Codeine plus acetaminophen improve sleep quality, daily activity level, and food intake in the early postoperative period after photorefractive keratectomy: a secondary analysis / Melhora da qualidade do sono e das atividades diárias pós PRK imediato utilizando codeína com paracetamol: análise secundária de um ensaio clínico randomizado, duplo-cego e placebo-controlado

ABSTRACT Purpose: To determine whether codeine plus acetaminophen after photorefractive keratectomy (PRK) have beneficial effects on sleep quality, activity levels, and food intake, beyond their effect of pain relief. Methods: We enrolled 40 patients (80 eyes) in this randomized, double-blind, paired-eye, placebo-controlled, add-on trial. Each eye was treated 2 weeks apart, and the patients were randomly allocated to receive either the placebo or the intervention (30 mg codeine and 500 mg acetaminophen) (4 times a day for 4 days). Outcomes were sleep quality, daily activity level, and food intake within 24-72 h post-photorefractive keratectomy, as measured by the McGill Pain Questionnaire. Results: Sleep quality and daily activity level were inversely associated with pain scores within the first 48 h post-photorefractive keratectomy. During the intervention, patients were significantly more likely to score their sleep quality as good at 24 h (relative risk=2.5; 95% confidence interval 1.48-4.21, p<0.001) and 48 h compared to during placebo (relative risk=1.37; 95% confidence interval: 1.03-1.84, p=0.023). The probability of reporting good daily activity level at 24 and 72 hours post-photorefractive keratectomy was three times higher when patients received the intervention compared to the placebo (relative risk=3.0; 95% confidence interval: 1.49-6.15, p=0.006 and relative risk=1.31; 95% confidence interval: 1.02-1.67, p=0.021, respectively). No difference was observed in food intake. Conclusion: The oral combination of codeine and acetaminophen significantly improves sleep quality and daily activity level within the first 24-72 h post-photorefractive keratectomy compared to a placebo.

RESUMO Objetivo: Determinar se codeína (30 mg) mais pa­racetamol (500 mg) após ceratectomia fotorrefrativa fornece efeitos benéficos sobre a qualidade do sono, níveis de atividade e ingestão de alimentos além de seu efeito analgésico. Métodos: Quarenta pacientes (80 olhos) foram incluídos neste estudo randomizado, duplo-cego, pareado, placebo-controlado, add-on. Cada olho foi tratado com 2 semanas de intervalo, sendo aleatoriamente alocado para placebo ou intervenção (4x/dia durante 4 dias). Os resultados incluíram a qualidade do sono, atividade diária e ingestão de alimentos dentro de 24-72 horas de pós-operatório, conforme medido pelo McGill Pain Questionnaire. Resultados: A qualidade do sono e os níveis de atividade foram inversamente associados aos escores de dor nas primeiras 48 horas após o ceratectomia fotorrefrativa. Durante a intervenção, os pacientes foram significativamente mais propensos a classificar seu sono como bom em 24 horas (risco relativo=2,5, intervalo de confiança de 95%: 1,48-4,21, p<0,001) e 48 horas comparado ao placebo (risco relativo=1,37, intervalo de confiança de 95%: 1,03-1,84, p=0,023). A probabilidade de relatar bons níveis de atividade em 24 e 72 horas após ceratectomia fotorrefrativa também foi significativamente maior durante a intervenção em comparação com placebo (risco relativo=3,0, intervalo de confiança de 95%: 1,49-6,15, p=0,006 e risco relativo=1,31, intervalo de confiança de 95%: 1,02 -1,67, p=0,021, respectivamente). Nenhuma diferença foi observada entre a intervenção e placebo em relação à alimentação oral. Conclusão: A combinação de codeína e paracetamol melhorou significativamente a qualidade do sono e atividades diárias nas primeiras 24-72 horas após o ceratectomia fotorrefrativa em comparação com placebo.

