Tapentadol (brand name: Nucynta , Palexia and Tapal ) is a working opioid analgesic centrally from the benzenoid class with a dual mode of action as a -opioid receptor agonist and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4-6 hours.
This is similar to tramadol in a dual action mechanism; that is, its ability to activate your opioid receptor and inhibit norepinephrine reuptake. Unlike tramadol, it has only a weak effect on serotonin reuptake and is a significantly more potent opioid without known active metabolites. Tapentadol is not a pro-drug and therefore does not depend on metabolism to produce its therapeutic effect; this makes it a potent-moderate analgesic option useful for patients who do not adequately respond to more commonly used opioids because of genetic disposition (poor metabolism of CYP3A4 and CYP2D6), and provide more consistent dose-response ranges among patient populations..
The general potential of tapentadol exists somewhere between tramadol and morphine, with analgesic efficacy comparable to oxycodone although the incidence of adverse events is lower. It is generally regarded as a moderate-strength opioid (a category shared by many better known opioids such as hydrocodone and pethidine).
Tapentadol was approved by the US FDA in November 2008, by TGA Australia in December 2010 and by MHRA UK in February 2011.
Video Tapentadol
Medical use
Tapentadol is used for the treatment of moderate to severe pain for both acute (after injury, surgery, etc.) and chronic musculoskeletal pain. It is also specifically indicated for controlling the pain of diabetic neuropathy when an opioid drug is needed around the clock.
The general potential is somewhere between tramadol and morphine, with analgesic efficacy comparable to oxycodone despite the lower incidence of side effects.
Tapentadol is the Pregnancy Category C. There is no adequate and well-controlled tapentadol study in pregnant women, and tapentadol is not recommended for use in women during and immediately before delivery.
There is no adequate and well-controlled tapentadol study in children.
Maps Tapentadol
Contraindications
Tapentadol is contraindicated in people with epilepsy or who are prone to seizures. It increases intracranial pressure so it should not be used in people with head injury, brain tumors, or other conditions that increase intracranial pressure. This increases the risk of respiratory depression, so it should not be used in people with asthma. Like other mu-opioid agonists, tapentadol may cause sphincter of the Oddi sphincter, and is therefore not recommended for use in patients with bile duct disease such as acute and chronic pancreatitis. People who rapidly or very quickly perform metabolism for CYP2C9, CYP2C19, and CYP2D6 enzymes may not respond to tapentadol therapy. Due to permission reduction, tapentadol should be administered with caution to people with moderate liver disease and not at all in people with severe liver disease.
Adverse effects
The most frequently reported side effects of tapentadol therapy in clinical trials are nausea, vomiting, dizziness, drowsiness, itching, dry mouth, headache, and fatigue.
According to the World Health Organization there is little evidence to assess the potential abuse of tapentadol. Although preliminary pre-clinical trials show that tapentadol has a reduced responsibility for abuse than other opioid analgesics, the US DEA places tapentadol into Schedule II, the same category with stronger opioids more frequently used recreatively, such as morphine, oxycodone, and fentanyl.
Like the drug proto, O-desmethyltramadol, tapentadol has been shown to reduce the seizure threshold in patients. Tapentadol should be used with caution in patients with a history of seizures, and in patients who also take one or more other drugs that have also been shown to reduce the seizure threshold. High-risk patients include those who use other serotogenic and adrenergic drugs, as well as patients with head trauma, metabolic disorders, and those who use alcohol and/or drug withdrawal.
Tapentadol has been shown to potentially produce hypotension (low blood pressure), and should be used with caution in patients with low blood pressure, and patients taking one or more other drugs are also known to reduce blood pressure.
Interactions
Combination with SSRI/SNRI, CFS, serotonin receptor agonists can cause potentially lethal serotonin syndrome. Combination with MAOI can also cause adrenergic storms. The use of tapentadol with alcohol or other sedatives such as benzodiazepines, barbiturates, nonbenzodiazepines, phenothiazines, and other opiates can lead to increased decreases, sedation, respiratory depression, and death. Tapentadol is partially metabolized by the liver enzymes CYP2C9, CYP2C19, and CYP2D6 so that it innately has interactions with drugs that increase or suppress the activity/expression of one or more of these enzymes, as well as with the substrate of this enzyme (due to competition for the enzyme); some enzyme/substrate mediators require dose adjustment for one or both drugs.
