Estimation of the consumption level of four drugs in Beijing using wastewater-based epidemiology / 中华预防医学杂志

Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q1, Q3)] of 0.40 (0.22-0.8) ng·g-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q1, Q3)] of 0.13 (0.09, 0.17) ng·g-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q1, Q3)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant-1·day-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q1, Q3)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q1, Q3)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.

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.

A national study on the use of opioid analgesics in dentistry

Abstract The aim of this study was to assess the frequency of opioid analgesics prescribed by Brazilian dentists, potential regional differences and their association with socioeconomic and health-related factors. Data for all opioid prescriptions by dentists was obtained from the 2012 database of the National Controlled Substances Management System, regulated by the Brazilian Health Surveillance Agency. The number of defined daily doses (DDD) and DDDs per 1,000 inhabitants per day for each Brazilian state were calculated as the primary outcomes. DDDs were compared by regions and Brazilian states. Spearman's rho correlation coefficient was used to determine the influence of the states' characteristics, such as the Human Development Index; poverty; education; number of dentists per 100,000 inhabitants; visit to the dentist; dental care plan; good or very good oral health; number of pharmaceutical establishments per 100,000/inhabitants; and ability to get all prescribed medications. Data analysis was performed using IBM SPSS Statistics 25.0. A total of 141,161 prescriptions for opioids analgesics by 36,929 dentists were recorded, corresponding to 658,855 doses of opioids dispensed in 2012. The most commonly dispensed opioids were codeine associated with paracetamol (83.2%; n = 117,493). The national DDDs per 1,000 inhabitants per day was 0.0093 (range: 0.0002-0.0216). DDD per 1,000 inhabitants per day was positively associated to visits to dentists (rs = 0.630; P < 0.001) and inversely associated to poverty (rs = -0.624; p = 0.001). There are significant differences in opioid prescriptions in dentistry among the Brazilian states. These differences may be associated with non-clinical factors.

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).

A study of medical professionals' perspectives on medicines containing codeine in South Africa

Background: Misuse of codeine available on prescription and over-the-counter (OTC) has been highlighted as a potential problem in South Africa. Objective: To examine the perceptions of medical professionals regarding codeine use (prescribed and OTC), misuse, dependence and treatment options in South Africa. Method: Data for the study were obtained using a sample of medical professionals obtained through random and convenience sampling. A quantitative methodology was employed using a structured self-administered questionnaire with closed and open-ended items. Data analysis was conducted using SPSS version 21; 238 medical professionals involved in the prescribing of codeine completed the questionnaire. Results: Two-thirds of participants stated that they routinely reviewed patients prescribed codeine, and high levels of concern were expressed about the availability of OTC medicine containing codeine in pharmacies (84.9%) and on the internet (71.3%). There was agreement that medicines containing codeine should be regulated to a prescription-only medicine (85.3%). Only 22% of participants agreed that they had suitable screening methods to help with detection of codeine dependence. Eighty per cent indicated that they would welcome the opportunity for greater instruction on prescribing potentially addictive medicines. Conclusion: There appears to be a need to improve education on consumption and risks associated with codeine use. In addition, screening tools are needed to detect those with codeine dependence. Greater data sources are now needed to examine the sale of and consumption of codeine medicines in the interest of public health

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.

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.

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines Part 2

Pharmacogenetics is a rapidly evolving field and the number of pharmacogenetic tests for clinical use is steadily increasing. However, incorrect or inadequate implementation of pharmacogenetic tests in clinical practice may result in a rise in medical costs and adverse outcomes in patients. This document suggests guidelines for the clinical application, interpretation, and reporting of pharmacogenetic test results based on a literature review and the collection of evidence-based expert opinions. The clinical laboratory practice guidelines encompass the clinical pharmacogenetic tests covered by public medical insurance in Korea. Technical, ethical, and regulatory issues related to clinical pharmacogenetic tests have also been addressed. In particular, this document comprises the following pharmacogenetic tests: CYP2C9 and VKORC1 for warfarin, CYP2C19 for clopidogrel, CYP2D6 for tricyclic antidepressants, codeine, tamoxifen, and atomoxetine, NAT2 for isoniazid, UGT1A1 for irinotecan, TPMT for thiopurines, EGFR for tyrosine kinase inhibitors, ERBB2 (HER2) for erb-b2 receptor tyrosine kinase 2-targeted therapy, and KRAS for anti-epidermal growth factor receptor drugs. These guidelines would help improve the usefulness of pharmacogenetic tests in routine clinical settings.

Clinical observation of auricular point sticking combined with western medicine for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid / 中国针灸

<p><b>OBJECTIVE</b>To explore the effect of auricular point sticking before operation for postoperative complications of external excision and internal ligation on mixed hemorrhoid.</p><p><b>METHODS</b>Eighty patients with mixed hemorrhoid were randomly divided into an observation group and a control group, 40 cases in each group. In the control group, paracetamol and dihydrocodeine tartrate tablets were applied with oral administration 1 h after operation, 510 mg each time, twice a day; at the same time, diosmin tablets were treated with oral administration, 0.9 g each time, twice a day. Three days' treatments were required successively. In the observation group, auricular point sticking was used before operation based on the treatment in the control group. The auricular points of Shen (Co10), Pangguang (CO9), Shenmen (TF4), Pizhixia (AT4), Jiaogan (AH6a) and Gangmen (HX5) were selected. The patients were asked to press the points 3-6 times per day, 3-5 min each time, 3 days' treatment in total. The scores of the postoperative complications in the 1st and the 2nd days were compared between the two groups such as pain, edema, hematochezia, retention of urine, etc.</p><p><b>RESULTS</b>After operation, the scores of pain, edema, hematochezia, retention of urine in the 2nd day were all decreased obviously than those in the 1st day in the two groups (all P<0.05); and the scores of pain, edema, hematochezia, retention of urine in the 1st and the 2nd days of the observation group were lower than those in the control group (all P<0.05).</p><p><b>CONCLUSION</b>Auricular point sticking before operation combined with conventional western medicine with oral administration for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid achieves positive and reliable efficacy.</p>

