Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Coronary artery disease is a major cause of morbidity and mortality worldwide. A major health concern in the 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.

Methods: Electronic databases, including PubMed, Medline, Scopus, SID, Element, and Magiran were searched to find published articles including the keywords morphine, coronary artery disease, hypertension, hyperlipidemia, and diabetes mellitus.

Results: Twelve studies involving 25,800 people were included in this systematic review and metaanalysis. Morphine dependency was significantly associated with MI with an adjusted odds ratio (AOR) of 2.28 (95%CI=1.26-4.11). It neither has significant associations with hypertension (AOR=0.952; 95%CI=0.696-1.301) nor diabetes (AOR=0.895; 95%CI=0.644-1.246). Morphine dependency also had no significant association with hyperlipidemia with a Crude Odds Ratio (COR) of 0.906 (95%CI=0.786-1.045).

Conclusion: Morphine dependency was significantly related to MI, but its risk factors were not significantly associated with morphine dependency. The increasing prevalence of opioid abuse in developing countries may be a reason for the growing incidence of MI in younger ages and individuals with no risk factors. Besides, physicians should consider the presence of impurities in morphine-based opioids and their possible effects on health.

Objective: The study was conducted to determine whether synthetic Disease-Modifying Anti Rheumatic Drugs (DMARDs) suppress the latency of Tuberculosis (TB) infection in Rheumatoid Arthritis (RA) patients along with other variables.

Methods: This was done through Tuberculin Skin Test (TST) using purified protein derivative (PPD) in a cohort of RA patients. The TST was taken positive when induration post-PPD injection was ≥ 5mm and negative or anergic when it was < 5mm. We included 100 patients (N = 100).

Results: The prevalence of positive TST was 36%, while 64% presented a negative result. Negative TST was significantly associated with steroid usage (39.4%, 95% CI: 28.4%-51.4%). Anergic (TST negative) and non-anergic (TST positive) patients were separated into groups, and a new analysis was conducted with elaboration on DMARDs used.

Conclusion: The use of steroids was associated with TST negativity, The same is not true with use of methotrexate or other DMARDs. Thus TST should be interpreted with caution, especially before starting biologicals.

Background: The cesarean section has shown an increasing trend within the past few years. The use of appropriate and effective anesthesia for the procedure is important, not only to reduce the incidence of maternal and fetal morbidities but also to reduce the incidence of intraoperative consciousness. The aim of this study is to evaluate the intraoperative and postoperative effects of adjuvant ketamine, when used in combination with general anesthesia.

Methods: The study was conducted on the patients referred to Asali hospital for the cesarean section. 100 patients were assigned into two groups. Patients in Group A received thiopental (4 mg / kg) as an anesthetic agent for the surgery, whereas those in group B received thiopental along with 0.5 mg/kg of intravenous ketamine. The effects of ketamine, such as depth of anesthesia, intraoperative and postoperative awareness, vomiting and hallucination were recorded in the questionnaire and data were statistically analyzed using SPSS v25.

Results: Of 100 patients in group A, 10 of them were not deeply unconscious. 40 patients in group A and 25 in group B had intraoperative awareness. Depth of anesthesia was significantly associated with the use of ketamine (p = 0.0017) 1 patient in group A and 3 in group B had vomiting and 1 patient in group B was presented with the hallucinations. These parameters were not significantly associated with the dose of ketamine (p = 0.5).

Conclusion: Overall use of ketamine is associated with better sedation and no significant side effects, with low doses of ketamine, were seen in our study. Comparative studies using other analgesics, with larger sample size, are therefore recommended.

Background: To address multidrug resistance, we developed engineered Cationic Antimicrobial Peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice, reducing bacterial loads to undetectable levels in diverse organs.

Objective: To support the development of WLBU2, we conducted a mass balance study.

Methods: CD1 mice were administered 10, 15, 20 and 30 mg/kg of QDx5 WLBU2 or a single dose of [14C]-WLBU2 at 15 mg/kg IV. Tolerability, tissue distribution and excretion were evaluated with liquid scintillation and HPLC-radiochromatography.

Results: The maximum tolerated dose of WLBU2 is 20 mg/kg IV. We could account for greater than >96% of the radioactivity distributed within mouse tissues at 5 and 15 min. By 24h, only ~40-50% of radioactivity remained in the mice. The greatest % of the dose was present in liver, accounting for ~35% of radioactivity at 5 and 15 min, and ~ 8% of radioactivity remained at 24h. High radioactivity was also present in kidneys, plasma, red blood cells and lungs, while less than 0.2% of radioactivity was present in brain, fat, or skeletal muscle. Urinary and fecal excretion accounted for 12.5 and 2.2% of radioactivity at 24h.

Conclusion: WLBU2 distributes widely to mouse tissues and is rapidly cleared with a terminal radioactivity half-life of 22 h, a clearance of 27.4 mL/h/kg, and a distribution volume of 0.94 L/kg. At 2-100 μg-eq/g, the concentrations of 14C-WLBU2 appear high enough in the tissues to account for the inhibition of microbial growth.

