Ultram is classified as a potent agent and we have is prescribed on a without prescription form for potent substances. Ultram is an opioid agonist, standing alone among all representatives of opioids of this class, primarily because, unlike them, it does not belong to narcotic drugs. This is confirmed by the extensive clinical experience of its use worldwide and special scientific studies of its narcotic potential.
The mechanism of analgesic action of Ultram is not completely identical to that of other opioid agonists. In contrast, Ultram has a dual mechanism of action. Due to the weak opioid and medium non-opioid effects, Ultram refers to analgesics of medium strength. The unusual dual mechanism of action of Ultram is explained by the fact that part of its molecules activates analgesic m-opioid receptors.
At the same time, the affinity of Ultram to these receptors is six thousand times weaker than that of morphine, so the narcogenic potential of this drug is minimal. The second part of Ultram molecules simultaneously activates non-opioid analgesic systems-inhibits the reuptake of serotonin or norepinephrine in nerve synapses. By activating the non-opioid noradrenergic and serotonergic systems, Ultram inhibits the transmission of pain impulses at the spinal level. The effect of each mechanism of action is quite weak, but in general, there is not just a summation, but multiple increases in the overall analgesic effect. It is the synergy of the two mechanisms of action of Ultram that determines its high efficiency. The low affinity of Ultram to opiate receptors explains the fact that in the recommended doses, Ultram does not cause respiratory and circulatory depression, impaired motility of the gastrointestinal tract (constipation), and urinary tract. Above all, it does not lead to the development of drug dependence with prolonged use.
Analgesic activity is 0.05-0.09 of morphine activity (according to some sources, this is 5 times lower than morphine, and 2 times higher than codeine activity); 50 mg of Ultram is equivalent to 1000 mg of Metamizole [21,19]. Thus, the scope of Tramal is a pain of moderate intensity.
The most important criterion for the safety of any opioid is the low severity of its central depressive effect on breathing and blood circulation. Numerous studies have not found significant respiratory depression in postoperative patients under the influence of Ultram in the therapeutic dose range from 0.5 to 2 mg per 1 kg of body weight, even with intravenous bolus administration, whereas morphine in the therapeutic dose of 0.14 mg/kg statistically significantly reduces the respiratory rate and increases the CO2 stress in the exhaled air. In the recommended doses, the drug does not cause respiratory depression, but it cannot be ruled out that it is possible when these doses are exceeded. Ultram has no depressing effect on blood circulation. In contrast, with intravenous administration of 0.75-1.5 mg/kg, it can increase systolic and diastolic blood pressure by 10-15 mm Hg. It is possible to increase the heart rate slightly with a rapid return to the initial values, which is explained by the sympathomimetic component of its action. There was no effect of the drug on the level of histamine in the blood and on mental functions [33].
Contraindications to the use of Ultram are:
- hypersensitivity to Ultram hydrochloride or opiates;
- simultaneous use of MAO inhibitors and a two-week period after their withdrawal;
- pregnancy and lactation (application is possible once only for life indications);
- drug withdrawal syndrome;
- children up to 14 years.
Experimental and clinical studies have shown that the ability to cause mental and physical dependence in Ultram is virtually absent. In the practice of European clinicians who use this drug since the late 70s of the XX century, the abuse of Ultram was very rare. Thus, for the first 14–year period of its use, the number of reports of abuse of Ultram (in terms of one million prescribed conditional doses) was 0.23, which is 40 and 30 times lower than when using dihydrocodeine and codeine phosphate in equivalent doses. In this regard, Ultram is not included in the convention on drugs under international control and is not subject to special accounting as a narcotic analgesic. All forms of the drug are included in the "List of potent drugs" and are written on the prescription form.