About: Tilidine is a research topic. Over the lifetime, 90 publications have been published within this topic receiving 1249 citations. The topic is also known as: Tilidine racemate & ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate.
TL;DR: Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and oral bioavailability increased, and the disposition of a few opioids, such as fentanyl, sufent anil and remifentanil, appears to be unaffected in liver disease.
Abstract: The liver is the major site of biotransformation for most opioids. Thus, the disposition of these drugs may be affected in patients with liver insufficiency. The major metabolic pathway for most opioids is oxidation. The exceptions are morphine and buprenorphine, which primarily undergo glucuronidation, and remifentanil, which is cleared by ester hydrolysis. Oxidation of opioids is reduced in patients with hepatic cirrhosis, resulting in decreased drug clearance [for pethidine (meperidine), dextropropoxyphene, pentazocine, tramadol and alfentanil] and/or increased oral bioavailability caused by a reduced first-pass metabolism (for pethidine, dextropropoxyphene, pentazocine and dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, and clearance of morphine was found to be decreased and oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administration. Lower doses or longer administration intervals should be used to remedy this risk. Special risks are known for pethidine, with the potential for the accumulation of norpethidine, a metabolite that can cause seizures, and for dextropropoxyphene, for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine, respectively. If metabolism is decreased in patients with chronic liver disease, the analgesic action of these drugs may be compromised. Finally, the disposition of a few opioids, such as fentanyl, sufentanil and remifentanil, appears to be unaffected in liver disease.
TL;DR: A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care.
Abstract: A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented for quantitative determination of the opioids buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine in blood plasma after an automatically performed solid-phase extraction (SPE). Separation was achieved in 35 min on a Phenomenex C12 MAX-RP column (4 microm, 150 x 2 mm) using a gradient of ammonium formiate buffer (pH 3.5) and acetonitrile. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care.
TL;DR: The subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice, while considerable less information is available for the combination of tilidine and naloxone.
Abstract: . Background: Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. Methods: A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. Results: Analgesic efficiency...
TL;DR: Modern pharmacological pain management is based on non-opioid and opioid analgesics and adjuvant drugs, such as antidepressants or anticonvulsants, can be very effective especially in the treatment of certain types of pain.
Abstract: Persistent non-malignant pain is common, often neglected and under-treated among older persons. Some older adults do not complain because they consider chronic pain to be a characteristic of normal aging. Physicians have concerns regarding adverse effects of pharmacological treatment. The model of the World Health Organization for treatment of cancer pain is generally accepted and also recommended for persistent non-cancer pain. Furthermore, non-pharmacological treatment should complement drug treatment whenever possible. An initial assessment and possible treatment of underlying causes of pain are pertinent. Modern pharmacological pain management is based on non-opioid and opioid analgesics. NSAIDs are among the most widely prescribed class of drugs in the world. The new cyclo-oxygenase-2 inhibitors such as celecoxib and rofecoxib offer an alternative for the treatment of mild-to-moderate pain in patients with a history of gastric ulcers or bleeding. Paracetamol (acetaminophen) is being used widely for the management of mild pain across all age groups as it has moderate adverse effects at therapeutic dosages. For moderate pain, a combination of non-opioid analgesics and opioid analgesics with moderate pain relief properties (e.g. oxycodone, codeine, tramadol and tilidine/naloxone) is recommended. For severe pain, a combination of non-opioid analgesics and opioid analgesics with strong pain relief properties (e.g. morphine, codeine) is recommended. The least toxic means of achieving systemic pain relief should be used. For continuous pain, sustained-release analgesic preparations are recommended. Drugs should be given on a fixed time schedule, and possible adverse effects and interactions should be carefully monitored. Adjuvant drugs, such as antidepressants or anticonvulsants, can be very effective especially in the treatment of certain types of pain, such as in diabetic neuropathy. Effective pain management should result in decreased pain, increased function and improvement in mood and sleep.
TL;DR: These analgesic agents, like morphine, exert their effect at least in part through a spinal site of action as determined in the tail-flick test performed on rats.