Opioid analgesic central action of tramadol hydrochloride (tramal) in the treatment of chronic pain in cancer patients
Under opioid analgesics usually understand all natural and semi-synthetic derivatives of alkaloids as well as synthetic drugs that mimic the action of morphine. Synthetic opioids (agonists, mixed agonists – antigonists and antagonists) are classified as opioids. Tramal is a non-selective opioid receptor agonist. Highly effective analgesic effect is due to the content in it of the active substance tramadol hydrochloride. The drug is a strong opiate-like analgesic with a pronounced effect of inhibiting the perception of pain and the sensation of pain sensations. The analgesic effect can be more relieved by pre-administration of the nalorfine antagonist.
Tramal does not have any distinct antagonistic effects. According to researchers, the development of addiction and habituation of tramal should be attributed to a group of strong painkillers with very little potential for developing addiction. In therapeutic doses, practically does not cause respiratory depression and impairment of cardiovascular activity. The analgesic effect comes quickly and lasts for several hours. The drug has an antitussive effect, does not violate the motility of the gastrointestinal tract (GIT). The duration of the analgesic effect is 4-6 hours.
Absorption: most opioid analgesics are well absorbed from the subcutaneous and intramuscular injection sites, as well as from the nasal mucosa, oral cavity and gastrointestinal tract. However, although absorption through the mucous membrane of the gastrointestinal tract is fairly rapid, the bioavailability of some compounds when taken orally can be significantly reduced due to the pronounced effect of the first passage. Therefore, the dose while taking the drug inside should be increased compared with the dose for parenteral administration. Since the amount of enzyme responsible for this reaction is very variable in different people, the effective dose for taking the drug inside is difficult to predict. Tramal is rapidly and almost completely (90%) absorbed from the gastrointestinal tract.
The maximum plasma concentration is reached 2 hours after ingestion. Bioavailability with a single dose is 68% and increases with repeated use of the drug. After intramuscular injection, tramal is quickly and completely absorbed from the injection site. The concentration of the drug in the blood plasma is determined after 15 minutes.
Distribution: The supply of opioids to organs and tissues depends on a number of physiological and chemical factors. Although opioids bind to plasma proteins with different affinity, they quickly leave the blood and accumulate in tissues with high levels of perfusion, such as the lungs, liver, kidneys, and spleen.
Skeletal muscle fixes these drugs to a lesser extent, but it serves as the main reservoir of the substance because of its large mass.
Concentrations of opioids in the brain are usually low compared with other organs due to the presence of the blood-brain barrier. About 20% of trauma is bound to plasma proteins. Through the placental barrier the drug penetrates in a concentration equal to the concentration of the active substance in the plasma.
Metabbolism: A large part of the opioid is converted to polar metabolites, which are then rapidly excreted by the kidneys. Tramal is metabolized by de-methylation and conjugation of up to 11 metabolites, of which only one is active. Up to 90% of trauma is excreted by the kidneys, through the intestines – 10%. It is shown that bioavailability increases with age and the half-life of a tram increases due to age-related changes in liver function. However, these changes are minor, so a dose reduction is not required in older people with normal liver function.
In patients with impaired liver function, including cirrhosis, causing an increase in plasma tram concentration due to a decrease in hepatic clearance, a decrease in the dose and an increase in the interval between single dose doses have been shown.
In patients with impaired renal function, the elimination half-life of tram increases, which also requires an increase in the interval between single doses.
Compared to other analgesics, tramal, following the instructions set forth in the instructions for use, can be considered a relatively safe drug.