Description

Simple

A medication used to treat moderate to severe pain.

Clinical

A centrally-acting opioid agonist and SNRI (serotonin/norepinephrine reuptake inhibitor) used for the management of moderate to severe pain in adults.

Overview

Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to [codeine] and [morphine]. Due to its good tolerability profile and multimodal mechanism of action, tramadol is generally considered a lower-risk opioid option for the treatment of moderate to severe pain. It is considered a Step 2 option on the World Health Organization's pain ladder and has about 1/10th of the potency of [morphine].

Tramadol differs from other traditional opioid medications in that it doesn't just act as a μ-opioid agonist, but also affects monoamines by modulating the effects of neurotransmitters involved in the modulation of pain such as serotonin and norepinpehrine which activate descending pain inhibitory pathways.[13] Tramadol's effects on serotonin and norepinephrine mimic the effects of other SNRI antidepressants such as [duloxetine] and [venlafaxine].

Tramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms and are also themselves metabolized into active metabolites: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agoni... Read more

Pharmacology

Indication

Tramadol is approved for the management of moderate to severe pain in adults.[29,30]

Tramadol is also used off-label in... Read more

Pharmacodynamic

Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.[ Read more

Mechanism of action

Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to [codeine] and [morphine]. Tramadol binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with 6000-fold less affinity than morphine.[ Read more

Absorption

**Oral Administration**

Tramadol is administered as a racemate, with both the [-] and [+] forms of both tramadol and the M1 metabolite detected in circulation. Following administration, racemic tramadol is rapidly and almost completely absorbed, with a bioavailability of 75%. This difference in a... Read more

Protein binding

About 20% of the administered dose is found to bind to plasma proteins. Protein binding appears to be independent of concentrations up to 10μg/mL. Saturation only occurs at concentrations outside of the clinical range.[ Read more

Volume of distribution

The volume of distribution of tramadol is reported to be in the range of 2.6-2.9 L/kg.[29,30] Tramadol has high tissue aff... Read more

Clearance

In clinical trials, the clearance rate of tramadol ranged from 3.73 ml/min/kg in renal impairment patients to 8.50 ml/min/kg in healthy adults.[29, Read more

Half life

Tramadol reported a half-life of 5-6 hours while the M1 metabolite presents a half-life of 8 hours.[ Read more

Route of elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are excreted primarily by the kidneys, accounting for 90% of the excretion while the remaining 10% is excreted through feces.[29, Read more

Toxicity

The reported LD50 for tramadol, when administered orally in mice, is 350 mg/kg.[ Read more

Adverse Effects

Contraindications

  • Regions: Canada
  • Excluded Age Groups:
    • pediatric
  • Below Age:
    • Amount: 12
    • Unit: year
  • Regions: Canada
  • Patient Conditions:
      • Name: Central nervous system depression
      • Drugbank Id: DBCOND0096632
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Head Injury
      • Drugbank Id: DBCOND0112466
  • Regions: Canada
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: Canada
  • Patient Conditions:
      • Name: Convulsive disorders
      • Drugbank Id: DBCOND0107830
  • Regions: Canada
  • Patient Conditions:
      • Name: Delirium Tremens (DTs)
      • Drugbank Id: DBCOND0107126
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute alcoholism
      • Drugbank Id: DBCOND0107892
      • Modification Of:
        • Base:
          • Name: Alcoholism
          • Drugbank Id: DBCOND0006017
        • Severity:
          • Includes:
            • acute
  • Regions: Canada
  • Patient Conditions:
      • Name: Cor Pulmonale
      • Drugbank Id: DBCOND0042897
  • Regions: Canada
  • Patient Conditions:
      • Name: Respiratory Depression
      • Drugbank Id: DBCOND0034868
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe COPD
      • Drugbank Id: DBCOND0050607
      • Modification Of:
        • Base:
          • Name: COPD
          • Drugbank Id: DBCOND0043004
        • Severity:
          • Includes:
            • severe
  • Regions: Canada
  • Patient Conditions:
      • Name: Status Asthmaticus
      • Drugbank Id: DBCOND0001831
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe bronchial asthma
      • Drugbank Id: DBCOND0107864
      • Modification Of:
        • Base:
          • Name: Bronchial Asthma
          • Drugbank Id: DBCOND0031527
        • Severity:
          • Includes:
            • severe
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe Hepatic Impairment
      • Drugbank Id: DBCOND0070791
      • Modification Of:
        • Base:
          • Name: Heptic Impairment
          • Drugbank Id: DBCOND0072269
        • Severity:
          • Includes:
            • severe
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe Renal Impairment
      • Drugbank Id: DBCOND0045819
      • Modification Of:
        • Base:
          • Name: Renal Impairment
          • Drugbank Id: DBCOND0031781
        • Severity:
          • Includes:
            • severe
  • Regions: Canada
  • Patient Conditions:
      • Name: Suspected surgical abdomen
      • Drugbank Id: DBCOND0107886
  • Regions: Canada
  • Patient Conditions:
      • Name: Ileus
      • Drugbank Id: DBCOND0010794
  • Regions: Canada
  • Patient Conditions:
      • Name: Bowel Obstruction
      • Drugbank Id: DBCOND0031840
  • Regions: US
  • Patient Conditions:
      • Name: Intoxication
      • Drugbank Id: DBCOND0022957
  • Hypersensitivity:
    • true
  • Regions: US

Food Interactions

  • Oral administration of tramadol hydrochloride with food does not significantly affect its rate or extent of absorption, therefore, tramadol hydrochloride can be administered without regard to food.

Interactions

Type in a drug name to check for interaction with Tramadol
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Tramadol can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1,10-Phenanthroline
The therapeutic efficacy of Tramadol can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine
2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Tramadol.
2,5-Dimethoxy-4-ethylthioamphetamine
2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Tramadol.
4-Bromo-2,5-dimethoxyamphetamine
4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Tramadol.
4-Methoxyamphetamine
4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Tramadol.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Tramadol is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Tramadol.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of serotonin syndrome and seizure can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Tramadol.
Abacavir
Tramadol may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Tramadol can be increased when combined with Abatacept.
Abediterol
The risk or severity of Tachycardia can be increased when Tramadol is combined with Abediterol.
Abemaciclib
The serum concentration of Tramadol can be increased when it is combined with Abemaciclib.
Abiraterone
The metabolism of Tramadol can be decreased when combined with Abiraterone.
Acarbose
Tramadol may decrease the excretion rate of Acarbose which could result in a higher serum level.
Acebutolol
The metabolism of Tramadol can be decreased when combined with Acebutolol.
Aceclofenac
Aceclofenac may decrease the excretion rate of Tramadol which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Tramadol which could result in a higher serum level.
Acepromazine
The risk or severity of hypotension and CNS depression can be increased when Acepromazine is combined with Tramadol.
Aceprometazine
The risk or severity of hypotension and CNS depression can be increased when Aceprometazine is combined with Tramadol.
30 References
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  27. 27 . FDA approvals Link
  28. 28 . WHO reports Link
  29. 29 . FDA Label - Tramadol File
  30. 30 . Health Canada Monograph - Tramadol File