Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC–MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150 mg, caffeine 75 mg, and propyphenazone 375 mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5 ng/mg and 56.0 ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45 ng/mg and 11.1 ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC–MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective

Seizures of illicit substances for personal use in two Italian provinces: analysis of trends by type and purity from 2008 to 2017

Background: The use of illicit substances represents one of the most difficult problems to confront in the health system. Drug use is a global problem but is not uniform throughout the world, within the same country and changes over time. Therefore, knowing the illicit substances that are used in a territory is essential to better organize health services in that specific geographical area. To this aim, we analysed 4200 samples confiscated from individuals who held them for personal use by police forces in the Italian provinces of Modena and Reggio Emilia from 2008 to 2017. Methods: The suspected samples were screened by gas-chromatography-mass spectrometry (GC-MS) and by liquid chromatography-tandem mass spectrometry (LC-MS/MS); all samples were subsequently analysed by gas chromatography-flame ionization detector (GC-FID) for quantitative analyses. Results: Cannabis was the most seized illicit substance (70.7%). Over the study period, the number of seizures of herb with a high content of \u3949-THC increased. The number of cocaine seizures remained stable (total 16.1%), but the median purity of seized cocaine increased to 75% in 2017. Heroin seizures decreased over time, but the median purity of seized heroin reached 16.8% in 2017. In almost all the years, heroin samples with a purity exceeding the 97.5 percentile were found. Especially from 2014, the range of seized substances increased and started to include synthetic cathinones, phenylethylamines, UR-144, LSD, psilocybe, prescription opioid and hypnotics. In two cases, tramadol together with tropicamide was seized. Most of the seizures involved male subjects and 82% of the seizures were from individuals younger than 35 years of age. Conclusions: The persistence of old illicit drugs and the rapid emergence of new psychoactive substances represented a serious challenge for public health in the studied Italian area. Some useful interventions might be: informing mainly young people about the possible complications of cannabis use; implementing standardized procedures to diagnose and treat cocaine-related emergencies in hospitals; increasing the distribution of naloxone to antagonize possible heroin overdoses; equipping laboratories to be able to identify the new psychoactive substances

Monitoring of adherence to headache treatments by means of hair analysis

The aim of this study was to evaluate the potential of hair analysis to monitor medication adherence in headache patients undergoing chronic therapy. For this purpose, the following parameters were analyzed: the detection rate of 23 therapeutic drugs in headache patients' hair, the degree of agreement between the self-reported drug and the drug found in hair, and whether the levels found in hair reflected the drug intake reported by the patients

Hair analysis for detection of triptans occasionally used or overused by migraine patients-a pilot study

Purpose The aim of this study is to evaluate the detection rate of almotriptan, eletriptan, frovatriptan, sumatriptan, rizatriptan, and zolmitriptan in the hair of migraineurs taking these drugs; the degree of agreement between type of self-reported triptan and triptan found in hair; if the concentrations in hair were related to the reported cumulative doses of triptans; and whether hair analysis was able to distinguish occasional use from the overuse of these drugs. Methods Out of 300 headache patients consecutively enrolled, we included 147 migraine patients who reported to have taken at least one dose of one triptan in the previous 3 months; 51 % of the patients overused triptans. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed. Results All the triptans could be detected in the hair of the patients. The agreement between type of self-reported triptan and type of triptan found in hair was from fair to good for frovatriptan and zolmitriptan and excellent for almotriptan, eletriptan, sumatriptan, and rizatriptan (P < 0.01, Cohen’s kappa). The correlation between the reported quantities of triptan and hair concentrations was statistically significant for almotriptan, eletriptan, rizatriptan, and sumatriptan (P < 0.01, Spearman’ s rank correlation coefficient). The accuracy of hair analysis in distinguishing occasionally users from overusers was high for almotriptan (ROC AUC = 0.9092), eletriptan (ROC AUC = 0.8721), rizatriptan (ROC AUC = 0.9724), and sumatriptan (ROC AUC = 0.9583). Conclusions Hair analysis can be a valuable system to discriminate occasional use from triptan overuse

Un obiettivo primario della Tossicologia Forense: il raggiungimento della qualità - XIV Convegno Nazionale Gruppo Tossicologi Forensi Italiani -SIMLA

