Mark Su

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.

Self-reported use of novel psychoactive substances in a US nationally representative survey: Prevalence, correlates, and a call for new survey methods to prevent underreporting.

BACKGROUND In recent years, there has been an increase in emergence and use of novel psychoactive substances (NPS) in the US and worldwide. However, there is little published epidemiological survey data estimating the prevalence of use in the US. METHOD Data on self-reported NPS use came from the National Survey of Drug Use and Health (2009-2013), a national representative sample of non-institutionalized individuals in the US. Subjects were asked to provide names of (non-traditional) drugs they used that they were not specifically asked about. We examined lifetime prevalence and sociodemographic correlates of self-reported use of new and uncommon synthetic drugs (NPS) among subjects ages 12-34-years-old. RESULTS 1.2% of subjects self-reported any use of the 57 NPS we examined. Use of psychedelic tryptamines (primarily DMT) was most common, followed by psychedelic phenethylamines (e.g., 2C series) and synthetic cannabinoids. Prevalence of self-reported use of NPS increased from 2009 to 2013 and use was most common among males, whites, older subjects, those of lower income, and among those residing in cities. Lifetime use of various other illicit drugs (e.g., LSD, cocaine, ecstasy/MDMA) was highly prevalent among NPS users. CONCLUSION This the first study reporting on use of a variety of NPS in a nationally representative US sample; however, use appears to be underreported as other national data suggest higher rates of NPS (e.g., synthetic cannabinoid) use. Developing more adaptable survey tools and systematically assessing NPS use would allow researchers to ask about hundreds of NPS and improve reporting as new drugs continue to rapidly emerge.

Characteristics of novel psychoactive substance exposures reported to New York City Poison Center, 2011-2014

ABSTRACT Background: Novel psychoactive substances (NPS) are emerging at an unprecedented rate. Likewise, prevalence of use and poisonings has increased in recent years. Objective: To compare characteristics of NPS exposures and non-NPS-drug-related exposures and to examine whether there are differences between exposures involving synthetic cannabinoid receptor agonists (SCRAs) and other NPS. Methods: Poison control center data from the five counties of New York City and Long Island were examined from 2011–2014. We examined prevalence and characteristics of NPS exposures (classified as intentional abuse) and compared characteristics of cases involving SCRAs and other NPS. Results: Prevalence of NPS exposures was 7.1% in 2011, rising to 12.6% in 2014. Most exposures (82.3%) involved SCRA use. The second and third most prevalent classes were phenethylamines/synthetic cathinones (“bath salts”; 10.2%) and psychedelic phenethylamines (4.3%). Compared to other drug-related exposures (i.e. involving licit and illicit drugs), those who used NPS were more likely to be younger, male, and to have not co-used other drugs (ps < 0.001). SCRA exposures increased sharply in 2014 and the mean age of users increased over time (p < 0.01). Females exposed to SCRAs were younger than males (p < 0.001), and in 2014, individuals exposed to SCRAs were more likely to report concomitant use of alcohol than users of other NPS (p = 0.010). Users of other NPS were more likely than SCRA users to report concomitant use of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)/“Molly” (p < 0.001). Conclusion: Exposures reported to the poison center that involve NPS are increasing and the majority involve SCRAs. These findings should inform prevention and harm reduction approaches.

Metabolism of classical cannabinoids and the synthetic cannabinoid JWH-018.

Although the putative pharmacological targets of synthetic cannabinoids (SCBs) abused in “K2” and “Spice” are similar to Δ9‐tetrahydrocannabinol (Δ9‐THC), it remains unclear why SCB toxicity is similar yet different from marijuana. There are obvious potency and efficacy differences, but also important metabolic differences that help explain the unique adverse reactions associated with SCBs. This brief review discusses the limited research on the metabolism of the SCB JWH‐018 and contrasts that with the metabolism of Δ9‐THC.

