Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief begins within an hour, it is available by injection. It may be sold in combination as longer-acting formulations; as is typical of opioids, common side effects include constipation and nausea. Serious side effects may include seizures, increased risk of serotonin syndrome, decreased alertness, drug addiction. A change in dosage may be recommended in those with liver problems, it is not recommended in those who are pregnant. While not recommended in women who are breastfeeding, those who take a single dose should not stop breastfeeding. Tramadol acts by binding to μ-opioid receptors on neurons, it is a serotonin–norepinephrine reuptake inhibitor. It is converted in the liver to O-desmethyltramadol, an opioid with stronger binding to the μ-opioid receptor. Tramadol was patented in 1963 and launched under the name "Tramal" in 1977 by the West German pharmaceutical company Grünenthal GmbH.
In the mid-1990s, it was approved in the United States. It is available as a generic medication and marketed under many brand names worldwide. In the United States, the wholesale cost is less than US$0.05 per dose as of 2018. In 2016, it was the 39th most prescribed medication in the United States, with more than 19 million prescriptions. Tramadol is used to treat mild to severe pain, both acute and chronic, 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. On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine and is equally potent when compared with pethidine and codeine. For pain moderate in severity, its effectiveness is equivalent to that of morphine; these painkilling effects last about 6 h. Available dosage forms include liquids, drops, effervescent tablets and powders for mixing with water, tablets including extended-release formulations, compounding powder, injections.
As of 2015, tramadol was not approved in the United States for fibromyalgia. Based on three small trials with weak study design, fair evidence was found for tramadol as a second-line treatment. Use of tramadol is not advised for people deficient in CYP2D6 enzymes; the enzymes are crucial to the therapeutic effects of tramadol, by means of enabling tramadol's metabolism to desmetramadol. Tramadol's use in pregnancy is 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, its use during lactation is 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, its use as an analgesic during labour is not advised due to its long onset of action. The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labour pains has been estimated to be 1:94.
Its use in children is advised against, although it may be done under the supervision of a specialist. On September 21, 2015, the FDA started investigating the safety of tramadol in use in persons under the age of 17; the investigation was initiated because some of these people have experienced slowed or difficult breathing. The FDA lists age under 12 years old as a contraindication; the risk of opioid-related adverse effects such as respiratory depression, cognitive impairment and sedation is increased. The drug should be used with caution in those with liver or kidney failure, due to metabolism in the liver and elimination by the kidneys; the most common adverse effects of tramadol include nausea, dry mouth, abdominal pain, vomiting, constipation and headache. Compared to other opioids, respiratory depression and constipation are considered less of a problem with tramadol. Chronic opioid administration may induce a state of immune tolerance, although in contrast to typical opioids, it may enhance immune function.
Long-term use of high doses of tramadol causes withdrawal syndrome. These include both symptoms typical of opioid withdrawal and those associated with serotonin–norepinephrine reuptake inhibitor withdrawal. Psychiatric symptoms may include hallucinations, extreme anxiety, panic attacks, confusion. In most cases, tramadol withdrawal will set in 12 -- 20 hours after the last dose. Tramadol withdrawal lasts longer than that of other opioids. Seven days or more of acute withdrawal symptoms can occur as opposed to 3 or 4 days for other codeine analogues. A 2014 report by the World Health Organizations Expert Committee on Drug Dependence found:... in many cases of tramadol dependence, a history of substance abuse is present... but... the evidence for physical dependence was considered minimal. Tramadol is considered as a drug with low potential for dependence. In a recent German study, the low abuse and low dependence potential of Tramadol were re-confirmed; the German expert group found a low prevalence of abuse or de
Julian Bailey is a former professional rugby league footballer who played in the 1990s and 2000s. He played for Eastern Suburbs renamed the "Sydney City Roosters", from 1998 to 2000 and the Newcastle Knights from 2001 to 2002, he played for the Huddersfield Giants from 2003 to 2004. Bailey was born in New South Wales, he was a Hunter Mariners junior. Bailey began his first grade career with Eastern Suburbs to be renamed as the "Sydney City Roosters". Bailey played 3 seasons with the club but missed out on playing in the 2000 NRL grand final against Brisbane. In 2001, Bailey joined Newcastle and played 24 games for the club but was not included in the clubs premiership winning side who defeated Parramatta in the grand final. Bailey played on in 2002 with Newcastle and his last game for the club was the 38-12 semi final loss against his old club the Sydney Roosters. In 2003, Bailey joined English side Huddersfield and spent 2 years with them before retiring
Asheldham is a village and civil parish in Essex, England. It is located about 14 km southeast of Maldon and is 26 km east-southeast from the county town of Chelmsford; the village is in the district of Maldon and the parliamentary constituency of Maldon & East Chelmsford. The village is part of Dengie Parish Council, it is on the Dengie peninsula, is about 12 miles by road from Maldon. According to the 2001 census it had a population of 150, reducing to 142 at the Census 2011. A Ham class minesweeper launched in September 1953 was named after the hamlet. Media related to Asheldham at Wikimedia Commons Information and photographs of Asheldham village The history of Asheldham Asheldham in the Domesday Book