Nicholas Nacca

The synthetic cannabinoid withdrawal syndrome.

Background:Little is known about the effects of synthetic cannabinoids. There has been only one previous report of a withdrawal syndrome from synthetic cannabinoids. We report two cases of a withdrawal syndrome from prolonged habitual use of synthetic cannabinoids. Discussion:Withdrawal from delta-9-THC has been described as a syndrome of anxiety, myalgias, chills, and anorexia. Synthetic cannabinoids are potent than delta-9-THC and thus the withdrawal syndrome is similar but more severe; however the symptoms do not seem to improve with delta-9-THC. The differences in presentation could be due to the fact that synthetic products may contain several heterogeneous compounds, including amphetamine-like substances. Conclusions:The acute withdrawal syndrome appears to be characterized mainly by anxiety and tachycardia in the absence of any neurological findings or electrolyte disturbances. We describe two patients with symptoms consistent with withdrawal presumably due to synthetic cannabinoid use. The most appropriate treatment for such patients remains unknown, however benzodiazepines are a reasonable first line approach and quetiapine may have some efficacy.

Loperamide toxicokinetics: serum concentrations in the overdose setting

A web-based study published in 2013 suggested that loperamide was being abused to attenuate the symptoms of opioid withdrawal.1 Marraffa et al recently reported a case series of patients who presented with cardiac conduction disturbances after loperamide abuse.2 This case series outlined the clinical course of 5 patients, 3 of whom experienced life-threatening arrhythmias. Isolated serum levels were reported in four of these patients. We report a subsequent hospitalization and pharmacokinetic profile of one of the patients in the case series.2 A 30-year-old male presented to an outlying facility for a syncopal episode. The initial electrocardiogram (ECG) revealed a heart rate of 60 beats per minute, a QRS measurement of 192 ms, and a QT of 704 ms. He left against medical advice, only to be found pulseless and apneic by a family member hours later. He was brought back to the outlying facility and demonstrated multiple ventricular arrhythmias, including one episode of polymorphic ventricular tachycardia. He was transferred to our facility after being defibrillated multiple times. The patient reported that he had resumed his abuse of loperamide and had been taking two hundred 2-mg tablets daily for the last seven days. He has had at least four prior hospitalizations with a similar presentation associated with loperamide abuse. The patient’s cardiac conduction disturbance was managed with a continuous infusion of isoproterenol. The conduction disturbance slowly resolved with a QRS of 96 ms and QTc of 489 ms on hospital day 9. He was discharged to an inpatient psychiatric facility on hospital day 13 with a QRS of 94 ms and a QT/QTc of 406/483 ms. Due to his prolonged toxicity we obtained serum loperamide concentrations at multiple time points to better understand his pharmacokinetic profile. The reported pharmacokinetic half-life of loperamide is approximately 9–13 h, although longer half lives up to about 40.9 h have been reported with doses of 16 mg in healthy volunteer studies.3–4 The toxicokinetics of loperamide have not been previously reported. The patient presented to our facility 20 h after his last reported 400-mg dose. On presentation his loperamide level was 120 ng/mL. His loperamide serum levels 32, 44, 57, and 70.5 h post-ingestion were 47 ng/mL, 30 ng/mL, 30 ng/mL, and 20 ng/mL, respectively (Figure 1). Published peak loperamide concentrations after doses of 2–16 mg were reported to be between 0.24 and 3.1 ng/mL and occurred 4–5.9 h after administration.5–6 His first two serum concentrations demonstrated an initial decline consistent with the reported half-life based on population kinetics (8.9 h). However, subsequent serum concentrations demonstrated a half-life of approximately 34.8 h. Interpretation of this kinetic data is complicated by the patient’s history of Crohn’s disease, multiple small bowel resections, and ileostomy. Additionally, the patient did receive a single dose of buprenorphine 12 mg sublingually and amiodarone 150 mg intravenously 35 and 38 h after his reported ingestion, respectively. No other cytochrome P450 inhibitors or inducers were given during the time frame when serum concentrations were drawn. A comprehensive drug panel including synthetic cannabinoids and designer drugs conducted on urine by NMS Labs was negative. Our patient’s ECG changes are consistent with previously published case reports.2,7 The elimination half-life observed in our patient is not consistent with the reported half-life. Loperamide is a m-receptor agonist, which may reduce gastrointestinal motility and result in delayed absorption of drug.8 Delayed absorption in the overdose setting may result in prolonged toxicity. Loperamide has also been reported to antagonize calcium channels, which may result in reduced gastrointestinal motility.9 The elimination kinetics of loperamide are not known in the overdose setting and a multicompartment pharmacokinetic model cannot be excluded. Our patient also received medications that inhibit both cytochrome P450 3A4 and 2D6 enzymatic metabolism. These enzyme families are reported to play a role in the hepatic conversion of loperamide to the N-demethyl metabolite, and inhibition might have further slowed the elimination of parent drug.10 Genetic alterations in these enzymatic pathways could also alter the kinetics of loperamide, which may explain the wide range in half-lives reported in one pharmacokinetic study.3 It is unclear what, if any, impact the patient’s altered gastrointestinal tract may have had on the kinetics of loperamide. Further kinetic studies are needed to assess the toxicokinetics of loperamide.

Severe amiodarone induced pulmonary toxicity

A known complication of Amiodarone therapy is Amiodarone induced Pulmonary Toxicity (APT). Several features of this adverse effect make it difficult to diagnosis and treat. The case of a 63-year-old male with classic radiographic and histologic findings of APT is discussed. Clinical presentation, pathophysiology, diagnostic findings, and treatment strategies are reviewed. The patient was successfully managed with pulse high dose steroid therapy.

