Unilateral mydriasis following septoplasty with inferior turbinate reduction.

Nasal septoplasty and inferior turbinate reduction are common procedures performed in the treatment of nasal obstruction. These procedures are generally considered to be safe with minimal reported complications. Herein, we describe a case of a 43-year-old female who developed transient unilateral mydriasis following septoplasty with inferior turbinate reduction, likely due to the sympathomimetic agents used for vasoconstriction and mucosal decongestion.

Acute and chronic sympathomimetic effects of e-cigarette and tobacco cigarette smoking: role of nicotine and non-nicotine constituents.

Electronic cigarettes (ECs) and tobacco cigarettes (TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability (HRV) and hemodynamics would be similar in chronic EC and TC smokers and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine, constituents in EC aerosol. In 100 smokers, including 58 chronic EC users and 42 TC smokers, baseline HRV and hemodynamics [blood pressure (BP) and heart rate (HR)] were compared. To isolate the acute effects of nicotine vs. non-nicotine constituents in EC aerosol, we compared changes in HRV, BP, and HR in EC users after using an EC with nicotine (ECN), EC without nicotine (EC0), nicotine inhaler (NI), or sham vaping (control). Outcomes were also compared with TC smokers after smoking one TC. Baseline HRV and hemodynamics were not different in chronic EC users and TC smokers. In EC users, BP and HR, but not HRV outcomes, increased only after using the ECN, consistent with a nicotine effect on BP and HR. Similarly, in TC smokers, BP and HR but not HRV outcomes increased after smoking one TC. Despite a similar increase in nicotine, the hemodynamic increases were significantly greater after TC smokers smoked one TC compared with the increases after EC users used the ECN. In conclusion, chronic EC and TC smokers exhibit a similar pattern of baseline HRV. Acute increases in BP and HR in EC users are attributable to nicotine, not non-nicotine, constituents in EC aerosol. The greater acute pressor effects after TC compared with ECN may be attributable to non-nicotine, combusted constituents in TC smoke.NEW & NOTEWORTHY Chronic electronic cigarette (EC) users and tobacco cigarette (TC) smokers exhibit a similar level of sympathetic nerve activity as estimated by heart rate variability. Acute increases in blood pressure (BP) and heart rate in EC users are attribute to nicotine, not non-nicotine, constituents in EC aerosol. Acute TC smoking increased BP significantly more than acute EC use, despite similar increases in plasma nicotine, suggestive of additional adverse vascular effects attributable to combusted, non-nicotine constituents in TC smoke.

Safety of Intradermal/Subcutaneous Lidocaine With Epinephrine Use in Dermatologic Surgery.

BACKGROUND: Recently, the safety of lidocaine plus epinephrine use in outpatient surgery has come under scrutiny despite its long history of use in outpatient dermatologic procedures and surgeries. OBJECTIVE: To assess the frequency of crash cart and other emergency interventions during Mohs micrographic surgery when lidocaine plus epinephrine is used as a local anesthetic and evaluate patient comorbidities associated with these events. MATERIALS AND METHODS: A retrospective chart review was conducted in an outpatient Mohs micrographic surgery clinic. RESULTS: One thousand one hundred twenty-seven Mohs cases were reviewed from the period of March 2015 to June 2016 with 864 meeting the inclusion criteria of patient weight, medical history, and amount of lidocaine administered recorded. No adverse events requiring emergency intervention with a crash cart or transfer to the emergency department occurred despite a patient population with advanced age and a wide range of comorbidities. CONCLUSION: No serious adverse events requiring emergency intervention were associated with lidocaine with epinephrine doses administered below the Food and Drug Administration recommended maximum. The authors did not find evidence from this study or after a literature search to support the requirement for a crash cart and other emergency equipment to be present during procedures.

The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase II study SAKK 33/14.

