Recreational drug toxicity with severe hyperthermia: Rapid onsite treatment and clinical course.

Electronic dance music festivals have gained notoriety in the critical care and emergency medicine fields due to an alarming incidence of hospitalizations and deaths related to the high prevalence of recreational drug use. Recreational drug use toxicity, in part related to sympathomimetic toxidromes, may cause hyponatremia, seizures, rhabdomyolysis, hyperkalemia, acidosis, coagulopathy, circulatory shock, multi-organ failure, and even death. This wide-ranging syndrome has been referred to as psychostimulant drug-induced toxicity. Rapid onsite diagnosis and treatment, with attention to the A-B-C's of clinical emergencies, is essential to preserve life. We describe a patient presenting with the highest recorded core temperature in a survivor of psychostimulant drug-induced toxicity, and emphasize management principles of this life-threatening and increasingly prevalent condition.

Sympathomimetics regulate quantal acetylcholine release at neuromuscular junctions through various types of adrenoreceptors.

The studies of the interaction between the sympathetic and motor nervous systems are extremely relevant due to therapy for many neurodegenerative and cardiovascular disorders involving adrenergic compounds. Evidences indicate close contact between sympathetic varicosities and neuromuscular synapses. This raises questions about the effects of catecholamines on synaptic transmission. The currently available information is contradictory, and the types of adrenoreceptors responsible for modulation of neurotransmitter release have not been identified in mammalian neuromuscular synapses. Our results have shown that the α1A, α1B, α2A, α2B, α2C, and ß1 adrenoreceptor subtypes are expressed in mouse diaphragm muscle containing neuromuscular synapses and sympathetic varicosities. Pharmacological stimulation of adrenoreceptors affects both spontaneous and evoked acetylcholine quantal secretion. Agonists of the α1, α2 and ß1 adrenoreceptors decrease spontaneous release. Activation of the α2 and ß1 adrenoreceptors reduces the number of acetylcholine quanta released in response to a nerve stimulus (quantal content), but an agonist of the ß2 receptors increases quantal content. Activation of α2 and ß2 adrenoreceptors alters the kinetics of acetylcholine quantal release by desynchronizing the neurosecretory process. Specific blockers of these receptors eliminate the effects of the specific agonists. The action of blockers on quantal acetylcholine secretion indicates possible action of endogenous catecholamines on neuromuscular transmission. Elucidating the molecular mechanisms by which clinically utilized adrenomimetics and adrenoblockers regulate synaptic vesicle release at the motor axon terminal will lead to the creation of improved and safer sympathomimetics for the treatment of various neurodegenerative diseases with synaptic defects.

Treatment of intraoperative hypotension with cafedrine/theodrenaline versus ephedrine : A prospective, national, multicenter, non-interventional study-the HYPOTENS trial.

BACKGROUND: Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally. METHODS: HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures. RESULTS: A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E. CONCLUSION: Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.

Sympathomimetics regulate neuromuscular junction transmission through TRPV1, P/Q- and N-type Ca2+ channels.

Increasing evidence indicates that, first, the sympathetic nervous system interacts extensively with both vasculature and skeletal muscle fibers near neuromuscular junctions (NMJs) and, second, its neurotransmitter, noradrenaline, influences myofiber molecular composition and function and motor innervation. Since sympathomimetic agents have been reported to improve NMJ transmission, we examined whether two in clinical use, salbutamol and clenbuterol, affect the motor axon terminal via extracellular Ca2+ and molecular targets, such as TRPV1 and P/Q- and N-type voltage-activated Ca2+ channels. Electrophysiological recordings in ex-vivo preparations of peroneal nerves and lumbricalis muscles from young adult mice focused on spontaneous miniature end-plate potentials and singly and repetitively evoked end-plate potentials. Adding one dose of salbutamol or clenbuterol to the nerve/muscle preparation or repeatedly administering salbutamol to a mouse for 4 weeks increased spontaneous and evoked synaptic vesicle release but induced a steep decline in EPP amplitude in response to repetitive nerve stimulation. These effects were mediated primarily by ω-agatoxin IVA-sensitive P/Q-type and secondarily by ω-conotoxin GVIA-sensitive N-type Ca2+ channels. Presynaptic arvanil-sensitive TRPV1 channels seem to regulate Ca2+ at the motor neuron terminal at rest, while putative presynaptic ß-adrenergic receptors may mediate sympathomimetic and catecholamine effects on presynaptic Ca2+ channels during NMJ activation.

