[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/) › Tramadol

[Pharmacology](https://durgical.com/en/pharmacology/) · [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

# Tramadol

A dual-action analgesic: a weak opioid and a serotonin and noradrenaline reuptake inhibitor. It can cause seizures and serotonin syndrome.

Updated 2026-11-01

- Class: [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)
- Receptor: μ-opioid receptor (mainly through the metabolite M1) and the serotonin and noradrenaline transporters
- ATC code: N02AX02

## ⚠ High-alert medication

An error with this medicine can cause serious harm: double checks and protocols are used.

◎**μ-opioid receptor (mainly through the metabolite M1) and the serotonin and noradrenaline transporters**Tramadol

ⓘ The figure shows morphine in the μ receptor; tramadol and its metabolite M1 occupy the same site. There is no structure of tramadol on a human target.

**Target in 3D:** μ-opioid receptor (mainly through the metabolite M1) and the serotonin and noradrenaline transporters. PDB structure 8EF6 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8EF6) · Drag to rotate · pinch to zoom

## Mechanism of action

Tramadol works in two ways. The parent drug is a weak μ agonist and inhibits serotonin and noradrenaline reuptake, which strengthens the descending pathways that inhibit pain. CYP2D6 turns it into O-desmethyltramadol (M1), a much more potent μ agonist. So ultra-rapid metabolisers risk poisoning, and serotonergic drugs add a risk of serotonin syndrome.

- Inhibits serotonin and noradrenaline reuptake in the spinal cord
- CYP2D6 turns it into M1, a more potent μ agonist
- The μ receptor and descending pain inhibition are activated
- Moderate pain relief; risk of seizures and serotonin syndrome

## Pharmacokinetics

**Absorption**
Well absorbed by mouth.

**Metabolism**
Liver: CYP2D6 to O-desmethyltramadol (M1, active) and CYP3A4 to other metabolites.

**Elimination**
Kidney; adjusted in severe kidney disease.

## Indications

- Pain severe enough to need an opioid when other options are not enough

## Adverse effects

### Common

- Dizziness and drowsiness
- Nausea and vomiting
- Constipation
- Headache and tiredness
- Abdominal pain

### Serious (rare, important)

- Life-threatening respiratory depression, above all at the start or after a dose increase
- Addiction, abuse and misuse, with risk of overdose and death
- Neonatal opioid withdrawal syndrome with prolonged use in pregnancy
- Adrenal insufficiency with prolonged use
- Severe hypotension
- Seizures, even at the recommended dose
- Serotonin syndrome
- Fatal respiratory depression in children who are ultra-rapid CYP2D6 metabolisers

## Contraindications

- Children younger than 12 years
- Postoperative management of tonsillectomy or adenoidectomy in under-18s
- Significant respiratory depression
- Acute or severe bronchial asthma without monitoring or resuscitation equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to the drug
- Use of monoamine oxidase inhibitors within the last 14 days

## Key interactions

**SSRIs, SNRIs, tricyclics, triptans and other serotonergic drugs**
Risk of serotonin syndrome; several of them also lower the seizure threshold.

**Benzodiazepines, alcohol and other central nervous system depressants**
Add up to profound sedation, respiratory depression, coma and death.

**CYP2D6 inhibitors (amiodarone, quinidine)**
More tramadol and less M1: shifts the balance between opioid and serotonergic effects.

**CYP3A4 inhibitors, or stopping inducers (rifampicin, carbamazepine, phenytoin)**
Raise tramadol levels, with a risk of seizures and serotonin syndrome.

**Monoamine oxidase inhibitors (current or within the last 14 days)**
Contraindicated: risk of serotonin syndrome or opioid toxicity.

## What is monitored

- Respiratory rate and sedation
- Signs of serotonin syndrome: agitation, tremor, fever, diarrhoea
- History of epilepsy or seizure risk factors

## Administration and safety

- All serotonergic drugs and drugs that lower the seizure threshold are reviewed before starting it.
- In overdose, naloxone reverses the opioid effect but may increase the risk of seizures.
- Controlled medicine: the order is verified, every dose recorded and leftovers kept secure.

## Nursing care

- Before each dose: respiratory rate, oxygen saturation and sedation level; hold the dose and report excessive sedation or slow breathing.
- Keep naloxone at hand and teach the family to recognise an overdose.
- Prevent constipation from the start and track bowel habits.
- Ask about a history of seizures and watch for them.
- Teach the symptoms of serotonin syndrome: agitation, sweating, tremor, fever, diarrhoea.

## Pregnancy and breastfeeding

Prolonged use in pregnancy can cause neonatal opioid withdrawal syndrome, which is expected and treatable; the newborn is watched after birth.

## Memory aid

TRAMADOL = a «TRAM with two DOors»: one opioid door, one antidepressant door. Two doors, two dangers: seizures and serotonin syndrome.

## Test yourself

Think of the answer, then tap the question to see it.

## What are tramadol's two analgesic mechanisms?

μ agonism (mainly through its metabolite M1, made by CYP2D6) and inhibition of serotonin and noradrenaline reuptake.

## Which two serious adverse effects set tramadol apart from other opioids?

Seizures, which can occur even at recommended doses, and serotonin syndrome, above all with SSRIs, SNRIs or other serotonergic drugs.

## What special caution applies to naloxone in a tramadol overdose?

It reverses the respiratory depression but may increase the risk of seizures.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/tramadol/)

## Related drugs

- [Codeine](https://durgical.com/en/pharmacology/codeine/)
- [Morphine](https://durgical.com/en/pharmacology/morphine/)

[← Back to the class: Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Tramadol: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a695011.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [TRAMADOL HYDROCHLORIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5852b90-e415-47ef-8f73-87266b58e033) (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 23 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N02AX02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/pharmacology/tramadol/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/tramadol/