Gli autori presentano un caso di morte suicidiaria per asfissia da spazio confinato, in cui è stato rilevato il triazolam in concentrazioni sovrapponibili a quelle riferite dalla letteratura internazionale delle intossicazioni acute

Tramadol Abuse in a Binge Pattern in a Young Depressed Woman

Background: Tramadol is a central analgesic with a unique pharmacological profile in that it is an opioid agonist and an inhibitor of serotonin and norepinephrine reuptake. We describe a case of abuse of tramadol in a binge pattern in a young woman who had initially received the prescription of tramadol as an analgesic as needed. Case Description: The patient had no history of drug or alcohol abuse, but suffered from depression. Over time, she had increased the doses up to 30 ml of tramadol 100 mg/ml oral solution a week. She took the drug in consecutive ‘pinches’, from afternoon to evening. Tramadol improved her mood, gave her euphoria, but also caused constipation and urinary retention. Detoxi- fication was carried out by partial replacement with trama- dol 100 mg extended release and gradual reduction of the number of pinches. The patient found it hard to follow the program because of withdrawal symptoms of an opioid type and especially because of the worsening of depression. Conclusion: The action of tramadol on the monoaminergic sys- tem is believed to be a factor that limits abuse liability and gives advantageous antidepressant-like properties, but it also involves the risk of inducing abuse of the analgesic to improve mood as if it were a stimulant

Abuse of tramadol in a binge pattern in a young woman

Tramadol [(+)-trans-2-(dimethylaminomethyl)-l-(3-methoxyphenyl)-cyclohexanol HCl] is a central analgesic, widely used in the treatment of acute and chronic painful conditions of moderate and severe intensity. In comparison to opioid analgesics such as morphine, tramadol is considered to have a low potential to cause abuse and dependence (Raffa 2008). We described a case of abuse of tramadol in a binge pattern in a 32-year-old young woman who had initially received the prescription of tramadol as an analgesic as needed. She had no history of drug or alcohol abuse, but suffered from depression. Over time, despite having no more pain, she had increased the doses up to 30 ml of tramadol 100 mg/ml oral solution a week. She took the drug in consecutive "pinches", up to 48 (600 mg of tramadol) from afternoon to evening, until she fell asleep. Tramadol improved her mood, gave her euphoria and detachment, but also caused constipation and urinary retention. She reported intense fatigue, loss of appetite, insomnia, and tachycardia. Her physical health screen, neurological examination, lab tests, ECG, and a cardiology consult did not reveal any abnormalities. The total raw score of Zung Self-Rating Anxiety Scale was 49 and the Zung Self-Rating Depression Scale scored 68. Tramadol and M1 metabolite blood levels, determined by liquid chromatography/electrospray tandem mass spectrometry [LC/ESI-MS/MS (Agilent technology, Palo Alto, CA, USA)], were respectively 532 ng/ml and 318 ng/ml. Detoxification was carried out by a partial replacement with tramadol 100 mg extend release and a gradual reduction of the number of pinches. However, the patient found it hard to follow the program for the appearance of withdrawal symptoms of opioid type, and especially for the worsening of depression. After 40 days, when she was taking tramadol 150 mg/day, the patient left the treatment. A binge pattern of administration is typical of stimulant drugs such as cocaine and amphetamines, but it is unusual for an analgesic. However, tramadol has a unique pharmacological profile, as it is both a weak opioid agonist and an inhibitor of the reuptake of serotonin and norepinephrine. The expression of the opioid component is due primarily to the conversion in the M1 metabolite, also consisting of 2 enantiomers, that has a significant affinity for the opioid receptors. Instead, not metabolized tramadol has very low affinity for the opioid receptors and is an inhibitor of the reuptake of norepinephrine and serotonin (Gillen et al., 2000). It is likely that taking tramadol in a binge pattern the monoaminergic action could increase and the patient had obtained an intense effect of mood improvement, antidepressant-like. This hypothesis is supported by literature. In a study that characterized tramadol in a discrimination procedure in 8 subjects with active opioid and stimulant use, trained to discriminate among placebo, 8 mg hydromorphone, and 60 mg methylphenidate, an oral dose of tramadol 400 mg had stimulant-like effects and increased ratings on the stimulant scale (Duke et al., 2011). The action of tramadol on monoaminergic system is considered the basis of its antidepressant activity, observed in experimental animal models and reported as helpful in the treatment of pain patients. However, this antidepressant, stimulant-like effect also imply the risk of complicating the condition of the patients. Besides the opioid dependence, a strong link with the drug could indeed develop, maintained by the worsening of depression when trying to stop taking tramadol. In conclusion, tramadol can be abused to enhance mood in a binge pattern as if it were a stimulant agent. An extreme caution and a careful management of the therapy are therefore needed when tramadol is prescribed to patients with pain and depression