Eficácia analgésica da associação de 30mg do fosfato de codeína com 500mg do paracetamol após exodontias de terceiros molares inferiores impactados / Analgesic efficacy of codeine phosphate 30mg association with paracetamol 500mg after extraction of impacted lower third molars

Avaliar a eficácia analgésica da associação de 30mg do fosfato de codeína com 500mg do paracetamol após exodontias de terceiros molares inferiores impactados. Foi realizado um estudo clínico bilateral com uma amostra de 47 pacientes. Em um dos lados, todos os pacientes receberam a dosagem de 30mg do fosfato de codeína em associação com 500mg do paracetamol após exodontia (grupo teste). Para a exodontia contralateral, foi disponibilizado outro frasco contendo cápsulas idênticas, porém com a dosagem de 500mg de paracetamol (grupo controle). 100% dos pacientes do grupo teste não necessitaram utilizar a medicação resgate e não consumiram doses adicionais da medicação após as cirurgias. No grupo controle, 44,7% dos participantes relataram o uso do medicamento resgate. O consumo total de comprimidos no grupo teste foi, em média, inferior quando comparados ao lado contralateral. 80,8% dos pacientes relataram maior conforto, quanto ao critério da dor, no lado em que foi utilizado a dosagem de 30mg de fosfato de codeína associado a 500mg de paracetamol. Os efeitos colaterais estiveram mais presentes no grupo teste, sendo mais comum o relato de sonolência (34%) e tontura (31,9%), não havendo relato de abandono desta medicação por nenhum dos pacientes. Concluímos que a dosagem de 30mg do fosfato de codeína associada a 500mg de paracetamol apresentou resultados favoráveis no controle da dor e uma baixa incidência de efeitos colaterais...

To assess the analgesic efficacy of regular dosage of codeine phosphate 30mg association with paracetamol 500mg after extraction of impacted lower third molars. We performed a bilateral clinical study analyzing a sample of 47 patients. All patients received a 30mg codeine phosphate dosage in combination with paracetamol 500mg after extraction (test group). For the contralateral tooth extraction, we had another bottle available containing identical capsules, with a 500mg paracetamol dosage (control group). 100% of the test group patients did not need to use rescue medication and did not consume additional doses of medication after surgeries. In the control group, 44.7% reported the use of rescue medication. Total consumption of pills in the test group was on average lower than the contralateral side. 80.8% of patients reported greater comfort, as the criterion of pain in the side that was used 30mg codeine phosphate dosage associated with paracetamol 500mg. The adverse effects were more present in the test group, with sleepiness being more common (34%) and dizziness (31.9%), without any patient medication abandonment. We conclude that the 30mg codeine phosphate dosage associated with paracetamol 500mg showed favorable results in controlling pain associated with a low incidence of side effects...

Drug therapy for the common cold

The common cold is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Drug therapies for the common cold are normally aimed at relieving the symptoms of the illness. Over-the-counter cough and cold medications should not be used in children younger than four years old because of potential harms and lack of benefit. Antibiotics, antitussives, anti-histamines, and inhaled corticosteroids are not effective in children. Products that may improve symptoms in children include expectorants, mucolytics, honey, vitamin C, zinc lozenges, geranium extract, and nasal saline irrigation. In adults, antihistamines, intranasal corticosteroids, codeine, intranasal ipratopium, and antibiotics are not effective. Decongestants, antihistamine/decongestant combi-nations, expectorants, and mucolytics may improve cold symptoms in adults. Nonsteroidal anti-inflammatory drugs and acetaminophen reduce pain secondary to upper respiratory tract infection in adults. Among complementary and alternative medicinetherapeutics, products containing vitamin C, zinc, or garlic may improve cold symptoms in adults. Prophylactic use of probiotics may decrease the frequency of colds in adults and children.

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.

Toxic Epidermal Necrolysis in Polymedicated Patient Treated With Radiotherapy

Temozolomide is an oral alkylating agent indicated for the treatment of patients with glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment. We report the case of a patient who developed toxic epidermal necrolysis (TEN) while she was being treated with chemoradiotherapy and several drugs. Cutaneous tests were performed with the drugs involved with negative result. Although the occurrence of TEN contraindicates suspected drug readministration, we based the decision to perform the controlled administration of temozolomide on the following reasons: (1) the poor prognosis of the underlying disease, (2) the lack of therapeutic alternatives, (3) the suspicion that other drugs taken by the patient simultaneously may be responsible (as anticonvulsants and trimethoprim sulfamethoxazole [TMP-SMX]), and (4) temozolomide was the first choice for treating the patient's disease. The administration of a cumulative dose of 60 mg of temozolomide caused a slight skin reaction. Given this result, we conducted controlled administration of other drugs involved. Dexamethasone, codeine, omeprazole and levetiracetam were well tolerated. However, TMP-SMX produced a similar reaction to that caused by temozolomide. In conclusion, we present the first case of TEN induced by temozolomide and TMP-SMX associated with cranial radiotherapy confirmed by controlled administration. Radiotherapy in combination with these drugs could have favored TEN, as some authors have postulated, but we cannot prove this.

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...