Tramadol: The Most Consumed Opioid

Tramadol is a centrally acting pain reliever. It belongs to the family of opioid drugs and acts on the central nervous system. However, its behavior is atypical compared to other opioids. It is also marketed as Adolonta, Gelotradol, Dolpar or Zytram, among other brands. The active substance is called tramadol hydrochloride and it is an analog of codeine.

It is often used in combination with acetaminophen to treat chronic pain. They are used in combination because they have been shown to be more effective together than alone. This is also due to the fact that the dose of both is reduced and, with it, the risk of side effects.

What is it for?

Tramadol is indicated for the treatment of moderate to severe pain in adults and adolescents from 12 years of age. The potency of tramadol is considered to be one tenth to one sixth that of morphine.

According to the world health organization -WHO-, tramadol is in rung II of the pain ladder. That is, on the moderate pain level. In it, weak opioids are classified as analgesics.

The absence of significant gastrointestinal and cardiovascular effects is a noteworthy fact. For this reason, tramadol is an  alternative for patients who do not tolerate non-steroidal anti-inflammatory analgesics -NSAIDs-.

Tramadol is also used in combination with acetaminophen for the treatment of chronic pain. It is a therapeutic option that improves patient comfort and adherence.

Opioid use data

The Spanish medicine agency -AEMPS- has published the report on opioid consumption in the period 2010-2017. These statistics show that opioid use has nearly doubled in recent years. The defined daily dose has gone from 9.9 to 17.7.

The most widely used group of opioids is opioids combined with other pain relievers. The most widely consumed active ingredient is the combination of tramadol and paracetamol (34.89%). And the second, tramadol alone (22.53%).

These data are undoubtedly a red flag. Opioid use should not be the first line of analgesic treatment. They are indicated only in moderate to severe pain that has not responded to other treatments.

The use of tramadol in chronic non-cancer pain in very high doses and for a long time is a questioned issue. Do not forget that it is an opiate that has addictive potential.

Mechanism of action of tramadol

Tramadol is composed of two enantiomers. Each of them acts by a different mechanism of action. And this is what makes it an atypical opioid:

• The (+) isomer exhibits preferential activity for the μ-opioid receptor.
• The (-) isomer  works by inhibiting the reuptake of norepinephrine and serotonin. Thus, it enhances the opioid analgesic effect of the (+) isomer.

Tramadol is a pure opioid receptor agonist. It is not selective, but has a higher affinity for μ-opioid receptors. The inhibition of the neuronal reuptake of norepinephrine and serotonin also contributes, on the other hand, to its analgesic effect.

Tramadol has an active metabolite: O-desmethyltramadol. Various studies show that the potency of this metabolite is several times greater than the original tramadol. Its analgesic activity is therefore critical for the analgesia of tramadol.

Side effects

The most common adverse reactions to tramadol treatment are nausea and dizziness. Other side effects that can also occur are:

• Headache
• Drowsiness.
• Fatigue.
• Hyperhidrosis -increased sweating-.

Due to its serotonergic effect, it is important not to combine it with other drugs that also act on serotonin. For example, some antidepressants such as SSRIs or amphetamine-type drugs.

It should also be noted that tramadol lowers the seizure threshold. Generally, it is not usually recommended in epileptic patients. Nor in combination with other drugs that lower this threshold in the same way.

Tramadol has a much lower potential than other opioids to induce respiratory depression. However, it is an adverse effect that can occur. In fact, it is an important point to consider when using tramadol as an anesthetic.

Especially in long-term treatment, tolerance and mental and physical dependence may develop. It should be taken into account and not used uncontrollably. In the case of discontinuation of treatment, it should be done gradually. Finally, it is important to bear in mind that the dose must be adjusted to the intensity of pain and the individual sensitivity of each patient. The lowest effective dose should always be used.