Pediatric death after unintentional exposure to liquid nicotine for an electronic cigarette

Sir,Refillable electronic-cigarettes (e-cigarettes) continue to grow in popularity with the global e-cigarette market reaching an estimated worth of

Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor

6 billion in 2014.[1] E-cigarette liquid formul...

In response to: “Loperamide metabolite-induced cardiomyopathy and QTc prolongation”

Abstract Metaxalone has only recently been associated with serotonin syndrome. The mechanism of action of this centrally acting muscle relaxant is unknown; however, the observation of serotonin syndrome in patients with metaxalone overdose suggests a role in the serotonergic pathway. Case report. (Case 1) A 29-year-old woman with overdose of metaxalone presented to the emergency department with altered mental status, seizure-like activity, hyperthermia, rigidity in the lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 168/80 mmHg, heart rate of 208 beats per minute (bpm), respirations of 20/min, a temperature of 41.6° C rectally, and room air oxygen saturation of 97%. She was intubated and sedated with benzodiazepines, and actively cooled. Serum paroxetine concentration was 23 (therapeutic range: 20–200) ng/mL, and serum metaxalone concentration was 31 mcg/mL (peak plasma concentrations average 0.9 mcg/mL at 3.3 h following a single oral dose of 400 mg). (Case 2) A 27-year-old man presented to the emergency department with altered mental status, rigidity in his lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 158/131 mmHg, heart rate of 126 bpm, respiratory rate of 20 breaths per minute, and temperature of 37.2°C, with oxygen saturation of 98% on room air. His medication list included metaxalone and escitalopram. He was managed aggressively with IV boluses of diazepam, in total 80 mg, in the emergency department. Serum escitalopram concentration was 24 ng/mL with a therapeutic range of 21–64 ng/mL, and serum metaxalone concentration was 58 mcg/mL. Conclusion. These two cases suggest that at supratherapeutic concentrations metaxalone has serotonergic effects. Severe serotonin toxicity may result from metaxalone abuse in individuals using a selective serotonin reuptake inhibitor therapeutically.

Are those Premature Ventricular Complexes

We appreciate Bhatti et al.’s [1] thoughtful presentation and discussion of cardiac conduction disturbance and cardiomyopathy after a reported loperamide overdose. We agree that desmethylloperamide may play a role in the development of cardiac toxicity [2–5]. We were also involved in this patient’s care. We recognize the limitations of case reports especially with restrictions to word count and the difficulty in reporting all of the details of a particular case. There are, however, several details that we feel should be included, as they may, or may not alter the reader’s conclusions regarding the potential of desmethylloperamide to independently cause the reported toxicity. The patient presented to the Emergency Department after being found unresponsive by her husband. Pre-hospital naloxone was administered resulting in the patient becoming acutely agitated requiring physical restraints and haloperidol. She reported insufflating oxycodone immediately prior to her presentation and overdosing on loperamide, although the time frame of this ingestion was unclear. It is unclear to what degree the acute precipitated withdrawal contributed to the patient’s stress cardiomyopathy. She denied acute overdose of any other medications, but was also prescribed olanzapine, trazodone, and venlafaxine. The involvement of these medications and their contribution to the reported electrocardiogram (ECG) abnormalities is unknown. The ECG obtained on admission did demonstrate QTc prolongation to 544ms (automated measurement, Bazett’s formula) and her QTc prolongation persisted for >96 h. The ECG presented as Figure 1 in the case report was obtained approximately 46 h after the patient presented and 42 h after her serum loperamide and desmethylloperamide sample was collected. Unfortunately, loperamide and desmethylloperamide serum concentrations were only obtained at the time of hospital presentation. Cardiac dysrhythmias are described in the setting of loperamide abuse, but the activity and pharmacokinetics of the metabolite are not described [4]. It is imperative that clinicians obtain serum concentrations of both parent drug and metabolite in order to correlate concentrations with toxicity. We encourage clinicians and researchers to continue to formulate hypotheses and undertake investigation into the mechanisms of loperamide and desmethylloperamide, their effects on cardiac potassium currents, and other mechanisms that may contribute to toxicity. Loperamide toxicity remains in its infancy and there are still more questions than answers.

Nausea, vomiting, and diarrhea in a 9-year-old girl.

Ventricular parasystole has been known to be a benign rhythm. We present a case of a 53-year-old man with chest pain and ventricular parasystole on electrocardiogram upon initial presentation. He was admitted and found to have normal serial cardiac enzymes and nuclear stress testing. He was discharged home with primary care follow-up. We highlight this case, as ventricular parasystole has been shown to be associated with cardiovascular disease and is a rhythm that should not be ignored. Our review of the literature shows that a thorough cardiovascular investigation should take place when this rhythm is identified.

Hematocolpos secondary to imperforate hymen

Cryptosporidiosis is reported in an otherwise healthy child. Her history was significant for playing in natural waters during a camping trip 1 week prior. Several days later, she began improving despite an incorrect diagnosis and inappropriate antibiotic therapy. Nitazoxanide was given once the diagnosis was established. Obtaining a thorough patient history, administering appropriate antibiotics, and counseling patients on preventive measures are critical steps in treating and managing the transmission of this parasite. The case emphasizes the value of stool ova and parasite examination for proper diagnosis of pediatric diarrheal illness in the emergency setting. In addition, the often overlooked diagnosis of cryptosporidiosis is reviewed as an important cause of diarrheal illness in the immunocompetent pediatric population.