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Tramadol hydrochloride (Ultram, Tramal) is a centrally acting synthetic opioid analgesic used in treating severe pain. While its action is not like that of other opioids, Tramadol is a synthetic analog of the phenanthrene alkaloid codeine. Bottle of 30 tablets of 200 mg extended-release tramadol HCl (generic Ultram ER) marketed by Patriot. Tramadol has been regularly used in the form of an ingredient in multi-agent topical gels, creams, and solutions for nerve pain, rectal foam, concentrated retention enema, and a skin plaster (transdermal patch) quite similar to those used with lidocaine.
Tramadol has a characteristic and unpleasant taste which is mildly bitter but much less so than morphine and codeine. The most commonly reported adverse drug reactions are nausea, vomiting, sweating, itching and constipation. Tramadol is associated with the development of physical dependence and a severe withdrawal syndrome.[36] Tramadol causes typical opiate-like withdrawal symptoms as well as atypical withdrawal symptoms including seizures.
It is apparent in community practice that dependence to this agent may occur after as little as three months of use at the maximum dose—generally depicted at 400 mg per day.
Because of the possibility of convulsions at high doses for some users, recreational use can be very dangerous.[44] Tramadol can, however, via agonism of ? opioid receptors, produce effects similar to those of other opioids (codeine and other weak opioids), although not nearly as intense due to tramadol's much lower affinity for this receptor. Tramadol and O-desmethyltramadol may be quantitated in blood, plasma or serum to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. The analgesic action of tramadol has yet to be fully understood, but it is believed to work through modulation of serotonin and norepinephrine in addition to its mild agonism of the ?-opioid receptor. The serotonergic-modulating properties of tramadol give it the potential to interact with other serotonergic agents. The overall analgesic profile of tramadol supports intermediate pain, especially chronic states.
Tramadol's primary active metabolite, O-desmethyltramadol, is a considerably more potent ?-opioid receptor agonist than tramadol itself, and is so much more so that tramadol can partially be thought of as a prodrug to O-desmethyltramadol. The chemical synthesis of tramadol is described in the literature.[62] Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Sweden, as of May 2008, has chosen to classify tramadol as a controlled substance in the same way as codeine and dextropropoxyphene. Grunenthal GmbH, which still owns the patent on Tramadol, has cross-licensed the drug to pharmaceutical companies internationally.
Tramadol for animals is one of the most reliable and useful active principles available to veterinarians for treating animals in pain.
The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia. Tramadol is converted to O-desmethyltramadol, a significantly more potent ?-opioid agonist. Tramadol is also molecularly similar to venlafaxine (Effexor) and has similar SNRI effects, with antinociceptive effects also observed. The 2010 Physicians Desk Reference contains several warnings from the manufacturer, which were not present in prior years. Extended-release tramadol is commonly available in 100, 200, and 300 mg strengths to be taken once daily.


