• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.343-349
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• 2018

Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of $GABA_A$ receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.

• Toxicological Research
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• v.17
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• pp.145-155
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• 2001

Cytochrome P4502C19 (CYP2C19) is one of human polymorphic xenobiotic-metabolizing enzymes. The enzyme has been reported to catalyze more than 70 substrates, involving more than 100 reactions. These include several classes of therapeutic agents (e.g. anti-microbial. cardiovascular, psycho-active, etc.), sex hormones and insecticides. Associations of the CYP2C19 genotype/phenotype with individual differences in drug efficacy (e.g. diazepam, omeprazole, proguanil) and toxicity (e.g. mephenytoin, barbiturates) have been documented by many investigators. At least 11 allelic variants of CYP2C19 gene were reported to date. Most of the mutant alleles found in the poor metabolizer (PM) led to the production of truncated and/or inactive proteins. Except for the exon 6, single-nucleotide mutations were reported in all nine exons of the gene. Genetic polymorphism of CYP2C19 shows marked interethnic variation with the population frequencies of PM phenotype ranging from 1∼2% up to more than 50%. The prevalence of CYP2C19 PM tends to be higher in Asian and certain Pacific Islanders than other race or ethnic specificity. Genotyping results of CYP2C19 also revealed that there are different proportions of individual mutant alleles among ethnic populations. This may, in part, explains the interethnic difference in the metabolism of certain drugs (i.e. diazepam), though they were from the same CYP2C19 phenotype. Recently, our research group has studied the genotype and phenotype of CYP2C19 and found that the PM frequency (7∼8%) in Thais is lower than other Asian populations. Molecular and clinical impacts of this finding warrant to further investigation.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.794-801
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• 2000

BOOP(Bronchiolitis Obliterans Organizing Pneumonia) is an inflammatory reaction that follows damage to the bronchiolar epithelium of the small conducting airways. BOOP is characterized by the pathologic finding of excessive proliferation of granulation tissue within the respiratory bronchioles, alveolar duct and spaces, accompanied by organizing pneumonia in the more distal parenchyma BOOP may result from diverse causes such as toxic fumes, connective tissue disorders, infections, organ transplantation and drugs or appear idiopathically. Drug induced BOOP has been described in association with acebutolol, amiodarone, cephalosporin, bleomycine, tryptophan, gold salts, barbiturates, sulfasalazine, and carbamazepine. Carbamazepine is an iminostilbene derivative that is used as both an anticonvulsant and pain reliever for pains associated with trigeminal neuralgia. It is structually related to the tricyclic antidepressants. To our knowledge, there have been no previously reported case that has described development of BOOP during carbamazepine treatment in Korea, and only two cases have been reported in the world. We report a case carbamazepine-induced BOOP with a brief review of literature.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.4
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• pp.823-829
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• 1997

The patients visiting pediatric dental office have been being younger than the previous, and they were often combined with systemic disease. But, we aren't able to perform the verbal communication, because of their impediment and youthfullness. And, we can't carry out the behavior control via physical restraint, as the developed social structure and the attitude of children and their parents. So, the importance and concerning of conscious sedation using sedative medicine are increased by time and time. Among the various conscious sedation, Chloral Hydrate and Nitrous Oxide inhalation are most popularly used, and barbiturates, benzodiazepine, opioids and hydroxyzine are used often. But, these medications have some side-effects and adverse reactions, may be failed to sedate the children. And limited use of medically compromised patients, especially for ASA class III, IV or more dangerous patients. We, the Department of Pediatric Dentistry, Chosun University have met some dangerous situation due to unfavorable pharmacogenic reactions, but we can control the situation and get well healed results. The below results are common situations and their solutions during conscious sedation. 1. By the intravenous administration, thrombophlebitis is the most common side-effects, but it may be healed with time without any special treatment. 2. Under the definitive guidelines about conscious-sedation, we can perform a safe conscious sedation for ASA class III patients. 3. When adversed reaction of Benzodiazepine is occured, it could be cared effectively with benzodiazepine antagonist, named Flumazenil.

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

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.88-95
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• 1986

Clinically, subhypnotic doses of barbiturates have been known to elicit hyperalgesia. In this experiment, effect of acute or chronic phenobarital treatment on the response to pain in rat was reevaluated by hot-plate method. To elucidate its mechanism, changes of ${\beta}-endorphin$ contents and [3H]-morphine binding of the rat midbrain as well as functional opiate receptor in vas deferens were also measured. Intraperitoneal injection of sub anesthetic dose phenobarbital induced initial hyperalgesia followed by successive analgesia, while chronic phenobarbital-treatment decreased reactivity to pain. Naloxone (10mg/kg, i.p.) markedly shortened hot plate latency period, and significantly inhibited the analgesic action of phenobarbital. Single dose of phenobarbital did not affect ${\beta}-endorphin$ contents and [3H]-morphine binding in rat mid brain, but in the chronic phenobarbital-treated groups, ${\beta}-endorphin$ contents was increased, while Bmax of opiate receptor binding was decreased. Moreover, very significant correlations among responses to pain, changes of ${\beta}-endorphin$ contents and opiate receptor binding were observed. However, Kd values of opiate receptor bindings were not changed in all preparations. In the chronic phenobarbital-treated vas deferens preparations, ID50 of morphine was increased witb concomittant decrease of maximum effect. But $pA_2 $, value for naloxone was not changed. From these results, it is suggested that phenobarbital can produce analgesia due to changes of ${\beta}-endorphin$ contents as well as functional opiate receptors by receptor regulation.