The ß-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F-positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a ß-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F-positive patients with myeloproliferative neoplasms and a mutant allele burden more than 20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary end point was reduction of JAK2-V617F allele burden of 50% or over, but this was not reached in any of the patients. One patient achieved a 25% reduction in JAK2-V617F allele burden by 24 weeks. A small subgroup of patients showed hematologic improvement. As a side study, bone marrow biopsies were evaluated in 20 patients. We found an increase in the nestin+ cells from a median of 1.09 (interquartile range 0.38-3.27)/mm2 to 3.95 (interquartile range 1.98-8.79)/mm2 (P<0.0001) and a slight decrease of reticulin fibrosis from a median grade of 1.0 (interquartile range 0-3) to 0.5 (interquartile range 0-2) (P=0.01) between start and end of mirabegron treatment. Despite the fact that the primary end point of reducing JAK2-V617F allele burden was not reached, the observed effects on nestin+ mesenchymal stem cells and reticulin fibrosis is encouraging, and shows that mirabegron can modify the microenvironment where the JAK2-mutant stem cells are maintained. (Registered at clinicaltrials.gov identifier: 02311569).

Sympathomimetic Toxidromes and Other Pharmacological Causes of Acute Hypertension.

PURPOSE OF REVIEW: Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. RECENT FINDINGS: We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.

Drug-Induced Hypertension: Focus on Mechanisms and Management.

PURPOSE OF REVIEW: This review is intended to briefly describe the primary mechanistic pathways by which several common drugs can increase blood pressure. We also propose potential management strategies based on the underlying mechanisms responsible for the blood pressure elevation. RECENT FINDINGS: As hypertension is a significant risk factor for cardiovascular events, healthcare providers must evaluate patients' concomitant medications that may contribute to elevations in blood pressure. The presence of these medications, if not properly addressed, can lead to consequences such as an inadvertent diagnosis of hypertension, as well as the potential need for unnecessary intensification of antihypertensive regimens in those already treated. Blood pressure elevation is an unfortunate by-product of multiple medications. The substances discussed in this review can elicit significant and persistent elevations in blood pressure, and health care providers must first evaluate whether the drug is necessary. If one exists, it is best to select a similar agent with lower risk of increasing blood pressure; if unavoidable, then clinicians should select an appropriate management strategy to compensate for the rise in blood pressure.

Impact of Functional Group Modifications on Designer Phenethylamine Induced Hyperthermia.

The popularity of designer phenethylamines such as synthetic cathinones ("bath salts") has led to increased reports of life-threatening hyperthermia. The diversity of chemical modifications has resulted in the toxicological profile of most synthetic cathinones being mostly uncharacterized. Here, we investigated the thermogenic effects of six recently identified designer phenethylamines (4-methylmethamphetamine, methylone, mephedrone, butylone, pentylone, and MDPV) and compared these effects to the established thermogenic agent 3,4-methylenedioxymethamphetamine (MDMA). Specifically, we determined the impact of a ß-ketone, α-alkyl, or pyrrolidine functional group on core-body temperature changes. Sprague-Dawley rats (n = 5-6) were administered a dose (30 mg/kg, sc) of a designer phenethylamine or MDMA, and core body temperature measurements were recorded at 30 min intervals for 150 min post treatment. MDMA elicited the greatest maximum temperature change (ΔTmax), and this effect was significantly greater than that of its ß-ketone analogue, methylone. Temperature-area under the curves (TAUCs) and ΔTmax were also significantly different between 4-methylmethamphetamine (4-MMA) and its ß-ketone analogue mephedrone. Lengthening the α-alkyl chain of methylone to produce butylone and pentylone significantly attenuated the thermogenic response on both TAUCs and ΔTmax compared to those of methylone; however, butylone and pentylone were not different from each other. Pyrrolidine substitution on the N-terminus of pentylone produces 3,4-methylenedioxypyrovalerone (MDPV), which did not significantly alter core body temperature. Thermogenic comparisons of MDMA vs methylone and 4-MMA vs mephedrone indicate that oxidation at the benzylic position significantly attenuates the hyperthermic response. Furthermore, either extending the α-alkyl chain to ethyl and propyl (butylone and pentylone, respectively) or extending the α-alkyl chain and adding a pyrrolidine on the N-terminus (MDPV) significantly blunted the thermogenic effects of methylone. Overall, the present study provides the first structure-activity relationship in vivo toxicological analysis of designer phenethylamines.