Antenatal exposure to fenoterol is not associated with the development of retinopathy of prematurity in infants born before 32 weeks of gestation.

PURPOSE: Despite safety concerns, ß2-sympathomimetics are still widely used as tocolytic agents. ß-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the ß2-sympathomimetic fenoterol contributes to the development of ROP. METHODS: For this single-center retrospective case-control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. RESULTS: n = 1134 infants < 32 weeks of gestation were screened for eligibility, out of which n = 722 met the inclusion criteria. Exposure to fenoterol (n = 505) was not associated with a higher rate of ROP (OR 0.721, 95% CI 0.463-1.122). Further, duration of exposure (days) did not alter the incidence of ROP (OR 1.001, 95% CI 0.986-1.016). Frequency distribution of different ROP stages and the need for therapeutic intervention was also not affected by prenatal exposure to fenoterol. Risk factors for the development of ROP like low birth weight, low gestational age, prolonged respiratory support and multiple gestation were confirmed in our large study cohort. CONCLUSION: ß2-Sympathomimetic tocolysis does not increase the rate of ROP in premature infants born < 32 weeks of gestation. Our results render fenoterol a safe tocolytic agent regarding neonatal ROP development.

Brain Computed Tomography in Stimulant Poisoning with Altered Consciousness.

BACKGROUND: Stimulant poisoning frequently causes altered mental status (AMS) and can result in severe cerebral vascular complications. The role of noncontrast brain computed tomography (CT) in acute stimulant-poisoned patients presenting with AMS remains unclear. OBJECTIVES: We examined the results and impacts of brain CT in acute stimulant-poisoned patients with AMS. METHODS: We performed a retrospective single-center study that included all adult patients who presented to the emergency department with stimulant poisoning and AMS (Glasgow coma scale [GCS] score <15) between January 1, 2010 and December 31, 2017. Patients who had concomitant head trauma or who presented with focal neurologic symptoms were excluded. The primary outcome was the rate of acute abnormalities on brain CT. The secondary outcomes were to identify factors that affected the decision to perform brain CT in stimulant-poisoned patients with AMS and whether obtaining the brain CT scan itself affected the patients' prognoses. RESULTS: The analysis included 66 patients, of whom 6 died from the poisoning. Noncontrast brain CT was performed in 31 patients and none had acute abnormalities. Patients who underwent brain CT were found to have worse GCS scores, higher body temperatures, higher intubation rates, higher admission rates, longer admission periods and intensive care unit stays, and a higher mortality rate. After adjusting for the propensity score, performing brain CT itself did not independently affect the patients' clinical outcomes. CONCLUSIONS: Nontrauma stimulant-poisoned patients presenting with AMS and without focal neurologic symptoms were unlikely to have acute abnormalities on brain CT. Patients who underwent brain CT scans had worse consciousness and greater disease severity.

Cardiovascular effects of increasing dosages of norepinephrine in healthy isoflurane-anesthetized New Zealand White rabbits.

OBJECTIVE: To characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation). METHODS: Rabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg-1) and midazolam (0.5 mg kg-1). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 µg kg-1 minute-1; medium, 0.5 µg kg-1 minute-1; and high doses, 1 µg kg-1 minute-1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey's post hoc comparison was performed (p < 0.05). RESULTS: Significant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments. CONCLUSIONS AND CLINICAL RELEVANCE: The infusion of NE at 0.5-1.0 µg kg-1 minute-1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits.

Tocolysis with the ß2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants.

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.

Efficacy and Outcomes After Vasopressin Guideline Implementation in Septic Shock.

BACKGROUND: In septic shock, the dose of norepinephrine (NE) at which vasopressin (AVP) should be added is unknown. Following an increase in AVP price, our medical intensive care unit (MICU) revised its vasopressor guidelines to reserve AVP for patients requiring greater than 50 µg/min of NE. OBJECTIVE: The purpose of this study is to compare efficacy and safety outcomes for patients admitted before the guideline revision with those for patients admitted after the revision. METHODS: This was a single-center, retrospective cohort study of patients admitted to Vanderbilt University Medical Center from November 1, 2014, to November 30, 2015. Before June 1, 2015, the vasopressor guidelines recommended initiation of AVP for patients requiring 10 µg/min of NE or greater. After June 1, 2015, the guidelines recommended initiation of AVP at a NE dose of 50 µg/min or greater. RESULTS: Time to achieve goal mean arterial pressure (MAP) was shorter in the postintervention group (2.0 vs 1.3 hours; P = 0.03) in univariate analysis but not after adjusting for prespecified confounders. Incidence of new arrhythmias was similar between the 2 groups (14.9% vs 10.9%; P = 0.567). In multivariable analysis accounting for baseline severity of illness, admission after the revision was associated with decreased 28-day mortality (odds ratio = 0.34; 95% CI = 0.16-0.71; P = 0.004). CONCLUSIONS: Use of a vasopressor guideline restricting AVP initiation in septic patients to those on at least 50 µg/min of NE appeared to be safe and did not affect the time to reach goal MAP.

