ent-dextilidine and Substance-Related-Disorders

Tilidine is an opioid analgesic that has been abused predominantly by the oral route. Studies of parenterally administered tilidine in animals did not clearly indicate a dependence potential of the morphine type. In this study we examined the abuse potential of orally and parenterally administered tilidine in humans. Both orally and intramuscularly given tilidine produced miosis and morphine-like subjective effects in non-dependent subjects. Oral tilidine was 1/8-1/10 as potent and intramuscular tilidine was 1/22 as potent as parenteral morphine in producing morphine-like subjective and miotic effects. Intramuscular tilidine suppressed and did not precipitate signs of abstinence in morphine-dependent subjects. However, intramuscularly given tilidine produced toxic effects not seen with morphine. Meperidine, codeine and d-propoxyphene produced morphine-like subjective and miotic effects, but also produced toxic effects at the highest doses tested. The results suggest that tilidine has a potential to be abused, that this potential is less than that of parenteral morphine and that tilidine is more likely to be abused orally than by the intramuscular route.

Topics: Administration, Oral; Adult; Codeine; Cyclohexanecarboxylic Acids; Dextropropoxyphene; Euphoria; Humans; Injections, Intramuscular; Injections, Subcutaneous; Male; Meperidine; Morphine; Substance-Related Disorders; Tilidine

Anesthesiologists have a well-known increased risk of substance abuse including the intravenous administration of opioids and propofol. However, katamnestic reports from the point of view of propofol-addicted anesthesiologists themselves are missing which would aid a better understanding of the dynamics and progress of addiction. This article presents an interview with a formerly addicted female anesthesiologist who after long-term abuse with oral tilidine combined with naloxone switched to intravenous administration of fentanyl and later on propofol. Several life-threatening incidents occurred but after some severe setbacks occupational rehabilitation outside the field of anesthesiology was successful following inpatient treatment. This case shows exemplarily in accordance with the current literature that warning signs in addicted physicians are often ignored by colleagues and supervisors and rehabilitation is possible under professional therapy and continuous surveillance. Additionally, this case emphasizes the necessity of controlling the distribution of propofol to reduce the life-threatening professional risk to anesthesiologists.

Topics: Adult; Analgesics, Opioid; Anesthesiology; Anesthetics, Intravenous; Female; Fentanyl; Humans; Naloxone; Opioid-Related Disorders; Physician Impairment; Physicians; Prescription Drug Diversion; Propofol; Substance Abuse, Intravenous; Substance-Related Disorders; Survivors; Tilidine

Non-medical abuse of prescription opioid medications is not a new phenomenon, but such use has been increasing in recent years. Various methods have been used and continue to be developed in an effort to limit diversion and abuse of opioid medications. A number of these methods will be described for opioid analgesic and addiction treatment formulations using relevant historical examples (e.g. propoxyphene, pentazocine, buprenorphine) as well as examples of formulations currently being considered or under development (e.g. oxycodone plus naltrexone, sustained-release buprenorphine). The focus, though not exclusively, will be on those formulations that represent a combination of an opioid agonist with an antagonist. These methods must take into consideration the pharmacokinetic profile of the agonist and antagonist, the expected primary route of abuse of the medication and the medication combination, the dose of medication that is likely to be abused, the availability of alternative drugs of abuse, and the population of potential abusers that is being targeted with the revised formulation.