Diffuse cerebrovascular dilation: Case report of amezinium metilsulfate-induced reversible cerebral vasoconstriction syndrome.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches with reversible cerebral vasoconstriction, and often precipitated by the postpartum state and vasoactive medications. We describe a case of a patient with RCVS induced by amezinium metilsulfate, a sympathomimetic drug, in whom magnetic resonance angiography (MRA) initially revealed diffusely dilated cerebral arteries. CASE DESCRIPTION: A 34-year-old woman was prescribed amezinium metilsulfate for hypotension. Twelve days later, she suffered from abrupt severe headaches and was referred to our department. She had no neurological deficits; however, MRA revealed diffusely dilated anterior, middle, and posterior cerebral arteries with vasoconstriction. She was tentatively diagnosed with RCVS and successfully treated with verapamil for headache. Nevertheless, follow-up MRAs disclosed widespread segmental vasoconstriction that resolved in two months. DISCUSSION: Diffuse cerebrovascular dilation has not been addressed but may be associated with RCVS pathophysiology. In addition, physicians should bear in mind that amezinium metilsulfate can potentially induce RCVS.

Peripheral vasoconstriction induced by ß-adrenoceptor blockers: a systematic review and a network meta-analysis.

AIM: Peripheral vasoconstriction has long been described as a vascular adverse effect of ß-adrenoceptor blockers. Whether ß-adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to ß1 -adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta-analysis in order to assess the comparative risk of peripheral vasoconstriction of different ß-adrenoceptor blockers. METHOD: We searched for randomized controlled trials (RCTs) including ß-adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of ß-adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the ß-adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374). RESULTS: Among 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with ß-adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not. CONCLUSION: Our results suggest that ß-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to ß1 -adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra-indications of use of ß-adrenoceptor blockers and suggest that ß-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.

Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study.

BACKGROUND: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva; (2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. METHODS: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. RESULTS: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p < 0.001), lower pH-values of their saliva (p < 0.001) and more bruxism symptoms (p < 0.001). However, we found no relevant trismus symptoms on comparing the two groups (p > 0.05). CONCLUSIONS: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms.

Sympathomimetic decongestants during pregnancy: risks for the unborn child.

In addition to the risk of cardiovascular events and neurological disorders, sympathomimetic decongestants have teratogenic potential, albeit weak, when taken during the first trimester of pregnancy, probably through disruption of the vascular system of the embryo and the pregnant woman. In the second and third trimesters of pregnancy, the fetus is exposed to the same adverse effects as the mother.

Radiology Department Preparedness for the Management of Severe Acute Iodinated Contrast Reactions: Do We Need to Change Our Approach?

OBJECTIVE: The purpose of this study was to identify opportunities for reducing epinephrine administration errors after a sentinel event entailing an overdose of i.v. epinephrine occurred in a radiology department. MATERIALS AND METHODS: A root cause analysis was performed that included review and analysis of current system protocols, a medication audit, and access to treatment algorithms. A proctored three-question multiple-choice test was administered to radiology attending physicians, fellows, residents, and nurses to gauge baseline knowledge of epinephrine use. Chi-square analysis was performed. RESULTS: Twelve of 13 radiology department central pharmacy automation system locations lacked epinephrine ampules. As a result, personnel had to access i.v. epinephrine stocked on hospital code carts designed for use during cardiac arrest. This led to errors related to appropriate dosing. Test participants included 46 attending physicians, 23 fellows, 28 residents, and 25 nurses (n = 122). Almost all (99%) correctly identified epinephrine as the medication to administer in this situation. Approximately one half (52%) correctly identified the dose of intramuscular epinephrine, but only 29% knew the dose and rate of administration of i.v. epinephrine (p < 0.001). Attending physicians were more likely to administer i.v. epinephrine correctly than were the other groups (p < 0.0001). CONCLUSION: Stocking and routine auditing of medication availability are essential. The use of epinephrine intended for cardiac arrest stocked on code carts should be avoided during contrast reactions. It would be optimal if first-line responders to contrast reactions included attending physicians, but this may not always be the case at academic institutions.