Beta2-adrenergic stimulation increases energy expenditure at rest, but not during submaximal exercise in active overweight men.

PURPOSE: ß2-Agonists have been proposed as weight-loss treatment, because they elevate energy expenditure. However, it is unknown what effect ß2-agonists have on energy expenditure in overweight individuals. Furthermore, the influence of ß2-agonist R- and S-enantiomer ratio for the increased energy expenditure is insufficiently explored. METHODS: Nineteen males were included in the study of which 14 completed. Subjects were 31.6 (±3.5) years [mean (±95% CI)] and had a fat percentage of 22.7 (±2.1)%. On separate days, subjects received either placebo or inhaled racemic (rac-) formoterol (2 × 27 µg). After an overnight fast, energy expenditure and substrate oxidation were estimated by indirect calorimetry at rest and during submaximal exercise. Plasma (R,R)- and (S,S)-formoterol enantiomer levels were measured by ultra-performance liquid chromatograph-mass spectrometry. RESULTS: At rest, energy expenditure and fat oxidation were 12% (P ≤ 0.001) and 38% (P = 0.006) higher for rac-formoterol than placebo. Systemic (R,R):(S,S) formoterol ratio was correlated with change in energy expenditure at rest in response to rac-formoterol (r = 0.63, P = 0.028), whereas no association was observed between fat percentage and rac-formoterol-induced change in energy expenditure. During exercise, energy expenditure was not different between treatments, although carbohydrate oxidation was 15% higher (P = 0.021) for rac-formoterol than placebo. Rac-formoterol-induced shift in substrate choice from rest to exercise was related to plasma ln-rac-formoterol concentrations (r = 0.75, P = 0.005). CONCLUSION: Selective ß2-adrenoceptor agonism effectively increases metabolic rate and fat oxidation in overweight individuals. The potential for weight loss induced by ß2-agonists may be greater for R-enantiopure formulations.

Effects of different mydriatics on intraocular pressure, pupil diameter, and ruminal and intestinal motility in healthy sheep.

OBJECTIVE: To determine the effects of the administration of subconjunctival 1% atropine (SA), topical 1% atropine (A), 0.5% tropicamide (T), 1% homatropine (H), 10% phenylephrine (P), and 2% ibopamine (I) on intraocular pressure (IOP), pupil diameter (PD), ruminal motility (RM) and intestinal motility (IM) in sheep. ANIMAL STUDIED: Ten spayed ewes of Santa Inês breed. PROCEDURES: Six experiments were performed separately at 1-week intervals. One eye was randomly selected and received one drop of A, T, H, P, I, or subconjunctival injection of atropine at 8 a.m. On the following days, IOP and PD were evaluated every 8 h until the pupil returned to its normal diameter. Ruminal motility and intestinal motility were evaluated only within the first 13 h. RESULTS: The IOP did not change significantly in the treated eyes compared with the control eyes and baseline at any time point (P > 0.05). A longer-lasting pupil dilation was observed after the administration of A (96 h), SA (79 h), H (24 h), and T (24 h). Within the first 30 min after treatment, RM and IM decreased, by 78% and 82% (H), 76% and 86% (SA), 46% and 58% (A), and 62% and 70% (T) (P < 0.001), respectively, with a tendency to return to baseline values following 13 h of drug administration. Both 10% phenylephrine and 2% ibopamine did not have any effect on the parameters evaluated (P > 0.05). CONCLUSIONS: Topical and subconjunctival 1% atropine, 0.5% tropicamide, and 1% homatropine significantly reduced RM and IM, and induced pupil dilation but did not change IOP in eyes of healthy sheep. The sympathomimetics phenylephrine (10%) and ibopamine (2%) did not change the parameters evaluated.

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.

Neurologic Deficits Following Oral Misuse of the Nasal Decongestant Propylhexedrine.

