Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications.

OBJECTIVE: Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. METHODS: We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. RESULTS: There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180-4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3-18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12-31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. CONCLUSION: Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Current and Potential Roles in Sports Pharmacy: A Systematic Review.

(1) Background: The objective of this systematic review was to evaluate current and potential roles for pharmacists in sports medicine and to identify key themes in outcomes reported in studies. (2) Methods: EMBASE, MEDLINE, CINAHL, Scopus and the Cochrane Library were searched in January 2019. Peer-reviewed, original research articles were considered for inclusion. Articles published in a language other than English were excluded. Quality appraisal was performed independently by two authors. (3) Results: Findings of 11 eligible articles (10 observational and 1 experimental study design) were grouped into three themes: (i) doping prevention and control, (ii) injury management and first aid, and (iii) educational and curricular needs. Pharmacists were perceived as a good potential source of information about doping and are enthusiastic about counseling athletes, but lack knowledge and confidence in this area. While pharmacists were frequently consulted for advice on managing sprains and strains, their advice was not always guided by current evidence. Pharmacists and pharmacy students recalled limited opportunity for education in sports pharmacy. (4) Conclusion: Pharmacists showed a willingness and an aptitude to counsel athletes. However, lack of knowledge and confidence, and limited educational opportunities, were key barriers. More research is necessary to support pharmacists in this role.

Simulation and Feedback in Health Education: A Mixed Methods Study Comparing Three Simulation Modalities.

Background. There are numerous approaches to simulating a patient encounter in pharmacy education. However, little direct comparison between these approaches has been undertaken. Our objective was to investigate student experiences, satisfaction, and feedback preferences between three scenario simulation modalities (paper-, actor-, and computer-based). Methods. We conducted a mixed methods study with randomized cross-over of simulation modalities on final-year Australian graduate-entry Master of Pharmacy students. Participants completed case-based scenarios within each of three simulation modalities, with feedback provided at the completion of each scenario in a format corresponding to each simulation modality. A post-simulation questionnaire collected qualitative and quantitative responses pertaining to participant satisfaction, experiences, and feedback preferences. Results. Participants reported similar levels satisfaction across all three modalities. However, each modality resulted in unique positive and negative experiences, such as student disengagement with paper-based scenarios. Conclusion. Importantly, the themes of guidance and opportunity for peer discussion underlie the best forms of feedback for students. The provision of feedback following simulation should be carefully considered and delivered, with all three simulation modalities producing both positive and negative experiences in regard to their feedback format.

The pharmacokinetics and pharmacodynamics of severe aldicarb toxicity after overdose.

OBJECTIVE: To describe the clinical effects, pharmacokinetics, and pharmacodynamics of plasma and acetylcholinesterase in an aldicarb overdose. CASE REPORT: A 57-year-old female was found unconscious and incontinent of urine after ingesting aldicarb. She was bradycardic, hypotensive, hypersalivating, clammy, had small pupils, and generalized weakness. She was intubated, ventilated, and treated with large atropine doses (50 mg and 20 mg/h infusion) and adrenaline. She improved hemodynamically over 24 h, but remained comatose for another 24 h, before recovering without sequela. Aldicarb concentration at admission was 2.18 µg/ml and concentration-time data best fitted a two compartmental model with first order absorption and a time of ingestion 4.5 h preadmission. The half-life of distribution was 0.4 h and half-life of elimination, 13 h. Plasma cholinesterase concentration at admission was 0.3 kU/L (Reference range[RR]:4.3-10.6 kU/L) and red cell cholinesterase was 10 U/gHb (RR:38-66 U/gHb). The IC50 was 0.15 µg/ml and 0.26 µg/ml for plasma and red cell cholinesterase, respectively. DISCUSSION: Aldicarb poisoning causes rapid onset severe toxicity with muscarinic and nicotinic excess, seizures, and decreased consciousness. Cholinesterases rapidly recover once aldicarb concentrations decrease and precede clinical recovery.

The pharmacokinetics of sertraline in overdose and the effect of activated charcoal.

AIMS: To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC). METHODS: Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose. RESULTS: There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250-5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h(-1) , 5340 l and 130 l h(-1) , respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4-30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (Cmax ). CONCLUSIONS: Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.

Neuroleptic malignant syndrome or a statin drug reaction? A case report.

A 60-year-old woman with a long psychiatric history presented with delirium and mutism. She was febrile, with marked limb rigidity and elevated creatinine kinase (CK) level. Current medications included pericyazine. Current or recent use of dopamine-blocking agents, such as pericyazine, together with a disturbance in conscious state, autonomic dysfunction, and an elevated CK level may be suggestive of neuroleptic malignant syndrome (NMS). The diagnosis was confirmed as NMS, and she was successfully treated with bromocriptine. Eight years later, she represents with symptoms suggesting recurrence of NMS including elevated CK level and myalgia, however, without limb rigidity. Current medications include quetiapine, lithium, simvastatin, and a recent course of clarithromycin. Macrolide antibiotics such as clarithromycin inhibit the metabolic pathway of statins via the cytochrome CYP450 3A4 hepatic enzyme system and may result in elevated CK level, myopathy, or rhabdomyolysis producing symptoms that may be confused with NMS. Simvastatin was ceased with rapid decrease in CK level and resolution of symptoms. This case highlights the importance of considering other diagnoses in any patient presenting with a disturbance in conscious state, autonomic dysfunction, and an elevated CK level. Particularly in a patient with a history of NMS, a thorough medication history is essential to aid diagnosis and avoid confusion with presenting symptoms and medical history.