Undesirable Side Effects Of Drugs Research Articles

Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms.

Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations in organ structure, biomechanical properties, and function. Indeed, fibrosis is now appreciated to be an important cause of mortality and morbidity. Extensive research has illustrated that fibrosis can be slowed, arrested or even reversed; however, few drugs have been approved specifically for anti-fibrotic treatment. This is in part due to the complex pathways responsible for fibrogenesis and the undesirable side effects of drugs targeting these pathways. Natural products have been utilized for thousands of years as a major component of traditional medicine and currently account for almost one-third of drugs used clinically worldwide. A variety of plant-derived compounds have been demonstrated to have preventative or even reversal effects on fibrosis. This review will discuss the effects and the underlying mechanisms of some of the major plant-derived compounds that have been identified to impact fibrosis.

Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues.

Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, their cell-like membrane organization facilitates uptake and accumulation in specific tissues and organs, which can be exploited to improve selectivity of cargo delivery. The combination of these properties with the inclusion of drugs or imaging agents can significantly improve therapeutic efficacy and selectivity, reduce the undesirable side effects of drugs or permit earlier diagnosis of diseases. In this review, we will describe the natural properties of EVs isolated from different cell sources and discuss strategies that can be applied to increase the efficacy of targeting drugs or other contents to specific locations. The potential risks associated with the use of EVs will also be addressed.

Comparative effect of intravenous nalbuphine versus intravenous paracetamol for post-operative obstetric analgesia

Background: Management of the post-operative pain after cesarean section (CS) requires a balance between the pain relief and undesirable side effects of drugs. To improve the post-operative pain management after CS, we compared analgesic efficacy of i.v nalbuphine versus i.v paracetamol for post-operative CS pain. Aim and Objective: The aim of the study was to compare the efficacy and safety of single-dose intravenous nalbuphine versus intravenous paracetamol for post-operative analgesia CS pain. Materials and Methods: This was a hospital-based retrospective study in the department of obstetrics, gynecology, among 120 patients of CS. We enrolled 120 patients in our prospective randomized trial after an uneventful elective CS under the spinal anesthesia. Group A patients received i.v paracetamol infusion and Group B patients received i.v nalbuphine on the first complaint of pain. The results were analyzed byt-test; P

Addressing Solubility through Nano Based Drug Delivery Systems

Developing new techniques to overcome poor solubility in drug development remains a challenge for the pharmaceutical industry. It is estimated that up to 40% of newly discovered chemical entities are insoluble. This has led industry to turn to new approaches such as nanotechnology to help overcome solubility. Nanotechnology based drug delivery systems have been associated with improving therapeutic activity and minimising undesirable side effects of drugs. Nanotechnology is an emerging field that has the potential to change the way illnesses are treated and drugs delivered. Despite enthusiasm amongst formulation researchers that nanotechnology could be the answer to improving solubility and deliverability of drugs, concerns regarding toxicology and long term effects of nanomaterial on the body need to be investigated further. This review describes advance drug delivery systems such as liposomes, dendrimers and polymeric micelles which have been explored as drug delivery vehicles and provides an overview of each system.

Postoperative Analgesia Following Caesarean Section: Intravenous Patient Controlled Analgesia Versus Conventional Continuous Infusion

Background: Management of postoperative pain after caesarean section (C/S) requires a balance between pain relief and undesirable side effects of drugs and technique. In order to improve postoperative pain management after caesarean section, we compared intravenous patient controlled analgesia (IV-PCA) with our current hospital practice, which is continuous opioid infusion. Method: We enrolled one hundred and twenty patients in our prospective randomized trial after an uneventful elective caesarean section under spinal anaesthesia. All patients received 0.5 mg/kg bolus of pethidine on first complaint of pain or at 120 minutes after institution of spinal anaesthesia. Depending upon the randomization, Group P received IV-PCA with 0.15 mg/kg bolus pethidine with 10-minute lockout and Group C received continuous pethidine infusion at a rate of 0.15 mg/kg/hr. Statistical analysis: For qualitative variables means and standard deviations were computed and analyzed by T-test, Mann Whitney U test and repeated measures ANOVA. Frequency and percentages were computed for qualitative data and analyzed by Chi-Square and Fischer exact test. A p-value of less than 0.05 was treated as significant. Results: The numeric rating score for pain, need for rescue analgesia and incidence of nausea and vomiting was significantly lower (p-value < 0.001) in IV-PCA group as compared to continuous infusion group at 6, 12 and 24 hours postoperatively, 98% of the patients were satisfied with pain management in Group P as compared to 70% (p < 0.001) in Group C. Conclusion: Our results showed improved pain control, less need for rescue analgesia for breakthrough pain, lower incidence of nausea and vomiting and greater patient satisfaction with IV-PCA. In the absence of preservative free narcotics for intrathecal use, postoperative pain management can be significantly improved by using IV-PCA instead of continuous opioid infusion in patients undergoing caesarean section.

Arzneimittelinteraktionen in der Urologie

Many patients concomitantly receive multiple urological and nonurological medications. This practice can lead to drug-drug interactions (DDIs). These interactions can be pharmacodynamic (acting on the same body function) or pharmacokinetic (affecting each other's concentrations) and are a frequent cause of adverse drug reactions. Examples of pharmacodynamic DDIs include the use of overactive bladder drugs together with those prescribed for psychiatric or neurological indications that also have anticholinergic properties, or the use of PDE5 inhibitors together with vasodilating drugs, particularly nitrates. Pharmacokinetic DDIs are mainly due to effects on drug metabolism, specifically that involving CYP3A4 and 2D6, or on drug transporters. Drugs can both inhibit and induce the activity of many of these enzymes and transporters. CYP3A4 inducers can lower levels of cyclosporine or tacrolimus so much that transplant rejection occurs, and CYP3A4 inhibitors can increase their levels, leading to nephrotoxicity. Levels of the anticholinergic darifenacin can be increased so much by potent CYP3A4 inhibitors that this combination is contraindicated. These examples show that knowledge of DDI can help patients avoid undesirable side effects of drugs.

Health-related Interactions of Phytochemicals

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Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers.

In this paper, we present a pharmacophore for QT-prolonging drugs, along with a 3D QSAR (CoMFA) study for a series of very structurally variegate HERG K(+) channel blockers. The blockade of HERG K(+) channels is one of the most important molecular mechanisms through which QT-prolonging drugs increase cardiac action potential duration. Since QT prolongation is one of the most undesirable side effects of drugs, we first tried to identify the minimum set of molecular features responsible for this action and then we attempted to develop a quantitative model correlating the 3D stereoelectronic characteristics of the molecules with their HERG blocking potency. Having considered an initial set of 31 QT-prolonging drugs for which the HERG K(+) channel blocking activity was measured on mammalian transfected cells, we started the construction of a theoretical screening tool able to predict whether a new molecule can interact with the HERG channel and eventually induce the long QT syndrome. This in silico tool might be useful in the design of new drug candidates devoid of the physicochemical features likely to cause the above-mentioned side effect.

Recent advances in ocular cataract research

Cataracts account for blindness in 17 million people worldwide. Prevention and treatment of opacity of the lens requires complete understanding of lens biochemistry and structure. Anthony Cerami and James Crabbe discuss the evidence for the various mechanisms of cataract formation that have been proposed, based on results from experimental animals. For pharmacologists there are two implications: firstly, cataracts can result as undesirable side-effects of drugs; and secondly, there is now potential for the rational development of drugs which interfere with cataract formation. Inhibitors of aldose reductase are already available.