• Archives of Pharmacal Research
• /
• v.6 no.1
• /
• pp.7-16
• /
• 1983

A methadone-diazepam interaction study in rats was performed in which conjugated metabolites of methadone were analyzed using deuterated biosynthetic internal standards. Diazepam (5mg/kg) was given to rats through a cannulate djugular vein and a subcutaneous dose of methadone (10mg/kg) was given. Bile was collecte through the cannulate dbile duct over a period of 24 hours. The deuterium label of the internal standards was found to be stable under conditions of the prolonged incubation. There was no significant difference in the excretion of the metabolites between the control and the diazepam treated rats. Feasibility of using biosynthetic internal standards with selected ion monitoring was established for the drug metabolism and kinetic studies.

• Toxicological Research
• /
• v.35 no.1
• /
• pp.9-12
• /
• 2019

One of the major challenges in methadone maintenance therapy (MMT) for drug dependence is the physiological side effects on endocrine hormones. Because of the key role of the thyroid gland in the normal functioning of the human body and brain, this study examined the effect of MMT on thyroid function. Thyroid hormones (T3, T4, and thyroid-stimulating hormone (TSH)) were evaluated in normal and user treated with MMT who were referred to the Province Clinical & Pathology Center of Urmia, Iran. The study was conducted for three months using the Case Series method. A total of 270 samples were collected, 215 were from individuals who were not treated, whereas 55 were from men treated with methadone. Average levels of T3 and T4 in non-treated sample of men are $1.34{\pm}0.02ng/mL$ and $90.96{\pm}1.38ng/mL$ while the corresponding values for patients treated with methadone are $1.39{\pm}0.04ng/mL$ for T3 and $94.57{\pm}2.72ng/mL$ for T4. Mean TSH levels of the non-treated group and the methadone consuming group were $1.75{\pm}0.08{\mu}IU/mL$ and $3.17{\pm}0.45{\mu}IU/mL$, respectively. These results indicate that although men treated with methadone had higher levels of T3, T4, and TSH than normal individuals, only the difference in TSH level was significant. The importance of this difference among individuals on methadone maintenance programs should be investigated in larger samples over long periods of time. Additionally, the effects of methadone treatment on women should be examined.

• Archives of Pharmacal Research
• /
• v.16 no.2
• /
• pp.83-88
• /
• 1993

opioid pure agonists, morphine, meperidine and methadone, were used to investigate the effect on the opioid receptor of fron sciatic nerve fibers using sucrose gap apparatus. When applied extracellularly by perfusion, morphine, methadone and meperidine significantly depressed the amplitude of the action potential in frog sciatic nerve fibers as a dose-dependent $(10^{-10}\;M-10^{-2}\;M)$ manner. The depression with morphine or methadone was partially antagonized by the simultaueous treatment with a lower $(10^{-10}\;M-10^{-8}\;M)$ concentration of naloxone, but that of meperidine was not blocked. When the three opioid agonists were applied intracellularly by placing it in a compartment with a cut end of the sciatic nerve fibers, all of themn depressed the amplitude of the action potentials by similar potency, and these reductions significantly blocked by pretreatment of lower concentration $(10^{-10}\;M-10^{-8}M)$ of naloxone. These results support the previous findings by other workers that the stereospecific opioid receptors of this preparation are located on or near the intracellular opening of the sodium channels which are sensitive to naloxone.

• The Korean Journal of Pain
• /
• v.35 no.4
• /
• pp.361-382
• /
• 2022

The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α₂ agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1992.05a
• /
• pp.40-40
• /
• 1992

opiate receptor들의 중추신경계에서의 분포 및 작용에 관한 실험물은 널리 알려져 있어 그 웅용 방법도 많이 있으나, 말초에 있는 opiate receptor의 존재 및 약물작용을 관찰하는 실험은 별로 알려진 것은 없다. 저자는 214mM의 sucrose 용역을 이용하여 전기적 자극에 따른 말초신경 및 말초조직(근육)에서의 opiate receptor애 대한 작용을 관찰하였다. 실험은 3분류의 약물을 이용하였다. 1) Pure agonists: morphine, meperidine, methadone, 2) Agonist-antagonist: buprenorphine 3) Pure antagonist: naloxone 위의 약물들을 이용하여 excitable cell membrane(좌골신경 및 근육)에서 일어나는 potential의 변화를 관찰하여 다음과 같은 결과를 얻었다. a. pure agonists들은 좌골신경 및 근육절편에서 action potentials을 의의있게 억제시켰으며 meperidine이 가장 강한 작용을 보였다. b. 이들의 작용은 naloxone 투여로 억제되었다. c. Agonist-antagonist인 buprenorphine은 투여용량 및 동시 투여한 pure agonist의 종류에 따라 biphasic pattern을 나타내었다. d. opiates 작용기전 및 약물작용장소를 알고자 두 종류, 즉 single 및 double technique을 사용하여 비교하였다.