Study on the Improvement of Quality Standard for Keqing Capsules / 中国药房

OBJECTIVE：To optimi ze and improve the quality standard for Keqing capsules. METHODS ：According to general rule 0502 method stated in 2015 edition of Chinese Pharmacopeia （part Ⅳ），TLC method was used to identify Reineckia carnea and Morus alba in Keqing capsules [the developing solvents were dichloromethane-ethyl acetate-formic acid （10 ∶ 4 ∶ 0.2，V/V/V） and ethyl acetate-carbinol-ammonia （12 ∶ 2 ∶ 1，V/V/V），respectively]. The contents of morphine and codeine phosphate in Keqing capsules were determined by HPLC. The determination was performed on XBridge C 18 column with mobile phase consisted of acetonitrile-0.01 mol/L potassium dihydrogen phosphate aqueous solution （pH value adjusted to 2.7 with 5％ phosphoric acid solution）（5 ∶ 95，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and the column temperature was 35 ℃. The sample size was 10 µL. RESULTS ：In TLC of R. carnea and M. alba in samples ，same color spots were shown in the correspon ding positions of reference substance chromatogram without interference from negative control. The linear range of morphine and codeine phosphate were batches of Keqing capsules were 0.97-1.37，0.16-0.37 mg/g，respectively. CONCLUSIONS ：TLC identification method for R. carnea and M. alba ，as well as HPLC content determination method for morphine and codeine phosphate in Keqing capsules are established；the method is simple ，accurate and reliable with strong specificity ，which improves the quality standard of Keqing capsules.

Cloning and sequence analysis of codeine-O-demethylase gene from Papaver somniferum and Papaver rhoeas / 药学学报

Codeine-O-demethylase (CODM) is a key enzyme in the biosynthesis of codeine and morphine. In this study, CODM gene sequences were cloned from Papaver somniferum and Papaver rhoeas, and were compared with each other by sequence alignment and bioinformatics analysis. The results showed that there were three genotypes of CODM in Papaver somniferum and five genotypes of CODM in Papaver rhoeas. Bioinformatics analysis showed that all CODM proteins had no signal peptide sequence, and these proteins were predicted to be non-secretory proteins, belonging to the Pcbc supergene family. Although the amino acid sequences of CODM in poppies are the same, the expression levels of CODM in different poppy resources are significantly different. It is speculated that the variation of transcription level of CODM may be related to its non-coding region sequence, which lays a foundation for further research on the synthesis and regulation mechanism of alkaloids in poppies.

Efecto del cosedal para el alivio del dolor postoperatorio en la cirugía de hernia inguinal / Cosedal effect for the post surgery pain relief in inguinal hernia surgery

RESUMEN Introducción: la analgesia preventiva en el paciente propuesto para cirugía constituye una de las problemáticas a investigar por las ciencias médicas, específicamente por la anestesiología. Objetivo: valorar el efecto del cosedal para el alivio del dolor postoperatorio en la cirugía de hernia inguinal. Materiales y métodos: se realizó un estudio prospectivo, longitudinal en la Unidad Quirúrgica Central del Hospital "Faustino Pérez Hernández". En el mismo fueron incluidos 86 pacientes distribuidos en dos grupos de igual número integrantes. Los pacientes del Grupo I recibieron dipirona 1,2 gramos IM media hora antes de la cirugía, mientras que a los del grupo II se les administró cosedal (tableta 60 mg) VO. Todos fueron intervenidos quirúrgicamente con anestesia subaracnoidea. Se estudiaron las variables edad, género, ASA, tiempo quirúrgico, tiempo anestésico, evolución del dolor postoperatorio y necesidad de analgesia de rescate. Resultados: la intensidad del dolor postoperatorio fue 1,2 veces menor en los pacientes del Grupo II. La necesidad de analgesia de rescate fue 1,3 veces mayor en los pacientes del Grupo I. Conclusiones: los pacientes del Grupo II mostraron menor intensidad del dolor postoperatorio las primeras 6 horas de la cirugía, en ellos los requerimientos de analgesia de rescate fue inferior (AU).

