A Case of High Dose Metoprolol Poisoning; Case Report and Literature Review

β-Blockers are prescribed by physicians for many medical reasons (hypertension, long-term prophylaxis of angina pectoris, myocardial infarction, stable heart failure treatment, cardiac arrhythmias, etc.). Although cases of β-blocker poisoning have a low rate of 0.9% among all poisoning cases, they have a high mortality rate. In β-blocker poisoning with high lipid solubility; seizures, respiratory depression, coma, resistant bradycardia-hypotension and shock may occur. Metoprolol, a type of β-blocker, is a selective β1-adrenoceptor antagonist with sympathomimetic effect. It is also reported that metoprolol is the 2nd most commonly prescribed β-blocker after bisoprolol all over the world. This article aims to present a case who took high-dose metoprolol for suicidal purposes and to examine metoprolol poisoning and its treatment in the light of current literature.

β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study

Aim: To compare different β-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

Inhalant Abuse of Ethyl Chloride Spray: A Case Report

Ethyl chloride spray, which is usually used to relieve pain after injuries, is increasingly being used as a sniffing alternative. The number of people using this is rising due to its easy availability, cost-effectiveness and legality. The high lipid solubility of ethyl chloride leads to a rapid absorption of it in the lungs. However, data on the biotransformation of ethyl chloride in humans are sparse. We present the case of a 53-year-old male who had been inhaling ethyl chloride up to 3 times a week since 25 years, and describe his symptoms and the circumstances of abuse. This should help raise awareness of this issue so that abuse can be recognized early and rapid action taken.

Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine’s potential in the treatment or prevention of obesity complications.

Benzodiazepine Intoxication in a Neonate by Maternal Use in Pregnancy

The abuse of benzodiazepines by pregnant women can cause intoxication in the neonate. Benzodiazepines can diffuse readily across the placenta to the fetus because of their high lipid solubility. After the sixth month of pregnancy, the loss of the cytotrophoblasts from the placenta further facilitates the transport of benzodiazepines across the placenta. They may persist for at least a week in pharmacologically active concentrations after administration of high dosages to the mother. We report about a floppy, drowsy and pulmonary impaired newborn delivered in the 36th week of gestation. The mother was a regular user of clorazepate, a long-acting benzodiazepine during pregnancy.

Organochlorine Pesticides

Indiscriminate use of different pesticides in agriculture has increased over the years, especially in the developing countries. This influences the aquatic environment to a great extent. This also poses a great danger to freshwater organisms, including fish, which constitute a major share in the aquatic environment and contribute to the economy of the nation. Water pollution is posing intricate problems that need immediate redress. Organo-chlorine pesticides (OCPs) are a major contributor to aquatic pollution and are amongst the most serious global contaminants. In addition, organochlorine pesticides have a tendency to accumulate in aquatic biota; they also undergo food chain amplification. Lipophilic pollutants are chemically very stable and resistant to microbial, photochemical, chemical, and thermal degradation. The chemical stability of these compounds, their high lipid solubility, and their toxicity to human beings and animals has led government and researchers to feel concerned about their presence in the environment.

Inflammation as a target of minocycline: special interest in the regulation of inflammasome signaling

Minocycline is a wide-spectrum antibiotic derived from tetracycline. In addition to its anti-microbial activity, minocycline is known to possess several immunomodulatory and neuroprotective properties. Fewer severe side effects and more efficient tissue penetration make minocycline better than its parent tetracycline. Doxycycline competes with minocycline in improved biological half-life but minocycline becomes more rapidly absorbed in tissues than doxycycline. Due to its high lipid solubility, minocycline also crosses the blood-brain barrier easily, which increases its relevance in the treatment of diseases beyond the barriers. Inflammasomes are intracellular protein complexes which become primed via NF-kB and MAPK pathways, and activated by various PAMPs and DAMPs. In this article, we hypothese about the capability of minocycline to regulate inflammasomes as part of its anti-inflammatory activity. The hypothesis is based on the ability of minocycline to regulate signals essential to both the priming and the activation of inflammasome signaling

Comparison of Intracarotid and Intravenous Propofol for Electrocerebral Silence in Rabbits

