Joyce Cooper

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.

Desvenlafaxine overdose and the occurrence of serotonin toxicity, seizures and cardiovascular effects

Abstract Context: Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose. Objective: We aimed at investigating the clinical effects and complications from desvenlafaxine overdose. Materials and methods: This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose. Results: There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13–68 years) with a median ingested dose of 800 mg (range: 250–3500 mg; interquartile range (IQR): 600–1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13–14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] > 140–180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS >120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants. Conclusion: Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT2A receptor

Serotonin toxicity results from serotonin excess in the central nervous system from serotonergic drugs. Previous studies suggest an association between T102C polymorphism of the serotonin 2A (5-hydroxytryptamine 2A) receptor gene and serotonergic adverse effects with serotonergic drugs. We aimed to determine whether there is an association between the T102C polymorphism and serotonin toxicity in patients taking serotonergic drug overdoses. Ninety-five patients presenting with serotonergic drug overdoses were examined for serotonin toxicity and had blood collected for DNA analysis. A diagnosis of serotonin toxicity was made in 14 patients (15%) based on the Hunter Serotonin Toxicology Criteria. Four of the 14 patients (29%) with serotonin toxicity had the C/C genotype compared with 20/81 (25%) without serotonin toxicity. There were no differences in age or sex, but the median defined daily dose taken by patients with serotonin toxicity was 27 (14–84) compared with 18 (2–136) in patients without serotonin toxicity (P=0.06). There was no association between serotonin toxicity and the T102C polymorphism in patients taking a serotonergic drug overdose.

Gamification for Education: Designing a Pharmacy Education Game

A key motivator for the use of serious games has been the notion that “gamification” provides users with an additional level of engagement. This study examines a traditional model of usability in terms of engagement and efficacy, presenting the results obtained from a formative evaluation of a serious game prototype that has been developed to assist in pharmacy education.

Providing medicines information and education to hospital in-patients: patients' experiences and preferences

Providing medicines information and counselling to hospital in‐patients is one of the many daily tasks of hospital pharmacists; however, there is a lack of evidence relating to the expectations of patients around medicines information and education in the hospital setting.

Zero-order metoprolol pharmacokinetics after therapeutic doses: severe toxicity and cardiogenic shock

Abstract Objective: Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment. Case details: A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250 mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10 U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76 L/min/m2). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX® vs 4.3 (www.lixoft.com). Admission metoprolol concentration was 2.39 μg/mL (therapeutic reference range: 0.035–0.5 μg/mL). Data best fitted a one compartmental model with Michaelis–Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4 L, maximum rate [Vm], 9.57 mg h−1, Michaelis constant [Km], 1.97 mg L−1. Predicted elimination half-life decreased from 20 h over time until there was first order elimination with a half-life 9 h. Conclusion: The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes.

The pharmacokinetics and pharmacodynamics of severe aldicarb toxicity after overdose

Abstract 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.

Comparing Animation with Video For Teaching Communication Skills

In this paper, we describe a case study that compares the use of animation and video for teaching communication skills to pharmacy students. We present an appropriate framework outlining the key communication criteria that were used to develop a three part, patient-pharmacist communication scenario. This scenario was scripted, filmed in a community pharmacy, and edited into a six minute sequence before being converted to an equivalent animation sequence by using digital filters. Both the video and animation were compared in a usability trial using 37 students studying pharmacy. These students were divided into two groups, each experiencing either the video or animation sequence before being asked to provide subjective feedback of the usefulness of the approach for teaching communication. Both the video and animation group provided equivalent positive feedback about the approach. The two groups then experienced the alternative representation, either video or animation and were asked to nominate a preference. Both groups indicated a significant preference for the video presentation. It is recognized that the design and style of the animation may impact on the general validity of these outcomes and as such the paper also provides a detailed discussion of relevant design issues.

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.