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Journal: Current clinical pharmacology


The number of patients with end stage liver disease is growing worldwide. This is likely a result of advances in medical science that have allowed these patients to lead longer lives since the incidence of diseases such as alcoholic cirrhosis and viral hepatitis have remained stable or even decreased in recent years, at least in more developed nations. Many of these patients will require anesthetic care at some point. The understanding and application of basic principles of pharmacokinetics is paramount to the practice of anesthesia. An understanding of pharmacokinetic principles provides the anesthesiologist with a scientific foundation for achieving therapeutic objectives associated with the use of any drug; however, pathologic conditions often alter the expected kinetic profile of many drugs. This is particularly true in the anesthetic management of the patient with hepatic pathology as the liver plays a central role in the absorption, distribution, and elimination kinetics of most drugs and many active and inactive drug metabolites. We review normal liver physiology, pathophysiology of liver disease in general, and how liver failure affects the pharmacokinetics and pharmacodynamics of anesthetic agents; providing some specific examples.

Concepts: Pharmacology, Medicine, Cirrhosis, Liver, Illness, Anesthesia, Pharmacokinetics, Hepatic encephalopathy


The current study investigates the cytotoxicity mechanism of common drugs with piperazine ring such as cetirizine, olanzapine and buspirone on human lymphocytes. The viability of lymphocytes, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, lysosomal integrity, content of glutathione and lipid peroxidation were determined. Buspirone and cetirizine showed more toxicity than olanzapine on human lymphocytes with an IC50 value of 200 μg/ml, after 6 h of incubation. Significant ROS formation, MMP collapse, lipid peroxidation, lysosomal damage and elevation of glutathione disulfide (GSSG) were observed in treated lymphocytes concentrations (4, 20, 40 µg/ml) of buspirone and cetirizine. Our results show exposure of human lymphocytes with buspirone and cetirizine, which usually happens during the poisoning, triggers oxidative stress and organelle damages. Our study suggests that using antioxidants, mitochondrial and lysosomal protective agents can protect blood lymphocytes, from probable side effects of these highly consumed medications.


Melatonin is an endogenous neurohormone produced predominantly in the pineal gland. Recent studies have implicated abnormalities in melatonin physiology and the circadian rhythm in individuals with autism spectrum disorders (ASD). These physiological abnormalities include lower nighttime melatonin or melatonin metabolite concentrations in ASD compared to controls. These abnormalities in melatonin concentrations may be directly attributed to variations in melatonin pathway physiology as both functional and genetic variations in this pathway have been reported in children with ASD. Four studies have observed a correlation between abnormal melatonin concentrations and the severity of autistic behaviors. Twenty clinical studies have reported improvements in sleep parameters with exogenous melatonin supplementation in ASD, including longer sleep duration, less nighttime awakenings and quicker sleep onset. A recent meta-analysis of five randomized, double-blind, placebo-controlled crossover trials examining exogenous melatonin supplementation in ASD reported significant improvements with large effect sizes in total sleep duration and sleep onset latency compared to both baseline and placebo. Six studies reported that the nighttime administration of exogenous melatonin was associated with better daytime behaviors. Four studies reported improvements with exogenous melatonin supplementation when other sleep medications had previously failed. Adverse effects of melatonin were minimal to none in the twenty treatment studies. These studies indicate that the administration of exogenous melatonin for abnormal sleep parameters in ASD is evidence-based. Further studies examining optimal effective dosing and timing of dosing are warranted.

Concepts: Sleep, Autism, Pineal gland, Asperger syndrome, Autism spectrum, PDD-NOS, Circadian rhythm, Melatonin


Psoriasis is a common skin disorder characterized by hyper proliferation of keratinocytes. Although the exact pathophysiology of psoriasis is not entirely understood, immune system and its interaction with nervous system has been postulated and investigated as the underlying mechanism. The interaction between these two systems through cholinergic anti-inflammatory pathway and also endocannabinoid system, may suggest cannabinoids as potential addition to anti-psoriatic armamentarium.

Concepts: Immune system, Nervous system, Neurotransmitter, Dopamine, Parasympathetic nervous system, Cannabinoid


Opioid analgesics used to treat pain can cause respiratory depression. However, this effect has not been extensively studied, and life- threatening, opioid-induced respiratory depression remains difficult to predict. We tested the ventilatory response to hypercapnia for evaluating the pharmacodynamic effect of a drug on respiratory depression.


The use of levetiracetam (LEV) has been increasing given its favorable pharmacokinetic profile. Numerous population pharmacokinetic studies for LEV have been conducted. However, there are some discrepancies regarding factors affecting its pharmacokinetic variability. Therefore, this systematic review aimed to summarize significant predictors for LEV pharmacokinetics as well as the need for dosage adjustments.


Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion from the innovator to generic formulation, high-quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients.


Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs including neuraminidase inhibitors (NIs). However, information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify drugs associated with abnormal behavior using a spontaneous reporting system database.


Coronary artery disease is a major cause of morbidity and mortality worldwide. A major health concern in developing countries is opioid addiction, which has controversial cardiovascular side effects. We aimed to investigate whether myocardial infarction (MI) and its risk factors are associated with morphine dependency in the Iranian population.


Our study aims at assessing the pre-clinical impact of the synergistic mechanism of Daptomycin (DAP) and Ceftaroline (CFT) in patients with Methicillin-resistant Staphylococcus aureus bacteremia infections (MRSAB).