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Tramadol, sold under the brand name Ultram among others,[1] is an opioid pain medication used to treat moderate to moderately severe pain.[3] When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour.[3] It is also available by injection.[10] It may be sold in combination with paracetamol (acetaminophen) or as longer-acting formulations. Buying tramadol online

As is typical of opioids, common side effects include constipationitchiness, and nausea.[3] Serious side effects may include seizures, increased risk of serotonin syndrome, decreased alertness, and drug addiction.[3] A change in dosage may be recommended in those with kidney or liver problems.[3] It is not recommended in those who are at risk of suicide or in those who are pregnant.[3][10] While not recommended in women who are breastfeeding, those who take a single dose should not generally stop breastfeeding.[11] Tramadol is converted in the liver to O-desmethyltramadol (desmetramadol), an opioid with stronger binding to the μ-opioid receptor.[3][12] Tramadol is also a serotonin–norepinephrine reuptake inhibitor (SNRI).[3][13]

Tramadol was patented in 1963 and launched under the name “Tramal” in 1977 by the West German pharmaceutical company Grünenthal GmbH.[13][14] In the mid-1990s, it was approved in the United Kingdom and the United States.[13] It is available as a generic medication and marketed under many brand names worldwide.[3][1] In 2018, it was the 25th most commonly prescribed medication in the United States, with more than 24 million prescriptions

Medical uses

Tramadol (a schedule IV drug in the US) is used primarily to treat mild to severe pain, both acute and chronic.[17][18] There is moderate evidence for use as a second-line treatment for fibromyalgia but is not FDA approved for this use,[19] however, its use is approved for treatment of fibromyalgia as a secondary painkiller by the NHS.[20]

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Its analgesic effects take about one hour to come into effect and 2 to 4 h to peak after oral administration with an immediate-release formulation.[18][17] On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine (thus 100 mg is commensurate with 10 mg morphine but may vary) and is practically equally potent when compared with pethidine and codeine .[21] For pain moderate in severity, its effectiveness is equivalent to that of codeine at low doses, and hydrocodone at very high doses; for severe pain it is less effective than morphine.[17]

These painkilling effects last about 6 h.[18] The potency of analgesia varies considerably as it depends on an individual’s genetics. People with specific variants of CYP2D6 enzymes may not produce adequate amounts of the active metabolite (desmetramadol) for effective pain control.[9][17]

Sleep medicine physicians sometimes prescribe tramadol (or other opiate medications) for refractory restless legs syndrome (RLS);[22][23] that is, RLS that does not respond adequately to treatment with first-line medications such as dopamine agonists (like pramipexole) or alpha-2-delta (α2δ) ligands (gabapentinoids), often due to augmentation.[24]

Contraindications

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Tramadol may not provide adequate pain control for individuals with certain genetic variants of CYP2D6 enzymes as they metabolize tramadol to the inactive molecule.[17][9] These genetic polymorphisms are not currently routinely tested for in clinical practice.

Pregnancy and lactation

Tramadol’s use in pregnancy is generally avoided, as it may cause some reversible withdrawal effects in the newborn. A small prospective study in France found, while an increased risk of miscarriages existed, no major malformations were reported in the newborn.[26] Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. No evidence of this dose having a harmful effect on the newborn was seen.[26]

Labor and delivery

Its use as an analgesic during labor is not advised due to its long onset of action (1 hour).[26] The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labor pains has been estimated to be 1:94

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