 mg tramadol fixed-dose combination of 606 patients with through the abdominal wall has undergone hysterectomy caused pain killer effects, which was much stronger compared to the impact caused by separately used the same (25 mg dexketoprofen) or higher (100 mg tramadol) components to dose the following results: dexketoprofen 25 mg / 75 mg tramadol – 241.8 25 mg dexketoprofen – 184.5, 100 mg of tramadol – 157.3.