Thyroid Storm After Pediatric Levothyroxine Ingestion

A 2-year-old girl was found with an empty bottle of levothyroxine and blue coloring around her mouth. Forty tablets of 150-μg levothyroxine tablets were missing. Her 6-hour postingestion total thyroxine (T4) level was 68.1 μg/dL (normal range: 5–12 μg/dL), and her total triiodothyronine (T3) level was 472 ng/dL (normal range: 40–130 ng/dL). Serum levels of thyrotropin, T3, and T4 were then checked on days 3, 5, 7, and 10. On postingestion day 5, the child presented for follow-up with hyperthermia, vomiting, irritability, and increased lethargy. She was referred to the emergency department, where a heart rate of 220 beats per minute, a blood pressure of 130/80 mm Hg, and a temperature of 101°F were recorded. She also had multiple episodes of diarrhea. The patient was treated with oral propranolol (0.8 mg/kg) every 6 hours, intravenous normal saline, and ibuprofen; all her vital signs improved. Serial T3, T4, and thyrotropin serum levels were measured. Her total T3 levels were >800, 798, 445, 446, and 98 ng/dL on days 3, 5, 6, 9, and 13, respectively. Total T4 measurement was repeated on day 13, and the concentration was found to be 11.9 μg/dL. Her thyrotropin levels remained undetectable throughout the course of treatment. The patient was discharged from the hospital after a 4-day PICU stay, in good condition, on oral propranolol 0.8 mg/kg every 8 hours. Propranolol administration was discontinued 8 days after initiation with no further tachycardia, hypertension, or hyperthermia. The child tolerated the recommended regimen.

Amiodarone Attenuates Fluoride‐induced Hyperkalemia in Vitro

UNLABELLED Poisoning by hydrofluoric acid or fluoride salts results in hypocalcemia, hypomagnesemia, and hyperkalemia with subsequent cardiac dysrhythmias. In previous studies, quinidine attenuated fluoride-induced hyperkalemia in vitro, and enhanced survival in animals. Like quinidine, amiodarone is a potassium channel blocker, although amiodarone is more familiar to clinicians due to its recent inclusion in advanced cardiac life support (ACLS) protocols. OBJECTIVES This in-vitro study of human erythrocytes was designed to determine whether amiodarone could attenuate fluoride-induced hyperkalemia. METHODS Six healthy volunteers each donated 60 mL of blood on three occasions. Each specimen was divided into 12 tubes, incubated at 37 degrees C, and oxygenated with room air. An aqueous sodium fluoride (F(-)) solution was added to tubes 1-9. Incremental amounts of quinidine were added to tubes 1-4 (Q(1)-Q(4)) to attain calculated concentrations of 0.73 microg/mL, 1.45 microg/mL, 2.9 microg/mL, and 5.8 microg/mL, respectively. Incremental amounts of amiodarone were added to tubes 5-8 (A(1)-A(4)) to attain calculated concentrations of 0.38 microg/mL, 0.75 microg/mL, 1.5 microg/mL, and 3.0 microg/mL, respectively. Tubes 9-12 were controls for each of F(-), amiodarone, quinidine alone, and no additive, respectively. Extracellular potassium concentration ([K(+)]) was followed, and an objective endpoint was defined as the rise in potassium concentration at 6 hours. RESULTS Fluoride produced a significant change in [K(+)] by 6 hours in all samples. Quinidine produced a J-shaped curve in its ability to attenuate the rise in [K(+)], with only one concentration, Q(3), demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose-response effect, with statistical significance at A(1), A(2), and A(3) versus tube 9 (control). There was no significant difference among the effective concentrations (Q(3), A(1), A(2), and A(3)) of both drugs. CONCLUSIONS In this in-vitro model using human blood, amiodarone and quinidine both attenuated F(-)-induced hyperkalemia. Further study is indicated to determine whether amiodarone enhances survival in F(-)-poisoned animals.

Penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers

PURPOSE Two cases of penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angio-tensin II receptor blockers are reported. SUMMARY The first case of penile angioe-dema involved a 68-year-old man who arrived at the emergency department (ED) with a 2-12-hour history of penile swelling occurring three days after initiation of irbesartan in addition to longstanding lisinopril therapy. All parts of the physical examination were normal, except for the genital examination. The patients penis was edematous at midshaft only and was nontender with normal skin coloring. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking both lisinopril and irbesartan, and symptoms resolved within 48 hours with supportive care alone. In the second case, a 48-year-old man arrived at the ED complaining of penile swelling over the previous two days. Enalapril had been initiated one month before his arrival at the ED. The patients penis was nontender and edematous at midshaft. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking enalapril, given oral prednisone 60 mg, and asked to continue his prednisone for five days after discharge. The swelling resolved within two days of stopping enalapril, and he had no further episodes of penile swelling. Neither patient was rechallenged with the offending medications. CONCLUSION Penile angioedema was reported in two patients. The first case involved a patient receiving both lisinopril and irbesartan. The second patient was receiving enalapril only.

Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations.

Abstract Background: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. Case report: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. Conclusion: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.

Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuse

Abstract Background: Interest in tianeptine as a potential drug of abuse is increasing in the United States. We performed a retrospective study of calls to the New York State Poison Control Centers (PCCs) designed to characterize one state’s experience with tianeptine. Methods: Data were gathered from existing records utilizing the poison center data collection system, Toxicall® entered between 1 January 2000 through 1 April 2017. Information regarding patient demographics, reported dose and formulation of tianeptine, reported coingestants, brief narrative description of the case, disposition, and case outcome was collected. Results: There were nine reported cases of tianeptine exposure. Seven were male with a mean age of 27. Three reported therapeutic use of tianeptine and five reported intentional abuse. One case was an unintentional pediatric exposure. Doses were reported in three cases; 12.5 mg in a pediatric unintentional exposure, and 5 and 10 g daily in the two reports of intentional abuse. Of note, five patients complained of symptoms consistent with opioid withdrawal. In one of two cases in which naloxone was administered, an improvement in mental status and the respiratory drive was noted. Outcomes reported in Toxicall® were minor in two cases, moderate in five cases, major in one case, and not reported in one case. Conclusions: These cases, reported to the New York State PCCs should alert readers to the potential for tianeptine abuse, dependence, and withdrawal.

Troponin elevations and organophosphate poisoning: Direct cardiac injury or demand ischemia?

We have read with interest the study by Y.S. Cha and colleagues investigating organophosphate (OP) poisoning and myocardial injury. 1 The authors conclude that OP poisoning can cause direct myocardial injury during the acute phase of poisoning as well as that trending serum troponin I concentration may be needed in severe OP poisoning. However, these data presented from this retrospective study raise some questions as to the author ’ s interpretation. Based on 34% of their subjects having elevated troponin I concentration, the authors conclude that severe OP poisoning can cause direct myocardial injury. The highest troponin I level reached was 2.33 ng/ml and the mean elevation was only 0.305 ng/ml. These seemingly trivial elevations make it diffi cult to determine the relationship of OP poisoning as a cause of direct myocardial injury. Rather, these elevations could be related to demand ischemia and “ troponin leak ” in severely poisoned patients. Furthermore, were there any overt signs of cardiac injury or clinical signifi cance to this troponin elevation? Only 26% of these patients with elevated troponins experienced hypotension, and there was no statistical difference in B-type natriuretic peptide (BNP) concentrations, suggesting that the patients did not have acute heart failure. The patients found to have troponin I elevations were different in a number of pertinent demographic variables. Namely, those patients with troponin I elevations were older, had a lower initial Glasgow Coma Scale (GCS), higher Namba classifi cation, a higher incidence of mechanical ventilation, and higher rates of pneumonia. These patient discrepancies would simply indicate that a more severely ill patient population is more likely to have elevations in troponin I. Multiple studies have demonstrated elevated troponin I levels in critically ill patients without acute coronary syndromes (ACS), suggesting that sepsis and other systemic infl ammatory response syndrome (SIRS)-related disease processes account for these elevations. 2 – 4 Here, the authors found no statistical signifi cance in the difference between the two groups with respect to sepsis; however, they did not discuss how they controlled for this specifi c variable. Also, only 18.2% of patients had troponin I elevations on initial presentation suggesting that other confounding variables while in hospital may have attributed to the remainder of troponin I elevations. Moreover, previous studies have shown that mechanical ventilation alone increases mortality in critically ill patients with suggested myocardial injury. 5