Background: Monogenic Diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people younger than 45 years old. Maturity-Onset Diabetes of the Young (MODY), neonatal diabetes, and several syndromic forms of diabetes are included among the most accounts for about typical forms of MDF. MODY is the most frequent type of MFD, with MODY 1, 2, 3, and 5 being the most prevalent forms. The aim of this narrative review is to describe pregnancy associated changes in the pharmacological profile of the antidiabetic drugs used in women with the most frequent MODY subtypes.

Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester.

Results: Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug.

Conclusion: The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.

Background: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia rats.

Methods: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose (9-81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27 mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time points post-dose, and hesperetin was determined by Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometric (UPLC-MS/MS).

Results: Compared with normal condition of group A, hyperuricemia of group C induced 48.19% and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic properties in the range of 9-81 mg/kg in hyperuricemia rats.

Conclusion: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28 days' treatment. These findings could provide more beneficial information to the mechanism and clinical applications of hesperetin.

Inflammatory Bowel Diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the '50s, are still the mainstay of treatment for moderate to severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on the long-term natural history of the disease, the steroid-sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so-called "low bioavailability" steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and a more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.

Background: Green tea has been extensively studied for its potential health benefits against diseases, such as cancers, cognitive degenerative diseases, and cardiovascular diseases.

Methods: The authors undertook a structured search of peer-reviewed research articles from three databases including PubMed, Embase, and Ovid MEDLINE. Recent and up-to-date studies relevant to the topic were included.

Results: Green tea extract exerts its functions by interacting with multiple signalling pathways in human cells. Protein tyrosine kinase is one of the examples. Abnormal activation of tyrosine kinase is observed in some tumour cells. Green tea extract inhibits phosphorylation, reduces expression, or attenuates downstream signalling of epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor, and non-receptor tyrosine kinase. Combination of green tea extract with tyrosine kinase inhibitors may provide synergistic effects by overcoming acquired resistance.

Conclusion: Green tea extract can affect multiple receptor targets. In the current review, we discuss the pharmacological mechanisms of green tea on tyrosine kinases and their implications on common diseases.

Background: Over the years, drug monitoring-such as Anti-Drug Antibodies (ADA) dosage- has witnessed major transformations. In fact, ADA are more and more used in rheumatology and gastro-enterology in monitoring chronic inflammatory disease therapeutic response. The main purpose of those researches is to produce less immunogenic drugs and, in consequences, to improve tolerance and efficiency since immunogenicity of those drugs still is the main constraint to their long-term use. The aim of this review was to highlight anti-drug-antibodies potential effects on the pharmacokinetics and bioavailability of biotherapies as well as their clinical implications.

Methods: For this purpose, we collected and summarized published data on PubMed using keywords "Biologics, Rheumatoid Arthritis, Spondyloarthritis, Crohn disease, Anti-drug antibodies, residual rate, immunogenicity, efficacy, tolerance". The time-period selected for this study was 2000-2019.

Results: Anti-Drug-antibodies decrease the pharmaco-availability of drugs and, in consequences, its efficiency and high risk of refractory diseases and side effects.

Conclusion: Recent literature is consistent with the fact that drug monitoring using ADA dosage coupled with residual drug concentration offers reliable options to comfort practitioner' therapeutic management decisions. This is particularly interesting in failure of treatment or in side effects onset situations.

Rationale & objective: Rodenticide poisoning, either accidental or intentional, is very common in rural India. The absence of a definite antidote made it a major concern with a high mortality rate. Therefore, this study aimed to assess the effectiveness of N-Acetyl Cysteine (NAC) in rodenticide poisoning as there are recent positive shreds of evidence on it.

Methodology: A retrospective study was conducted in a tertiary care teaching hospital on patients admitted with rodenticide poisoning during a period of 2012-2017. The Fischer's exact test and relative risk were measured to analyze the outcome of treatment and risk factors, respectively.

Results: A total of 229 patients were enrolled in the study with a mean age of 30.04 ± 15.67 years. The suicidal attack was the major (86.0%) reason for poison consumption. The survival rate was significantly (p ≤ 0.03) higher in the NAC treatment group compared to the non-NAC group. Moreover, the majority (93.4%) of participants did not experience any adverse effects. The mean oral loading dose and maintenance dose was 7580.95 ± 2204.29 mg and 3694.53 ± 2322.58 mg, respectively. Yellow Phosphorus poisoning (Relative Risk [RR] 2.888 (1.179-7.079); p=0.020) and Time lag of ≥ 24 hours (RR 3.479 (1.137-10.645); p=0.029) were the significant risk factors for mortality.

Conclusion: NAC is shown to have a significant survival benefit with a good safety profile among rodenticide poisoners. Further adequately powered prospective researches with more emphasis on dosing parameters are warranted for better quantification in different settings and for clinical implementation.