• Journal of Yeungnam Medical Science
• /
• v.40 no.1
• /
• pp.78-85
• /
• 2023

Background: Poor sleep quality is associated with psychoactive substance abuse/addiction/withdrawal. Auricular acupuncture (AA) is a nonpharmacological method used for the treatment of sleep disturbances. This study aimed to examine the quality of sleep before and after AA in participants with mental and behavioral disorders due to prior multiple drug use in the therapeutic community. Methods: This was a consecutive case series of 27 participants (25 male [92.6%]). The median age was 35.0 years (interquartile range [IQR], 29.0-37.2 years), methadone/buprenorphine were not used, and the participants were treated with AA (median number of treatments, 15.0 [IQR, 12.0-18.0]) during a median period of 51.0 days (IQR, 49.0-51.0 days) according to the National Acupuncture Detoxification Association (NADA)-Acudetox protocol. Sleep quality was determined using the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month interval. Results: The global PSQI score dropped (indicating better sleep quality) by a median of 3.0 points (IQR, 0.0-8.0 points) after treatment. In the multivariate logistic regression analysis, with an increase in global PSQI score during AA by 1 point, there was a 0.73-fold reduction in the risk of poor sleep quality post-AA (adjusted odds ratio, 0.73; 95% confidence interval, 0.52-1.01; p<0.055; Nagelkerke's R² =0.66). Conclusion: The results revealed a positive effect of AA (by the NADA-Acudetox protocol) on sleep quality (as measured by PSQI) among participants in a treatment center with mental and behavioral disorders due to multiple drug use.

• YAKHAK HOEJI
• /
• v.52 no.2
• /
• pp.137-146
• /
• 2008

Even though driving under the influence of drug (DUID) is a worldwide problem, we, Korea has no regulation system yet except for alcohol, and there are little cases reported related to DUID. In order to investigate the type of abused drugs for drivers in Korea, we tried to analyze controlled and non-controlled drugs in alcohol-positive blood samples. 275 whole bloods, which were positive for alcohol on the roadside test, were collected from the police for two months ($Nov.{\sim}Dec.$ 2006). The analytical strategy was constituted of three steps: First, alcohol in blood samples were confirmed and quantified by gas chromatography. Second, controlled drugs were screened by $Evidence_{investigator}\;^{TM}$ (Randox, U.K.) as preliminary test. It was based on immunoassay by biochip array analyzer. Nine groups of drug abuse were screened: amphetamines, methamphetamines, cannabis, cocaine, opiates, barbiturates, methadone, benzodiazepines I (oxazepam) & II (lorazepam). Finally, confirmation of these drugs was performed by GC-MS. Blood samples were extracted by solid-phase extraction by $RapidTrace^{TM}$ (Zymark, U.S.A.). After trimethylsilyl (TMS) derivatization, eluates were analyzed to GC-MS. Total 49 drugs were investigated in this study including controlled drugs, antidepressants, 1st generation antihistamines, dextromethorphan, nalbuphine, ketamine, etc. For rapid detection, we developed the automated identification system. It was made up a new software, "DrugMan", modified Chemstation data analysis menu and newly developed macro modules. A series of peak selection, identification and reporting of the results were performed automatically by this system. Concentrations of alcohol in 275 blood samples were ranged from 0.011 to 0.249% (average, 0.119%). Among 149 blood samples, just six samples (4.0%) were showed positive results to the immunoassay: one methamphetamine and five benzodiazepines group I. By GC-MS confirmation, only benzodiazepines were detected and methamphetamine was not detected from immunoassay positive blood sample. Besides these drugs, 5 chlorpheniramines, dextromethorphan, diazepam, doxylamine, ibuprofen, lidocaine and topiramate were also detected in whole bloods by GC-MS. Conclusively, the frequency of drug abuse for Korean drivers was relatively low. There was none case which illegal drug was detected. However these results were limited to alcohol positive blood samples, so it is necessary to analyze more samples including alcohol negative blood.