ABSTRACT Introduction: preventive analgesia in patients pending to a surgery is one of the major issues to be researched by the medical sciences specifically by anesthesiology. Objective: to evaluate cosedal effect for the post-surgery pain relief in inguinal hernia surgery. Materials and methods: a prospective, longitudinal research was carried out in the Central Surgical Unit of the "Faustino Pérez Hernández" hospital. In this research 86 patients were included and distributed in two groups with the same number of members. Half an hour before the surgery, Group I patients were administered 1.2 g of intramuscular dipyrone; while Group II patients were administered oral cosedal (60 mg tablet). They all were operated with subarachnoid anesthesia. Aspects such as age, gender, ASA, surgery time, anesthetic time, post-surgery pain evolution and need of rescue analgesia need were analyzed. Results: in Group II patients the post-surgery pain intensity was 1.2 times less than in Group I patients. The need of rescue analgesia was 1.3 times greater in Group I patients. Conclusions: group II patients showed a lower post-surgery pain intensity in the first six hours after the surgery and they needed less rescue analgesia (AU).

Use of viminol in acute pain management after third molars extraction. Case report / Uso do viminol no controle da dor aguda pós-extração de terceiros molares. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Acute postoperative pain of the third molars requires not only the ability of the dental surgeon in removing them but also the correct pharmacological control of this incidental pain that will install after the effect of the anesthetic blockade has ceased. The objective of this study was to report a case of moderate pain after third molar removal procedure, where the adverse effects of the prescribed medication were determinant for the abandonment of pharmacological treatment and consequently the maintenance of the pain. CASE REPORT: A 22-year-old male patient, student, from the city of Curitiba, sought outpatient care for acute moderate-intensity pain after 48 hours of removal of the third molars. He was experiencing some adverse effects due to the prescription of the combination of oral codeine (30mg) and paracetamol (325mg) at every 6 hours. In view of this, we opted for the prescription of viminol hydroxybenzoate (70mg) orally, every 6 hours. CONCLUSION: The prescription of the viminol hydroxybenzoate analgesic resulted in complete, rapid and effective postoperative analgesia, with excellent tolerability.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor aguda pós-operatória de terceiros molares requer não somente habilidade do cirurgião-dentista em removê-los, mas também no correto controle farmacológico desse quadro álgico que se instalará após o efeito do bloqueio anestésico ter cessado. O objetivo deste estudo foi relatar um caso de dor moderada pós-procedimento de remoção de terceiros molares, em que os efeitos adversos do fármaco prescrito foram determinantes para o abandono do tratamento farmacológico e consequentemente da manutenção da dor. RELATO DO CASO: Paciente do sexo masculino, 22 anos, estudante, natural de Curitiba, procurou atendimento ambulatorial por queixa de dor aguda de moderada intensidade, após 48 horas da remoção dos terceiros molares. Apresentou efeitos adversos devido à prescrição da associação de codeína (30mg) e paracetamol (325mg) por via oral de 6/6 horas. Frente a isso, optou-se pela prescrição de hidroxibenzoato de viminol (70mg) por via oral de 6/6 horas. CONCLUSÃO: A prescrição do analgésico hidroxibenzoato de viminol resultou em completa, rápida e eficaz analgesia pós-operatória, com excelente tolerabilidade.

Improvement and Optimization of Quality Standard for Qiangli Pipa Distillate Formula / 中国药师

