CYP2D6 polymorphisms show large geographical and interethnic differences. Variations in CYP2D6 activity may impact upon a patient's pain level and may contribute to interindividual variations in the response to opioids. This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol. For example, it is shown that (1) CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol. Notably, even though many studies investigated a possible role of the CYP2D6 polymorphisms on pain sensitivity, pharmacokinetics and pharmacodynamics of these drugs, the results of analgesia and adverse effects are conflicting. More studies are required to demonstrate genetically determined unresponsiveness and risk of developing serious adverse events for patients with pain and these should involve larger numbers of patients in different population types.
Matched MeSH terms: Codeine/adverse effects; Codeine/pharmacokinetics; Codeine/therapeutic use
Apart from routine analysis of total morphine content required by the criminal justice system, quantification of other major components in illicit heroin has not been considered by the Malaysian enforcement laboratory. In order to quantify various other cutting agents in addition to alkaloids, a gas chromatographic (GC) method was developed to facilitate simultaneous quantification of eight target analytes commonly found in illicit heroin seized in Malaysia within a 12 min run time. The validation results demonstrated high selectivity with the use of an HP Ultra 2 capillary column. Different solvents were studied and methanol:chloroform (1:9) proved best for sample dissolution. The method was repeatable and reproducible. The study ranges covering 50-150% of the preferred concentrations of the eight analytes obtained r(2)>0.9997. Limits of detection up to 6μg/mL were also obtained and the method achieved 99-102% recovery. The capability of the method in heroin profiling was verified using samples from ten case samples.
Southeast Asian countries including Malaysia play a major role in global drug trade and abuse. Use of amphetamine-type stimulants has increased in the past decade in Malaysia. This study aimed to apply wastewater-based epidemiology for the first time in Kuala Lumpur, Malaysia, to estimate the consumption of common illicit drugs in urban population. Influent wastewater samples were collected from two wastewater treatment plants in Kuala Lumpur in the summer of 2017. Concentrations of twenty-four drug biomarkers were analyzed for estimating drug consumption. Fourteen drug residues were detected with concentrations of up to 1640 ng/L. Among the monitored illicit drugs, 3,4-methylenedioxy-methamphetamine (MDMA) or ecstasy had the highest estimated per capita consumptions. Consumption and dose of amphetamine-type stimulants (methamphetamine and MDMA) were both an order of magnitude higher than those of opioids (heroin and codeine, methadone and tramadol). Amphetamine-type stimulants were the most prevalent drugs, replacing opioids in the drug market. The prevalence trend measured by wastewater-based epidemiology data reflected the shift to amphetamine-type stimulants as reported by the Association of Southeast Asian Nations Narcotics Cooperation Center. Most of the undetected drug residues were new psychoactive substances (NPSs), suggesting a low prevalence of NPSs in the drug market.
Consumption of curry containing poppy seeds has raised an issue concerning the opiate content in the urine that might exceed the cut-off value (300ng/mL). The main objective of this study was to examine the morphine and codeine contents in the urine of the consumers after partaking poppy seed-enriched curry in. The volunteers were asked to partake: (a) a single meal and their urines were collected within 24h, or (b) Two meals a day for three consecutive days and their urines were collected within 72h. Two different dosages were also tested in this study: (a) low dosage: 1g/100ml curry (containing 138μg of morphine and 66μg of codeine) and (b) high dosage: 5g/100ml curry (containing 690μg of morphine and 330μg of codeine). The subjects were randomised into the groups using the method of stratified randomization with age and gender groups as covariates. A total of 6 subjects was allocated for each group and placebos were used as control. Results showed that all subjects who consumed low dosage of poppy seeds either in single meal or multiple meals experiment were found negative. However, 1 out of 6high dosage subjects was confirmed positive at a period of 3-6h after the consumption of curry in the single meal study. This outlier maybe due to the lack of water consumption after consuming the curry, thus the low volume of urine was collected and the opiate was concentrated in the urine. On the other hand, 5 out of 6high dosage subjects in the multiple meals experiment were found positive. Majority of these subjects were found positive on the second and third day of the experiment after the second curry meal was consumed. The outlier (negative) in this group might be due to the high consumption of water throughout the experiment and the subject's urine volumes and frequency of urine collection were much higher compared to other subjects. From the result of this study, it can be concluded that partaking high dosages of poppy seed in curry could give a positive response (>300ng/ml+uncertainty of measurement) in the urine, and the water consumption after partaking curry has significant influence for the opiate contents in the urine.
Purpose: To examine the trends of analgesic prescribing at public tertiary hospital outpatient settings and explore the patterns of their utilization in nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and opioid patients.
Patients and methods: This cross-sectional study was conducted from 2010 to 2016 using the prescription databases of two tertiary hospitals in Malaysia. Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib, ibuprofen, indomethacin, meloxicam, mefenamic acid, and naproxen), tramadol, and five other opioids (morphine, fentanyl, oxycodone, dihydrocodeine, and buprenorphine) were included in this study. Annual number of patients and prescriptions were measured in repeat cross-sectional estimates. Descriptive statistics and linear trend analysis were performed using Stata version 13.
Results: A total of 192,747 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were given for 97,227 patients (51.8% NSAIDs patients, 46.6% tramadol patients, and 1.7% opioid patients) from 2010 to 2016. Tramadol (37.9%, n=72,999) was the most frequently prescribed analgesic, followed by ketoprofen (17.5%, n=33,793), diclofenac (16.2%, n=31,180), celecoxib (12.2%, n=23,487), and other NSAIDs (<4.5%). All the analgesics were increased over time except meloxicam, indomethacin, and mefenamic acid. Opioids, primarily morphine (2.2%, n=4,021) and oxycodone (0.5%, n=1,049), were prescribed the least, but the rate of increase was the highest.
Conclusion: Tramadol was the most frequently prescribed analgesic in hospital outpatient settings in Malaysia. Opioids were prescribed the least, but noted the highest increase in utilization.
Data source: Prescription databases of two public tertiary hospitals in Malaysia
Study site: two public tertiary hospitals in Malaysia