Tramadol

*Tramadol*

For medical students2 min readUpdated 2026-10-10

Tramadol is an analgesic with a mixed mechanism of action affecting the central nervous system. The drug combines opioid and non-opioid effects, providing effective pain relief for moderate to severe pain syndromes.

Mechanism of ActionOpioid receptor agonist and norepinephrine/serotonin reuptake inhibitor.

Dosage FormsCapsules, tablets, oral drops, injection ampoules, suppositories.

Routes of AdministrationOral, parenteral (IV, IM, SC), and rectal.

Safety ProfileLow abuse potential, minimal respiratory depression and gastrointestinal motility inhibition.

Mechanism of Action

The pharmacodynamics of Tramadol is unique and includes two components:

Opioid component: acts as a central non-selective agonist of $\mu$-, $\delta$-, and $\kappa$-opioid receptors.
Non-opioid (monoaminergic) component: inhibits the neuronal uptake of norepinephrine and serotonin, which enhances descending inhibitory pathways on pain impulse transmission in the spinal cord.

Pharmacological Effects

The drug exhibits pronounced analgesic activity, although it is less potent than morphine. A key advantage over classic opioids is its improved safety profile: Tramadol practically does not depress the respiratory center, does not reduce gastrointestinal motility (lower risk of constipation), and does not increase urinary tract tone.

Indications

Used for pain relief of various etiologies:

Postoperative pain.
Cancer pain.
Pain associated with myocardial infarction.
Traumatic injuries.

Administration and Dosage

The drug is available in a wide range of dosage forms: capsules (0.05 g), tablets (0.05 and 0.1 g), drops (0.1 g), 5% ampoules (1 and 2 ml), and suppositories (0.1 g).

Dosing Regimen:

Oral: 0.05–0.1 g (Maximal Daily Dose [MDD]: 0.4 g).
Parenteral (IV, IM, SC): 0.05–0.1 g (MDD: 0.4 g).
Rectal: 0.1 g (MDD: 0.4 g).

Mnemonic

Tramadol delivers a 'Double Hit': opioid receptor activation + monoamines (serotonin/norepinephrine reuptake inhibition).

Frequently asked questions

What effects does tramadol have on the central nervous system?

Tramadol exerts an analgesic effect on the central nervous system via a dual mechanism.

Opioid component — acts as a central non-selective agonist of $\mu$-, $\delta$-, and $\kappa$-receptors.
Non-opioid component — acts as a selective serotonin reuptake inhibitor and inhibits neuronal norepinephrine uptake, enhancing descending inhibitory influences on pain transmission in the spinal cord.

During overdose, the drug causes altered mental status, seizures, agitation, and respiratory depression, and can also trigger serotonin syndrome due to excessive serotonergic activity in the CNS.

What side effects does tramadol cause?

Tramadol causes several adverse reactions involving the gastrointestinal tract and the central nervous system. Key side effects include:

Frequent reactions — nausea, constipation, sleep disturbances, and dizziness.
Severe risks — venous thromboembolism, hip fractures, and increased mortality (compared to NSAIDs).
Specific complications — development of serotonin syndrome and the risk of dependence (drug addiction) with prolonged use.

What are the contraindications for tramadol use?

Sources indicate that tramadol is contraindicated in children under 14 years of age. For gonarthrosis, the drug is prescribed to patients aged 18 years and older.

Why is tramadol considered safer than morphine?

It has a significantly lower abuse potential, practically does not depress respiration, and does not cause severe constipation because it does not affect gastrointestinal motility as severely as classic opioids.

What is the non-opioid component of tramadol's action?

It blocks the reuptake of serotonin and norepinephrine, which enhances descending inhibitory pathways that suppress pain transmission in the spinal cord.

What is the maximal daily dose (MDD) of tramadol across different routes of administration?

Regardless of the route of administration (oral, parenteral, or rectal), the maximal daily dose is 0.4 g.

Go deeper

Comparative table of opioid analgesic activity.
Tramadol metabolism and the role of active metabolites.
Principles of combination pain therapy using non-narcotic analgesics.
Differences between full agonists and mixed-mechanism agonists.
Pharmacokinetic features of transdermal drug delivery systems.