Objective: To improve the quality standard for Qiangli Pipa distillate formula. Methods: The chemical reactions for i-dentification in the old standard were deleted. TLC methods were established to identify Papaveris pericarpium, Eriobotryae folium and Platycodonis radix. The contents of morphine and codeine phosphate from Papaveris pericarpium were determined by HPLC. The chro-matographic conditions for morphine content determination were as follows: an Inertsil ODS-3 chromatographic column (250 mm × 4. 6 mm, 5 μ m ) was used, the mobile phase was acetonitrile-the mixture of 0. 01 mol·L-1sodium heptane sulfonate and 0. 02 mol ·L-1potassium dihydrogen phosphate with equal amount (10% phosphoric acid was used to adjust pH to 2. 8) ( 13: 87 ), the detec-tion wavelength was 220 nm ,the column temperature was 30 ℃, and the flow rate was 1. 0 ml·min-1. The chromatographic condi-tions for codeine phosphate content determination were as follows : an Inertsil ODS-3 chromatographic column (250 mm×4. 6 mm, 5 μ m ) was used, the mobile phase was acetonitrile-the mixture of 0. 01 mol·L-1sodium heptane sulfonate and 0. 02 mol·L-1s potas-sium dihydrogen phosphate with equal amount (10% phosphoric acid was used to adjust pH to 2. 8) ( 15: 85 ), the detection wave-length was 220 nm, the column temperature was 30 ℃, and the flow rate was 1. 0 ml·min-1. Results: TLC had obvious characteris-tics with clear and well-separated spots. Morphine showed a good linear relationship within the range of 3. 14-62. 8 μg·ml-1( r=1. 000 0) with the average recovery of 96. 69% (RSD=2. 41% , n=9). Codeine phosphate showed a good linear relationship within the range of 3. 52-87. 94 μg·ml-1(r=1. 000 0) with the average recovery of 95. 68% (RSD=2. 64% , n=9). Conclusion: The quality standard for Qiangli Pipa distillate formula is improved. The methods are easy-operated and accurate with good specificity, which are suitable for the quality control of Qiangli Pipa distillate formula.

Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial

Abstract Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. Objective: The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. Material and Methods: This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. Results: In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P<0.05). In the Tr/Ac group, the scores significantly decreased over time from time point 6 h (P<0.05). Comparing the pain at each time point, the groups were not significantly different (P>0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. Conclusion: This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

Determination of SPE-HPLC Codeine Hydrochloride in Qiangli Pipa Syrup / 药物评价研究

Objective To establish the determination method of Codeine phosphate in Qiangli Pipa Syrup by RP-HPLC.Methods Using XDB-C18 Eclipse column (250 mm × 4.6 mm,5 ìm),acetonitrile:0.035 mol/L sodium acetate solution (glacial acetic acid to adjust pH =3.5) (25:75) as mobile phase,the flow rate was 1.0 mL/min,the detection wavelength is 240 nm,the column temperature is 40.Results the linear range of codeine phosphate in 2.024-40.24 ìg/mL was goody =8.18 × 105x + 12.2 (r =0.999 2);the average recovery rate was 98.2％ and RSD was 1.0％ (n =6).Conclusion This method is simple,rapid,accurate,and reliable,with high sensitivity,and could be applied to determination of Qiangli Pipa Syrup codeine hydrochloride content and controlment of the drug quality.

Simultaneous Determination of Morphine and Codeine Phosphate in Compound Liquorice Tablets by HPLC-ESI-MSMS / 中国药师

Objective:To establish a method to determine the content of morphine and codeine phosphate in compound liquorice tablets. Methods:The analysis was performed by HPLC-ESI-MSMS. The acquisition was MRM ( multi-reaction monitor) , the column wasAgilentZorbaxEclipseSBC18(2.1mm×100mm,3.5 μm),themobilephasewasacetonitrileand15mmol·L-1ammoniumac-etate with gradient elution. Results:The precursor (m/z) of morphine and codeine was 286. 0 and 300. 0, respectively, and the quan-titative ion was 165. 0 and 165. 0, respectively. The linearity of morphine was excellent between 25 and 500ng·ml-1 , and the average recovery was 103. 1%. The linearity of codeine was good between 0. 75 ng and 150 ng·ml-1 , and the average recovery was 101. 5%with RSD of 1. 7(n=6). Conclusion:The method is simple and accurate, which can be used for the quality control of compound ligu-orice tablets.