Background The high lipid solubility that permits rapid transfer across the blood-brain barrier makes propofol attractive for intracarotid injection. The authors hypothesized that intracarotid injection produces electrocerebral silence at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects. Methods The authors compared the systemic and cerebrovascular effects of intracarotid and intravenous propofol during transient (10 s) and sustained (1 h) electrocerebral silence in anesthetized New Zealand White rabbits. Hemispheric electrocerebral activity, mean arterial blood pressure, ipsilateral and contralateral cerebral blood flow, tympanic temperature, and end-tidal carbon dioxide were continuously monitored in these animals. Changes in outcome variables were analyzed at four time points: at baseline, during electrical silence, during burst suppression, and after recovery of electrocerebral activity. Propofol (1%) was injected as intracarotid (0.1 ml) or intravenous (0.5 ml) boluses. Results Intracarotid propofol produced electrocerebral silence at one fifth (sustained silence) to one tenth (transient silence) of the intravenous dose. Compared with baseline values, the mean arterial pressure and ipsilateral cerebral blood flow remained unchanged or decreased transiently during electrocerebral silence with intracarotid propofol. In contrast, intravenous propofol resulted in systemic hypotension and a decrease in ipsilateral cerebral blood flow. Conclusions Intracarotid propofol resulted in electrocerebral silence at a fraction of the intravenous dose that was not associated with systemic hypotension or a sustained decrease in the cerebral blood flow. Intracarotid propofol could be potentially useful for providing electrocerebral silence when cerebral perfusion is at risk.

Ketamine: In the past thirty years and in the future

Introduction There are two isomers of ketamine: S(+)ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-D-aspartate (NMDA), opioid and muscarinic receptors. Pharmacokinetics Due to its high lipid solubility and low protein binding, ketamine is extensively distributed in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. Effects on body systems Ketamine causes increased intracranial pressure, bronchodilation and stimulation of cardiovascular system. Clinical use Anesthesia It is used for premedication, sedation, induction and maintenance of general anesthesia. Ketamine is an ideal anesthetic agent for trauma victims, patients with hypovolemic and septic shock, patients with pulmonary diseases. Analgesia Even subanesthetic doses of ketamine have analgesic effects, so ketamine is also recommended for postoperative analgesia. Recent results show that ketamine is not always effective as an analgesic in treatment of chronic pain and that some side effects limit its use in patients with chronic pain. Intensive care Combination of ketamine and midazolam can be very useful and safe for sedation and pain relief in intensive care patients, especially during ventilator management. Ketamine may be the anesthetic of choice for painful procedures in intensive care units. Emergency medicine Ketamine is recommended for critically ill patients with sedative, inotropic and bronchodilatatory effects. New clinical use Future studies will reveal if ketamine can be used for outpatient anesthesia, intravenous regional anesthesia and in treatment of depression. S(+)ketamine is a more effective anesthetic with significantly less psychomotor effects which provides rapid recovery from anesthesia in regard to racemate or R(-)ketamine. Conclusion Increasing interest in use of ketamine has resulted from current knowledge. In the future we expect new clinical uses in treatment of acute and chronic pain, intensive care and emergency medicine.

Radioactively iodinated cyclo(His-Pro) crosses the blood-brain barrier and reverses ethanol-induced narcosis

Cyclo(His-Pro) (cHP) is a peptide widely distributed in the central nervous system (CNS) and peripheral tissues that can affect brain function after either peripheral or CNS administration. This suggests that cHP may be a neuromodulator capable of crossing the blood-brain barrier (BBB). We, therefore, studied the ability of radioactively labeled cHP (I-cHP) to cross the BBB. We found that I-cHP can cross the BBB in either the direction of blood to brain or brain to blood by nonsaturable mechanisms. The rate of entry of I-cHP into the CNS was low in comparison with other peptides, especially considering its relatively low molecular weight and high lipid solubility. However, this slow entry was offset by a long half-life in blood and extreme enzymatic resistance, allowing cHP to accumulate in the CNS. This accumulation was sufficient to allow intravenous cHP to reverse ethanol-induced narcosis, an effect mediated through the CNS. The rate of entry of I-cHP was resistant to conditions that alter the passage of some other substances across the BBB or that have been shown to affect cHP metabolism such as aging, diabetes, and pretreatment with aluminum. Entry of cHP into the brain was not retarded by binding to serum proteins. Significant amounts of I-cHP entered the serum, brain, and other tissues after intraperitoneal administration, the route used in many studies of cHP. Taken together, these results show that cHP is a highly stable peptide that, after intravenous injection, slowly enters the brain by a nonsaturable mechanism in amounts large enough to affect such aspects of the CNS as ethanol-induced narcosis.