The most well known dosing unit is the 50 mg generic tablet made by several manufacturers. The atypical withdrawal symptoms are probably related to tramadol's effect on serotonin and norepinephrine re-uptake. Grunenthal has promoted it as an opioid with a lower risk of opioid dependence than that of traditional opioids, claiming little evidence of such dependence in clinical trials (which is true; Grunenthal never claimed it to be non-addictive). Most commercial opiate immunoassay screening tests do not cross-react significantly with tramadol or its major metabolites, so chromatographic techniques must be used to detect and quantitate these substances. The contribution of non-opioid activity is demonstrated by the fact that the analgesic effect of tramadol is not fully antagonised by the ?-opioid receptor antagonist naloxone.
It is slightly less effective for acute pain than hydrocodone, but more effective than codeine.
Both codeine and tramadol share the 3-methyl ether group, and both compounds are metabolized along the same hepatic pathway and mechanism to the stronger opioid, phenol agonist analogs.
Tapentadol is also an opioid, but unlike both tramadol and venlafaxine, tapentadol represents only one stereoisomer and is the weaker of the two, in terms of opioid effect. Of these, O-desmethyltramadol is the most significant since it has 200 times the ?-affinity of (+)-tramadol, and furthermore has an elimination half-life of nine hours, compared with six hours for tramadol itself. Tramadol comes in ampules in addition to the tablets, capsules, powder for reconstitution, and oral syrups and liquids; the fact that its characteristic taste is distasteful to dogs, but can be masked in food, makes for a means of administration. It has a dual mode of action: mu agonism and mono-amine reuptake inhibition, which produces mild anti-anxiety results. Classes typically are comprised of sixteen students, a lead teacher, and one or more assistant teachers. The warnings include more compelling language regarding the addictive potential of tramadol, the possibility of difficulty breathing while on the medication, a new list of more serious side effects, and a notice that tramadol is not to be used in place of opiate medications for addicts.
Patients prescribed tramadol for general pain relief with or without other agents have reported withdrawal symptoms including uncontrollable nervous tremors, muscle contracture, and 'thrashing' in bed (similar to restless leg syndrome) if weaning off the medication happens too quickly. Symptoms may include those of SSRI discontinuation syndrome, such as anxiety, depression, anguish, severe mood swings, aggressiveness, brain "zaps", electric-shock-like sensations throughout the body, paresthesias, sweating, palpitations, restless legs syndrome, sneezing, insomnia, tremors, and headache among others.
They offer the theory that, since the M1 metabolite is the principal agonist at ?-opioid receptors, the delayed agonist activity reduces abuse liability. It has a dosage ceiling similar to codeine, a risk of seizures when overdosed, and a relatively long half-life making its potential for misuse relatively low amongst intermediate strength analgesics.
As with codeine, in the 6% of the population that have increased CYP2D6 activity (increased metabolism), there is therefore an increased analgesic effect. But unlike codeine and dextropropoxyphene, a normal prescription can be used at this time.[73] In Mexico, combined with paracetamol and sold under the brand name Tramacet, it is widely available without a prescription.
No data that would lead to a definitive determination of the efficacy and safety of tramadol in reptiles or amphibians is available at this time, and, following the pattern of all other drugs, it appears that tramadol can be used to relieve pain in marsupials such as North American opossums, Short-Tailed Opossums, sugar gliders, wallabies, and kangaroos among others.
Tramadol is also not to be used in efforts to wean addict patients from opiate drugs, nor to be used to manage long-term opiate addiction. The solutions suitable for injection are used in patient-controlled analgesia pumps under some circumstances, either as the sole agent or along with another agent such as morphine. Anxiety, 'buzzing', 'electrical shock' and other sensations may also be present, similar to those noted in Effexor withdrawal.


In most cases, tramadol withdrawal will set in 12–20 hours after the last dose, but this can vary.
It is, however, scheduled in certain states.[42] Nevertheless, the prescribing information for Ultram warns that tramadol "may induce psychological and physical dependence of the morphine-type".
Brand name formulations include Ultram ER, and the original Ultram from Ortho-McNeil (cross-licensed from Grunenthal GmbH).
In most Asian countries such as the Philippines, it is sold as a capsule under the brand name Tramal, where it is mostly used to treat labor pains. This is an advantage because the use of some non-steroidal anti-inflammatory substances in these animals may be dangerous. All teachers are qualified and experienced professionals who truly enjoy working with young children.
This characteristic distinguishes tramadol from many other substances (including morphine) of the opioid drug class, which generally do not possess tramadol's degree of subtype selectivity. Respiratory depression, a common side-effect of most opioids, is not clinically significant in normal doses. Tramadol withdrawal lasts longer than that of other opioids; seven days or more of acute withdrawal symptoms can occur as opposed to typically three or four days for other codeine analogues. Also, both tramadol and venlafaxine incorporate a cyclohexyl moiety, attached directly to the aromatic, while tapentadol lacks this feature.
Phase II hepatic metabolism renders the metabolites water-soluble, which are excreted by the kidneys. In reality, the closest structural chemical entity to tapentadol in clinical use is the over-the-counter drug phenylephrine. Tramadol should not be co-administered with selegiline or any other psychoactive class of medication such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, or monoamine oxidase inhibitors. When combined with SSRIs, tricyclic antidepressants, or in patients with epilepsy, the seizure threshold is further decreased. Animals suffering from diseases in these systems should be monitored by a veterinarian, as it may be necessary to adjust the dose. Seizures caused by tramadol are most often tonic-clonic seizures, more commonly known in the past as grand mal seizures. Also when taken with SSRIs, there is an increased risk of serotonin toxicity, which can be fatal. Fewer than 1% of users have a presumed incident seizure claim after their first tramadol prescription. Risk of seizure claim increases two- to six-fold among users adjusted for selected comorbidities and concomitant drugs.
Risk of seizure is highest among those aged 25–54 years, those with more than four tramadol prescriptions, and those with a history of alcohol abuse, stroke, or head injury.[25] Dosages of warfarin may need to be reduced for anticoagulated patients to avoid bleeding complications.



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