Monitoraggio dei pazienti con uso/abuso alcolico mediante la determinazione dell'Etil glucuronide (EtG) nel capello

Introduzione: L’Etil glucuronide (EtG) è un metabolita diretto di fase II dell’etanolo. E’rilevabile nel sangue per alcune ore, nell’urina per alcuni giorni e nella matrice cheratinica per diversi mesi. L’EtG-capello è emerso come biomarker utile a rilevare l’abuso di alcool e monitorare l’astinenza. Gli scopi di questo studio erano: 1. validare un metodo analitico per determinare la concentrazione dell’EtG nella matrice cheratinica, 2 applicare la metodica su casi clinici.Metodo: Hanno partecipato allo studio 98soggetti(66 Me 32 F, età media 49 anni), provenienti dal Day Hospital Alcologico del Policlinico e dal Centro Alcologico di Modena e seguiti per un periodo di 4 mesi. Sono stati raccolti 2 campioni di capelli, il primo giorno di ricovero (T0) e dopo 4 mesi (T1). La classificazione dei soggettiè stata effettuata mediante l’analisi dei questionari CIWA, Zung SDS-SAS ed SF-36 e dai colloqui individuali. Sono stati individuati 26 soggetti astinenti (14 M, 12 F) e 72 bevitori (52 M, 20 F) suddivisi rispettivamente in 16 “bevitori del week-end”(6 M, 10 F), 12 “social drinkers” (assunzione di alcool 60 g/die) (20 M, 4 F). La determinazione dell’EtG nel capello è stata effettuata mediante la tecnica analitica della cromatografia liquida elettrospray tandem spettrometria di massa (LC-MS-MS). La procedura estrattiva è stata eseguita mediante colonne Clean Screen® EtG Carbon (200 mg, 3 ml, UCT, USA). Tale tecnica è in grado di determinare concentrazioni di EtG dell’ordine di 4 pg/mg ed è idonea a discriminare le concentrazioni di EtG nei soggetti astinenti (30 pg/mg). I capelli di lunghezza >3 cm sono stati suddivisi in segmenti per verificare il consumo alcolico pregresso.Risultati:Solo 12 di 44 soggetti che assumevano quantità di alcool >40 g/diepresentavano una concentrazione di EtG 40 g/die e nei social drinkers vi era una scarsa correlazione tra quantità di etanolo dichiarata e la concentrazione di EtG misurata nei capelli. Nel secondo campione di 14 pazienti che si erano dichiarati assuntori continuativi di bevande alcoliche vi era una diminuzione della concentrazione di EtG nei capelli (ad eccezione di due soggetti), in linea con una diminuita assunzione di bevande alcoliche e una buona aderenza al trattamento. L’analisi segmentale dei capelli ha consentito di supportare o smentire le dichiarazioni dei soggetti e soprattutto di rafforzare l’ipotesi diagnostica.Conclusioni: I risultati ottenuti sostengono l’ipotesi che il valore di EtG >50 pg/mg possa individuare i soggetti appartenenti alle categorie “hazardous drinkers” e “heavy drinkers”, ovvero soggetti che assumono quantità >60 g/die. L’analisi segmentale del capello offre la possibilità di definire, contestualmente all’anamnesi, la storia di uso/abuso di sostanze alcoliche protratta nel tempo e caratterizzarne l’intensità attraverso l’analisi quantitativa

Mefedrone: una nuova designer drug identificata nel mercato clandestino

recentemente il mercato delle droghe ha subito un considerevole cambiamento: accanto alle sostanze d'abuso tradizionalmente segnalate si \ue8 delineato l'incremento delle 'designer drug', le droghe sintetiche, rappresentate da numerose sottoclassi. la finalit\ue0 del contribbuto \ue8 rivolta da un lato ala caratterizzazione chimico-tossicologica del mefedrone, dall'altro alla sua determinaszione in matrici biologiche con l'obiettivo di controllare nuove abitudini assuntiv