Brain Micro-structural Alterations of Cough Syrup Abuse Addiction Patients Containing Codeine Under Resting State / 中山大学学报(医学科学版)

[Objective]To investigate the micro-structural alterations within whole brain white matter(WM) in cough syrup abuse addiction patients containing codeine,and to explore the correlation between aberrant WH and abuse time of cough medicine abuse patients.[Methods]Thirty cough syrup abuse addiction patients containing codeine and 30 controls participated in the study. Structural changes in FA and(mean diffusivity)MD were examined in cough syrup abuse addiction patients containing codeine which derived from DTI tractography. Pearson correlation analysis was performed to compare the mean FA value and duration of cough syrup abuse addiction in patients.[Results]Cough syrup abuse addiction patients containing codeine had lower FA value in bilateral anterior limb of internal capsule(ALIC)and higher MD in the bilateral hippocampus and insula,right anterior cingulate cortex(ACC)and superior temporal gyrus,compared to the controls. Cough syrup abuse addiction group also had positive correlation between mean FAvalues and duration of cough syrup abuse addiction in patients.[Conclusion]Micro-structural alterations within whole brain white matter(WM)are found in cough syrup abuse addiction patients containing codeine. This disturbance progresses as duration increases of cough syrup abuse addiction in patients.

Simultaneous determination of four constituents in Kesuting Capsules by HPLC / 中成药

AIM To establish an HPLC method for the simultaneous content determination of four constituents in Kesuting Capsules (a fast cough suppressant,containing Ephedrae Herba,Papaveris Pericarpium,Platycodonis Radix,etc.).METHODS The analysis of trichloromethane-strong ammonia extract of Kesuting Capsules was performed on a 35 ℃ thermostatic Welch Ultimate(◎) XB-C18 column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.01 mol/L potassium dihydrogen phosphate buffer flowing at 1.0 mL/min in an isocratic elution manner,and the detection wavelength was set at 210 nm.RESULTS Morphine,ephedrine hydrochloride,pseudoephedrine hydrochloride and codeine phosphate showed good linear relationships within the ranges of 8.054-67.12 μg/mL (r =0.999 5),22.31-185.9 μg/mL (r =0.999 9),21.26-177.2 μg/mL (r =0.999 7) and 1.212-10.09 μg/mL (r =0.999 7),whose average recoveries (n =9) were 100.9％ (RSD =2.0％),101.4％ (RSD =3.6％),105.3％ (RSD =1.2％) and 106.2％ (RSD =1.2％),respectively.CONCLUSION This simple method can be used for the rapid quality control of Kesuting Capsules.

Codeine Precipitating Serotonin Syndrome in a Patient in Therapy with Antidepressant and Triptan

The serotonin syndrome is a serioius medical condition due due to an intensive stimulation of setonin receptors. It is a rare, but severe, consequence of interaction between serotomimetic agents. This is a report of a 70-year-old woman steadily in therapy with venlafaxine and rizatriptan for migraine and major depressive syndrome. She was admitted to neurology unit for decreased light reflex with miotic pupils, global hyperreflexia, tremor, anxiety, ataxia and incoordination. The patient was diagnosed as a probable case of serotonin syndrome due to a pharmacological interaction between venlafaxine and rizatriptan trigged by opioid intake. In this paper, the development of syntomatology, the clinical examination and the possible pharmacokinetics explanation were carefully discussed and analysed.

Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery / Comparação dos efeitos analgésicos pós-operatórios de naproxeno sódico e naproxeno sódico-fosfato de codeína em artroscopia de menisco