Topics: Buprenorphine; Dextropropoxyphene; Drug Compounding; Drug Prescriptions; Humans; Narcotics; Pentazocine; Pharmaceutical Preparations; Substance-Related Disorders; Tilidine

Scheduled infusions of naloxone (1-100 micrograms/kg/inf.) and of buprenorphine (250 micrograms/kg/inf.) generated drug avoidance behavior in the non-dependent rhesus monkey under a continuous avoidance-escape paradigm. Pentazocine (1-100 micrograms/kg/inf.) codeine, (1-100 micrograms/kg/inf. and tilidine (1-250 micrograms/kg/inf.) were ineffective. Addition of varying doses of naloxone to scheduled infusions of codeine, tilidine, and pentazocine generated avoidance behavior not present with scheduled infusions of these opioids alone. The naloxone doses necessary for generation of avoidance behavior were low with the agonists codeine and tilidine, higher with the weak antagonist pentazocine, and highest with the strong antagonist buprenorphine. When monkeys were presented with the fixed tilidine-naloxone combination (100 + 8 parts) and pentazocine-naloxone combination (100 + 1 part) and the buprenorphine-naloxone combination (100 + 66 parts) presently in clinical use only the tilidine-naloxone combination generated drug avoidance behavior to an appreciable extent.

Topics: Animals; Behavior, Animal; Buprenorphine; Codeine; Drug Interactions; Female; Macaca mulatta; Male; Naloxone; Narcotics; Pentazocine; Reinforcement, Psychology; Substance-Related Disorders; Tilidine

Topics: Adult; Aged; Cyclohexanecarboxylic Acids; Female; Humans; Male; Middle Aged; Substance-Related Disorders; Tilidine

Topics: Adult; Cyclohexanecarboxylic Acids; Female; Germany, West; Humans; Illicit Drugs; Male; Substance Withdrawal Syndrome; Substance-Related Disorders; Tilidine

Tilidine (Valoron) is a new strong analgesic which was introduced into the market in West Germany in 1970. In February 1978 tilidine was placed under the regulations of the German Narcotics Act because it had rapidly become an easily acquired substitute for opiates on the drug scene. Cases have become known where tilidine dependence developed during the treatment of pain in patients without any preceding addiction to other drugs. The relevant literature on tilidine is reviewed in regard to pharmacological, epidemiological and clinical aspects of tilidine dependence and abuse.

Topics: Adult; Cyclohexanecarboxylic Acids; Drug and Narcotic Control; Germany, West; Humans; Iatrogenic Disease; Pain; Respiration; Substance-Related Disorders; Tilidine

Topics: Cyclohexanecarboxylic Acids; Delirium; Female; Humans; Male; Pain; Self Medication; Substance Withdrawal Syndrome; Substance-Related Disorders; Tilidine

Topics: Adult; Cyclohexanecarboxylic Acids; Hallucinations; Humans; Illicit Drugs; Sensation; Substance Withdrawal Syndrome; Substance-Related Disorders; Tilidine

Topics: Cyclohexanecarboxylic Acids; Humans; Male; Physician-Patient Relations; Substance-Related Disorders; Tilidine

Topics: Analgesics, Opioid; Anesthesia; Benzomorphans; Chemical Phenomena; Chemistry; Depression, Chemical; Humans; Morphinans; Naloxone; Narcotic Antagonists; Narcotics; Pentazocine; Respiration; Substance-Related Disorders; Tilidine

Contrary to previous clinical reports tilidin (Valoron), valuable as a strong analgesic, can replace opiates in young people addicted to them. In the drug scene, therefore, Valoron - very often through irresponsible medical prescription - has become a substitute for opiates. The results of an enquiry about Valoron abuse in 44 opiate addicts are reported. Four cases of isolated Valoron addiction are included which were indistinguishable from the typical career of an opium addict. Further cases of Valoron abuse, estimated at 600, have been mentioned to us, partly by name and partly by number. Doctors and pharmacists are urgently advised to treat Valoron with the same caution prescribed for opiates by the Betäubungsmittelgesetz (= Narcotics Act).

Topics: Adolescent; Adult; Cyclohexanecarboxylic Acids; Drug and Narcotic Control; Drug Utilization; Female; Germany, West; Humans; Male; Mental Processes; Opium; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Tilidine

Topics: Adult; Analgesics; Cyclohexanecarboxylic Acids; Humans; Male; Pain; Substance-Related Disorders; Tilidine