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.
Humans ; Beijing ; Wastewater-Based Epidemiological Monitoring ; Sewage/analysis* ; Wastewater ; Ketamine/analysis* ; Codeine/analysis* ; Methadone/analysis* ; Water Pollutants, Chemical/analysis*

INTRODUCTION: Misuse of prescription medicines and the harms associated with such use are growing threats across the world. There is currently, however, limited data on the extent of prescription medicine misuse in Singapore and whether this is a current threat in the country. METHODS: An online survey, limited to 1,000 individuals (aged 21 years and over) who were residents in Singapore, was administered through a survey panel company in September 2015. The survey collected information on participant demographics, and their awareness, self-reported lifetime and past-year misuse of commonly available prescription medicines in Singapore as well as the use of a range of recreational drugs and novel psychoactive substances (NPS). RESULTS: Lifetime (6.7%) and past-year (4.8%) misuse of any prescription medicine was comparable to lifetime (6.0%) and past-year (3.0%) use of any recreational drugs/NPS. The top five prescription medicines for lifetime misuse were: diazepam (2.7%); codeine (2.3%); dhasedyl (promethazine, codeine and ephedrine; 1.6%); panadeine (paracetamol and codeine; 1.5%); and methylphenidate (1.2%). The top five drugs for past-year misuse were: diazepam (1.6%); codeine (0.9%); panadeine (0.7%); alprazolam (0.6%); baclofen (0.6%); and gabapentin (0.6%). CONCLUSION Misuse of prescription medicine in Singapore was common, with prevalence comparable to the use of recreational drugs/NPS. A common source for misused drugs was physicians. Further studies are required to determine whether this is more widespread in Singapore and establish the different forms of drug diversion, so that appropriate prevention strategies can be implemented.
Humans ; Illicit Drugs/adverse effects* ; Public Health ; Singapore/epidemiology* ; Substance-Related Disorders/drug therapy* ; Prescription Drugs/adverse effects* ; Codeine ; Diazepam ; Prescriptions

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.
Aged ; Anxiety ; Ataxia ; Codeine* ; Depressive Disorder ; Depressive Disorder, Major ; Female ; Humans ; Migraine Disorders ; Neurology ; Pharmacokinetics ; Prescription Drug Misuse ; Pupil ; Reflex ; Reflex, Abnormal ; Serotonin Syndrome* ; Serotonin* ; Tremor ; Venlafaxine Hydrochloride

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.
Antidepressive Agents, Tricyclic ; Atomoxetine Hydrochloride ; Clinical Laboratory Services ; Codeine ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2C9 ; Cytochrome P-450 CYP2D6 ; Expert Testimony ; Genetic Testing ; Humans ; Insurance ; Isoniazid ; Korea ; Pharmacogenetics ; Protein-Tyrosine Kinases ; Tamoxifen ; Warfarin

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.
Bronchopneumonia ; Child* ; Codeine* ; Cytochrome P-450 CYP2D6 ; Diagnosis ; Drug Utilization Review ; Humans ; Inappropriate Prescribing ; Inpatients ; Insurance, Health ; Korea* ; Outpatients ; Prescriptions ; Primary Health Care ; Respiratory Insufficiency ; Rhinitis, Vasomotor

OBJECTIVETo explore the effect of auricular point sticking before operation for postoperative complications of external excision and internal ligation on mixed hemorrhoid.

METHODSEighty 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.

RESULTSAfter 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).

CONCLUSIONAuricular 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.

Acetaminophen ; administration & dosage ; Acupuncture Points ; Acupuncture, Ear ; Adult ; Codeine ; administration & dosage ; analogs & derivatives ; Combined Modality Therapy ; Female ; Hemorrhoids ; surgery ; Humans ; Ligation ; Male ; Middle Aged ; Postoperative Complications ; drug therapy ; prevention & control ; therapy

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.
Anticonvulsants ; Chemoradiotherapy ; Codeine ; Dexamethasone ; Drug Hypersensitivity ; Glioblastoma ; Humans ; Omeprazole ; Prognosis ; Radiotherapy* ; Skin ; Stevens-Johnson Syndrome* ; Trimethoprim, Sulfamethoxazole Drug Combination

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.
Acetaminophen ; Adrenal Cortex Hormones ; Adult ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Antitussive Agents ; Ascorbic Acid ; Child ; Codeine ; Common Cold* ; Complementary Therapies ; Cough ; Drug Therapy* ; Expectorants ; Garlic ; Geranium ; Histamine Antagonists ; Honey ; Humans ; Larynx ; Nasal Decongestants ; Nonprescription Drugs ; Nose ; Pharynx ; Probiotics ; Respiratory System ; Respiratory Tract Infections ; Zinc

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.
Adult ; Alleles ; Anaphylaxis* ; Asthma ; Basophil Degranulation Test ; Basophils ; Codeine* ; Constipation ; Cough ; Cytochrome P-450 CYP2D6 ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Eating ; Euphoria ; Female ; Food Hypersensitivity ; Genotype ; Histamine ; Histamine Release ; Humans ; Nausea ; Respiratory Tract Infections ; Rhinitis ; Seafood ; Skin ; Sleep Stages ; Thorax ; Urticaria

OBJECTIVE: To compare morphine and codeine concentration in urines of heroin abusers and codeine users and to discuss the judgment index to distinguish between heroin abuser and codeine user. METHODS: The urines of heroin abusers and codeine users were collected at different time periods. After protein precipitation, the urine samples were conducted for the qualitative and quantitative analysis of morphine and codeine by UPLC-MS/MS. And the results were all statistically analyzed. RESULTS: Statistical analysis showed that morphine and codeine concentration in urines of heroin abusers and codeine users were both abnormal distributions. The probability of the heroin abuser would be more than 95% and less than 5% for the codeine user when the concentration of morphine in urine sample was more than 67 ng/mL. The probability of the codeine user would be more than 95% and less than 5% for the heroin abuser when the concentration of morphine in urine sample was less than 67 ng/mL. CONCLUSION The morphine concentration in urine could be used as a criterion to distinguish the heroin abuser from the codeine user, while the codeine concentration could not.
Administration, Oral ; Chromatography, High Pressure Liquid ; Codeine/urine* ; Forensic Toxicology/methods* ; Heroin Dependence/urine* ; Humans ; Morphine/urine* ; Solutions ; Substance Abuse Detection/methods* ; Tandem Mass Spectrometry/methods*