ABSTRACT BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18th hour on movement (p < 0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p < 0.001). Meperidine consumption was higher in Group N compared with Group NC (p < 0.001). There was no difference between groups with respect to side effects (p > 0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os anti-inflamatórios não esteroides (AINEs) são frequentemente usados para controlar a dor após artroscopia. A adição de um opiáceo oral eficaz (codeína) aos AINEs pode ser mais efetiva e diminuir o consumo de opiáceo parenteral no pós-operatório. O objetivo deste estudo foi comparar a eficácia e os efeitos colaterais de naproxeno sódico e uma nova preparação, naproxeno sódico-fosfato de codeína, quando administrados preventivamente para meniscectomia artroscópica. MÉTODOS: Foram randomicamente divididos em dois grupos 61 pacientes para receber naproxeno sódico por via oral (Grupo N) ou naproxeno sódico-fosfato de codeína (Grupo NC) antes da cirurgia. A cirurgia foi feita sob anestesia geral. Meperidina intravenosa foi iniciada por meio de analgesia controlada pelo paciente (ACP) para todos os pacientes. O desfecho primário foi o escore de dor na primeira hora de pós-operatório, avaliada com a escala visual snalógica (EVA). A sedação foi avaliada com a escala de sedação de Ramsey. A primeira demanda de ACP, o consumo de meperidina no pós-operatório, os efeitos colaterais e os dados hemodinâmicos também foram registrados. RESULTADOS: Os grupos foram demograficamente comparáveis. As medianas dos escores EVA tanto em repouso quanto em movimento foram significativamente menores no Grupo NC comparado com o Grupo N; exceto para movimento na avaliação de 18 horas (p < 0,05). A mediana do tempo até a primeira demanda de ACP foi menor no Grupo N em comparação com o Grupo NC (p < 0,001). O consumo de meperidina foi maior no Grupo N em comparação com o Grupo NC (p < 0,001). Não houve diferença entre os grupos em relação aos efeitos colaterais (p > 0,05). CONCLUSÕES: A combinação de naproxeno sódico-fosfato de codeína forneceu analgesia mais efetiva que naproxeno sódico, sem aumentar os efeitos colaterais.

Determination of Compound Codeine Phosphate Oral Preparations by Capillary Electrophoresis / 中国药师

To establish a method for the simultaneous determination of the active ingredients ( codeine phosphate, brompheniramine maleate, chlorpheniramine maleate, ephedrine hydrochloride and guaifenesin) in compound codeine phosphate oral preparations by capillary electrophoresis ( CE) . Methods:The method employed an uncoated capillary column ( eCAPTM ) from Beck-mann company (50 cm × 75 μm);the electrophoresis voltage was at 10 kV;20 mmol·L-1 phosphate buffer solution (pH 7. 5) was used;the UV measurement was at the wavelength of 214 nm. Results: The studied components had good linear ranges (r≥0. 995) within the range of the investigated concentrations. The recovery was no less than 96%. Conclusion:The presented method can be ap-plied in the content determination of active ingredients in compound codeine phosphate oral preparations from different enterprises. It is simple, efficient and universal, which facilitates the market supervision in a fast and valid manner.

Prescribing Patterns of Codeine among Children under Aged 12 in Korea

OBJECTIVE: Codeine may result in death or respiratory depression in children, particularly who are rapid metabolizer of CYP2D6, therefore it should be used cautiously among children under 12 years of age. This study was to investigate the prescribing pattern of codeine among children according to the age group, prescribed diagnosis, type of medical service and medical specialties. METHOD: We used Korea Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database. Study subjects included inpatients or outpatients, who were prescribed codeine between January, 1, 2011 and December, 31, 2011. Contraindicated use of codeine was defined as the use of codeine at least one times under aged 12. Age groups were sub-classified according to the <2 years, 2-4 years, 5-8 years, and 9-11 years. Frequently prescribed diagnosis (ICD-10), type of medical service, and medical specialties were also described among codeine users under aged 12. RESULTS: Codeine users were 6,411 inpatients (9,958 prescriptions), and 3,397 outpatients (6,258 prescriptions), respectively. Codeine prescription under 12 years of age were 2.1% (210 prescriptions) among inpatients, and 12.3% (776 prescriptions) among outpatients (p-value<0.05). Outpatient prescriptions of codeine under 12 aged were issued mostly from primary care clinics and frequent diagnosis were unspecified bronchopneumonia (51.6%), and vasomotor rhinitis (23.7%). CONCLUSION: This study found prescribing of codeine under 12 aged is common in outpatient and primary clinics. Nationwide and community-based efforts should be needed to reduce inappropriate prescribing among children.

A Case of Codeine Induced Anaphylaxis via Oral Route

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.

Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

Opioids are central analgesics that act on the CNS (central nervous system) and PNS (peripheral nervous system). We investigated the effects of codeine (COD) and tramadol (TRAM) on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA); local anesthetic without vasoconstrictor (LA WV); COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA) or TRAM 20 minutes prior to LA (TRAM 20' + LA). As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA). Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05). The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

Tosse: neurofisiologia, métodos de pesquisa, terapia farmacológica e fonoaudiológica / Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology

Introdução: A tosse é o sintoma respiratório mais comum em crianças e adultos. Objetivo: Apresentar uma revisão sobre a neurofisiologia e os métodos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiológica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos "tosse" ou "antitussígenos". Síntese dos dados: O reflexo da tosse envolve ativação de múltiplos receptores vagais nas vias aéreas e de projeções neurais do núcleo do trato solitário para outras estruturas do sistema nervoso central. Técnicas experimentais permitem estudar o reflexo da tosse ao nível celular e molecular para desenvolver novos agentes antitussígenos. Não há evidências de que antitussígenos isentos de prescrição médica tenham eficácia superior à do placebo para o alívio da tosse. A terapia fonoaudiológica pode beneficiar pacientes com tosse crônica refratária ao tratamento farmacológico, sobretudo quando coexiste movimento paradoxal das pregas vocais. Comentários Finais: A abordagem multidisciplinar tem papel fundamental no diagnóstico etiológico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antitussígenos de venda livre a fim de prevenir intoxicações e efeitos adversos, especialmente em crianças...

Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children...

Nonpigmenting Fixed Drug Eruption due to Codeine / 대한피부과학회지

Fixed drug eruption is a distinctive and clinically recognizable entity that is characterized by well-demarcated erythematous plaques recurring in exactly the same sites as on previous occasions. Unlike the pigmenting form of fixed drug eruption, nonpigmenting fixed drug eruption leaves no pigmentation when it resolves. We now report the case of a 44-year-old man who presented with diffuse ill-defined erythematous patches on both hands, feet and lower legs with a burning sensation, which is considered an atypical manifestation for fixed drug eruption. The patient had a history of similar skin lesions developing after medications on the corresponding regions. The patch test with suspected drugs showed negative reactions on both lesions and unaffected sites. The lesions were reproduced on the oral provocation test with codeine and resolved without pigmentation. The patient was diagnosed with nonpigmenting fixed drug eruption due to codeine.

Dopamine transporter SPECT imaging of the peroral addictors of compound codeine phosphate solution / 中华核医学杂志

Objective To study the damage to striatum in patients perorally addicted to compound codeine phosphate solution by using the brain dopamine transporter SPECT imaging. Methods Patients p erorally addicted to compound codeine phosphate solution ( n = 29 ) and addicted to heroin ( n = 27 ), as well as healthy volunteers (n = 31 ) were included in the study. Each of them underwent dopamine transporter (DAT) SPECT imaging with 99Tcm-2β-[N, N'-bis-( 2- mercaptoethyl ) ethylenediamino] methyl, 3β-(4-chlorophenyl)tropane (99Tcm-TRODAT-1). The striatum volume (V, cm3), mass (m, g) and radiactivity ratio (Ra) of striatum to whole brain were calculated using physio-mathematical modeling method.R esults Bilateral striatum of healthy volunteers showed typical "panda eyes" pattern and the distribution of DAT was uniform and symmetrical. Bilateral striatum of patients addicted to compound codeine phosphate showed impaired tracer uptake, similar to those addicted to heroin. The V, m and Ra of bilateral striatum of patients addicted to compound codeine phosphate were (23.68 ±4.94) cm3, (24.87 ±5.19) g and (5.01 ±0. 88 ) %, respectively, which were significantly lower than those of healthy controls: ( 35.39 ± 4.42 ) cm3,(37.16 ±4.64) g and (7.93 ±0.86)% (t = -9.69, -9.69, - 13.01, all P =0.000), but significantly higher than those addicted to heroin: ( 18.87 ± 4.66 ) cm3, ( 19.81 ± 4.90 ) g and (4.26 ± 1.02 ) % ( t =3.74, 3.74, 2.96, P = 0.000, 0.000, 0.005 ). Conclusion Long-term peroral intake of compound codeine phosphate solution may damage the function of cerebral striatum, which is someway similar to though less severe than, the impairment caused by heroin.