INTRODUCTION: Propylhexedrine is an over-the-counter nasal decongestant used recreationally for amphetamine-like effects. Prior reports have associated intravenous misuse with brainstem dysfunction and diplopia. This is a case of propylhexedrine ingestion resulting in neurological impairment with associated MRI findings. CASE REPORT: A 21-year-old man presented with neurologic symptoms after ingesting propylhexedrine extracted from a 250 mg nasal inhaler into a lemon juice solution following recommendations from an online forum. He also followed recommendations to simultaneously ingest 1 g L-arginine to theoretically mitigate the risk of vasoconstriction. He developed flushing and euphoria before falling asleep. He awoke 12 h later with dizziness, intractable vomiting, diplopia, ataxia, dysmetria, and spontaneous horizontal nystagmus. Magnetic resonance imaging (MRI) revealed T2 enhancement concerning for vasogenic edema of the right posterior limbs of the internal capsule extending into the midbrain, cerebellar peduncles, and cerebellar white matter. Workup for primary vascular or autoimmune etiologies was unrevealing. Expanded drug testing was positive for mitragynine and THC. Blood analyzed via liquid chromatography quadrupole time-of-flight mass spectrometry was positive for propylhexedrine. On hospital day 6, the patient was discharged to physical rehabilitation with unresolved dysmetria and ataxia. DISCUSSION: Recreational oral misuse of propylhexedrine may be associated with neurologic injury. MRI findings in this case demonstrated vasogenic edema suggesting vasospasm as a possible etiology. Serum testing confirmed the presence of propylhexedrine. Although testing was also positive for mitragynine and THC, these have not been associated with similar neurologic deficits or MRI findings.

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

Central serous chorioretinopathy associated with Adderall (dextroamphetamine-amphetamine) and topical steroid use.

Purpose: To report a case of central serous chorioretinopathy (CSC) associated with Adderall (dextroamphetamine-amphetamine) and topical steroid use. Observations: A 34-year-old man presented for evaluation of a "cloud" in his vision for three months. He was taking Adderall for attention deficit hyperactivity disorder and mometasone 0.1% topical cream for eczema. He was found to have subretinal fluid in the left eye consistent with CSC. The subretinal fluid persisted despite cessation of the steroid cream but resolved after cessation of the Adderall. The subretinal fluid returned when the patient restarted Adderall and again resolved after he stopped it for a second time. Conclusions: Though we cannot prove causality, the course of events was suggestive of a direct relationship between Adderall use and CSC in this patient, with exogenous steroid as a possible modifying factor.

An overview of emergency pharmacotherapy for priapism.

INTRODUCTION: Priapism is a compartment syndrome, defined as an unwanted penile erection lasting longer than 4 h, unrelated to sexual stimulation, and persistent even after ejaculation/orgasm. Ischemic priapism is considered a urologic emergency requiring time-sensitive management. Studies have documented that untreated priapism is associated with progressive ischemic histological changes in the corpora cavernosa, such as widespread smooth muscle necrosis, blood vessel and nerve attrition, and trabecular fibrosis. Treatment options include conservative management, corporal irrigation, pharmacologic therapy, and surgery. We herein provide an overview of the emergency pharmacology for priapism. AREAS COVERED: The American Urological Association (AUA) and the European Association of Urology (EAU) both recommend penile aspiration in conjunction with intracavernosal injection of sympathomimetics as the initial management of ischemic priapism. We have performed a retrospective review of the literature from 1914 to 2022 by using PubMed and a review of the treatment guidelines from the AUA and the EAU to discuss the various therapies for ischemic priapism in the emergent setting. EXPERT OPINION: After a thorough overview of the literature regarding the treatment of ischemic priapism in the emergent setting, we conclude that intracavernosal phenylephrine is superior to other agents due to its demonstrated efficacy and limited systemic side effects.

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern.

Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or 'crack' cocaine, the free base. While the first is commonly administered by insufflation ('snorting') or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine's prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

A novel DOK7 mutation causing congenital myasthenic syndrome with limb-girdle weakness: case series of three family members.

Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation.

Sympathomimetics in veterinary species under anesthesia.

Sympathomimetic drugs mimic the physiological action of the sympathetic nervous system through interaction with adrenergic receptors. These drugs are commonly used to provide cardiovascular support in many veterinary species. Despite their common use, the literature evaluating their effectiveness can be somewhat limited depending on the species. This review details the mechanism of action of various sympathomimetic drugs and summarizes the literature that is available describing the efficacy of these drugs and their use in anesthetized veterinary species.