The combination of tapentadol and alcohol may result in an increase in plasma tapentadol concentration and produce respiratory depression at a rate greater than the sum of both drugs when administered separately; patients should be cautious of alcohol consumption when using tapentadol because the combination can be fatal.
Tapentadol should be used with caution in patients who use one or more anticholinergic drugs, as this combination may cause urinary retention (which can lead to serious kidney damage and is considered a medical emergency).
Pharmacology
Tapentadol is a norepinephrine-receptor agonist and reeptake inhibitor (NRI). Analgesia occurs within 32 minutes after oral administration, and lasts for 4-6 hours. It is 18 times stronger than morphine in terms of binding to human human-enzyme receptors in in vitro studies of human tissue. In vivo, only 32% of the oral doses of tapentadol will survive past the first metabolism and proceed to the bloodstream to produce its effect on the patient's central and peripheral nervous system.
This is similar to tramadol in a dual action mechanism but unlike tramadol, it has many weaker effects on serotonin reuptake and is a significantly more potent opioid without known active metabolites.
Commercial preparations contain only stereoisomers (R, R), which are the weakest isomers in terms of opioid activity. The ratio of free base conversion to salt includes 0.86 for hydrochloride.
Peak plasma concentration (Cmax, the number of active drugs in the bloodstream) increased by 8% and 18% for IR tapentadol and ER preparation, respectively. This difference is not clinically significant, and tapentadol may be administered orally with or without food as circumstances allow, and patients will generally not notice a change in the effectiveness and/or duration of analgesic effects if the drug is not consistently administered in fasting or feeding conditions receive the same benefits from their doses regardless of what and when they last ate). The concentration of tapentadol plasma was different from the relevant level given the dose administered, with the highest tested dose (250 mg) yielding Cmax higher than expected through the dose-proportional plasma concentration. Increased doses of tapentadol should be anticipated to be slightly stronger than expected by the linear function of the previous dose-response relationship.
History
Tapentadol was discovered in the German pharmaceutical company GrÃÆ'¼nenthal in the late 1980s led by Helmut Buschmann; the team started by analyzing the chemistry and tramadol activity, which had been discovered in the same company in 1962. Tramadol has several enantiomers, and each forms a metabolite after it is processed in the liver. This tramadol variant has various activities in the -opioid receptors, norepinephrine transporters, and serotonin transporters, and different half-lives, with metabolites having the best activity. Using tramadol as a starting point, the team aims to find a molecule that minimizes serotonin activity, has a strong-opioid receptor agonist and strong norepinephrine reuptake inhibition, and will not require active metabolism; the result is tapentadol.
In 2003 GrÃÆ'¼nenthal partnered with two Johnson & amp; Subsidiaries Johnson, Johnson & amp; Johnson Pharmaceutical Research and Development and Ortho-McNeil Pharmaceutical to develop and market tapentadol; Johnson & amp; Johnson has exclusive rights to sell drugs in the US, Canada, and Japan while GrÃÆ'¼nenthal defends his rights elsewhere. In 2008 tapentadol received FDA approval; in 2009 was classified by DEA as drug of Schedule II, and entered the US market. Tapentadol is reported as the "first new molecular entity of an acting oral analgesic class" approved in the United States in more than 25 years.
In 2010 GrÃÆ'¼nenthal gave Johnson & amp; Johnson reserves the right to market tapentadol in approximately 80 additional countries. Later that year, tapentadol was approved in Europe. In 2011, Nucynta ER , a broad release formulation of tapentadol, was released in the United States for moderate to severe chronic pain management and received FDA approval the following year for the treatment of neuropathic pain associated with diabetes. peripheral neuropathy.
After annual sales of $ 166 million, in January 2015, Johnson & Johnson sold his right to market tapentadol in the US to Depomed for $ 1 billion.
Tapentadol is only marketed in countries where there is appropriate control. Since 2009 this drug has been categorized in the US as narcotics Schedule II with ACSCN 9780; in 2014 allocated an aggregate production quota of 17,500 kilograms. In 2010, Australia made tapentadol controlled drug S8. The following year, tapentadol was classified as controlled Class A drugs in the UK, and was also placed under national control in Cyprus, Estonia, Finland, Greece, Latvia and Spain. More recently, Canada has made controlled drug Schedule I opioids. After conducting a critical review, the United Nations Expert Committee on Drug Addiction suggested in 2014 that tapentadol was not placed under international control but remained under surveillance.
References
Source of the article : Wikipedia
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