A case of suicide by self-injection of adrenaline.

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Intracerebral hemorrhage associated with oral phenylephrine use: a case report and review of the literature.

BACKGROUND: Prior reports have linked both ischemic and hemorrhagic stroke to use of sympathomimetic drugs including phenylephrine. The purpose of this study is to describe the first case, to our knowledge of intracerebral hemorrhage (ICH) after oral use of phenylephrine and to systematically review the literature on phenylephrine and acute stroke. METHODS: A case report and review of the literature. RESULTS: A 59-year-old female presented with thunderclap headache, right hemiparesis, aphasia, and left gaze deviation. Head computed tomography (CT) showed a left frontal ICH with intraventricular and subarachnoid extension. She had no significant past medical history. For the previous 30 days, the patient was taking multiple common cold remedies containing phenylephrine to treat sinusitis. CT and magnetic resonance angiography showed no causative vascular abnormality. Catheter cerebral angiography supported reversible cerebral vasoconstriction syndrome (RCVS). Phenylephrine was determined to be the most likely etiology for her hemorrhage. A review of the literature, found 7 cases describing phenylephrine use with acute stroke occurrence: female, 5 of 7 (71%); route of administration, nasal (n = 3), ophthalmic (n = 2), intravenous (n = 1), intracorporeal injection (n = 1). Stroke types were subarachnoid hemorrhage (n = 5), ICH (n = 4), and ischemic (n = 1). One case reported RCVS after phenylephrine use. CONCLUSIONS: It is scientifically plausible that phenylephrine may cause strokes, consistent with the pharmacologic properties and adverse event profiles of similar amphetamine-like sympathomimetics. As RCVS has been well described in association with over-the-counter sympathomimetics, a likely, although not definitive, causal relationship between phenylephrine and ICH is proposed.

Persistent wandering atrial pacemaker after epinephrine overdosing - a case report.

BACKGROUND: Long-term complications of sympathomimetic drug overdosing have not been adequately investigated in infants and young children. Despite reports discouraging their use in children, these formulations are frequently administered for "cold-like symptoms". Their frequent adverse events are different forms of arrhythmias, including multifocal atrial tachycardia. CASE PRESENTATION: A 3-year-old toddler developed multifocal atrial tachycardia following an iatrogenic overdose of epinephrine accidentally administered intravenously. His ECG showed wandering atrial pacemaker (p-waves with different origins and configurations) that persisted for at least one year. This event demonstrated the sensitivity of young children to the sympathomimetic drugs, especially overdosing. CONCLUSIONS: Health care providers and parents should be warned of toxicities associated with sympathomimetic drug overdosing. Future studies are needed to determine whether wandering atrial pacemaker is a potential long-term complication of high-dose sympathomimetics.

Drug-induced takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC), also known as stress cardiomyopathy, is an increasingly recognized clinical syndrome of acute reversible left ventricular dysfunction precipitated by intense emotional or physical stress. Excessive sympathetic stimulation is believed to be central to the pathogenesis of this condition; thus, drugs with sympathetic effect could precipitate TTC. This review outlines previous reports regarding drugs that may induce TTC. Some reports link the use of the drug-primarily associated with sympathetic overstimulation-with the development of TTC Consequently, drug-induced TTC should be considered in patients diagnosed with TTC.