• Biomolecules & Therapeutics
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• 제2권4호
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• pp.316-321
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• 1994

This study was undertaken to estimate whether nalbuphine, a mixed agonist/antagonist opioid analgesic produced psychic dependence. Moreover, the physical dependence liability of nalbuphine was compared with that of morphine after 7 days administrations of the drugs in mice and rats, and the effects of ginseng total saponin (GTS) on the development of physical dependence on nalbuphine were also studied. Nalbuphine did not produce psychic dependence. However, various abstinence signs precipitated by naloxone were observed in nalbuphine-dependent mice and rats. As the nature of the dependence syndrome produced by nalbuphine 30 mg/kg under these conditions seems similar to that induced by morphine 10 mg/kg, it is clear that nalbuphine possesses the substantial abuse potential. Therefore, nalbuphine may be needed to initiate more stringent controls for the prevention of nalbuphine abuse. On the other hand, GTS inhibited the development of physical dependence on nalbuphine and reduced the contents of dopamine and its metabolite in the brains of mice. Accordingly, results of this study suggest that the inhibitory effects of GTS on the development of physical dependence on nalbuphine may involve dopaminergic mechanism. GTS may be useful for the therapy of physical dependence on nalbuphine.

• 대한핵의학회지
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• 제27권1호
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• pp.22-27
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• 1993

Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of the drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of $^{99m}Tc$-HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction infused by zipeprol abuse.

• 대한임상독성학회지
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• 제7권2호
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• pp.172-175
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• 2009

Zipeprol dihydrochloride is a non-opioid mucolytic, antitussive agent and it is frequently prescribed for respiratory symptoms such as cough and sputum. The main pharmacologic mechanisms of zipeprol are inhibition of superior laryngeal nerve stimulation and direct antagonism for stimulation of the bronchial receptors, which might have an effect for the drug's mucolytic action. Many cases of drug abuse with zipeprol have occurred world-wide due to the hallucinogenic effect of the drug. In Korea, zipeprol was reported to be the most commonly abused drug among young people for the 1990s. Zipeprol associated death was first reported since 1991 and 69 cases of death related to zipeprol abuse were further reported during 8 years (between 1991 and 1998). In addition to the hallucinogenic effect, dyspnea, extrapyramidal symptoms, seizure, cerebral edema have been reported as the signs and symptoms of toxic zipeprol overdose. However, zipeprol abuse is not common for old age people and non drug abusers. We report here on a fatal case of acute zipeprol poisoning in an eighty five year old drug addicted woman.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.558-562
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• 2014

Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.

• Journal of Korean Neurosurgical Society
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• 제43권3호
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• pp.143-148
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• 2008

Objective: Postoperative delirium (POD) is characterized by an acute change in cognitive function and can result in longer hospital stays, higher morbidity rates, and more frequent discharges to long-term care facilities. In this study, we investigated the incidence and risk factors of POD in 224 patients older than 70 years of age, who had undergone a neurosurgical operation in the last two years. Methods: Data related to preoperative factors (male gender, >70 years, previous dementia or delirium, alcohol abuse, serum levels of sodium, potassium and glucose, and co-morbidities), perioperative factors (type of surgery and anesthesia, and duration of surgery) and postoperative data (length of stay in recovery room, severity of pain and use of opioid analgesics) were retrospectively collected and statistically analyzed. Results: POD appeared in 48 patients (21.4%) by postoperative day 3. When we excluded 26 patients with previous dementia or delirium, 17 spontaneously recovered by postoperative day 14, while 5 patients recovered by postoperative 2 months with medication, among 22 patients with newly developed POD. The univariate risk factors for POD included previously dementic or delirious patients, abnormal preoperative serum glucose level, pre-existent diabetes, the use of local anesthesia for the operation, longer operation time (>3.2 hr) or recovery room stay (>90 mini, and severe pain (VAS>6.8) requiring opioid treatment (p<0.05). Backward regression analysis revealed that previously dementic patients with diabetes, the operation being performed under local anesthesia, and severe postoperative pain treated with opioids were independent risk factors for POD. Conclusion: Our study shows that control of blood glucose levels and management of pain during local anesthesia and in the immediate postoperative period can reduce unexpected POD and help preventing unexpected medicolegal problems and economic burdens.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.45-51
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• 2011

These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

• 한국임상약학회지
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• 제33권1호
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• pp.22-34
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• 2023

Background: With the increasing use of narcotic analgesics, the Ministry of Food and Drug Safety has been operating the National Narcotics Information Management System (NIMS) since 2018 in Korea. Some studies are related to the narcotic analgesics use, but the evaluation studies of system, including NIMS users are insufficient. Objective: This study evaluated the NIMS enforcement process through in-depth interviews on the experience of using NIMS of doctors and pharmacists who prescribe or dispense opioid analgesics. Methods: Participants in this study were selected through purposeful sampling as three doctors and two pharmacists in the metropolitan area. The interviews were conducted from August 27 to October 19, 2022. Each interview was analyzed using a phenomenological method. Results: Six components of this study included "Doctors and pharmacists come across drug abusers", "They respond individually to drug abusers", "They use NIMS tailored to the needs of system managers", "They are concerned about the role of NIMS in practice settings", "They face challenges against drug abusers" and "They find a way to utilize the system to deal with drug abusers." The interviews confirmed that doctors and pharmacists used NIMS little in their work, and they only reported data. Therefore, it might be difficult for doctors and pharmacists to take measures for the safe use of narcotic analgesics. Conclusion: It is likely that adding data-feedback and medication-check function can reduce the abuse of narcotic analgesics. In the future, further studies on the evaluation of the empirical results of NIMS and review of systems in other countries will be required.