scholarly journals Non-Opioid Peptides Targeting Opioid Effects

2021 ◽  
Vol 22 (24) ◽  
pp. 13619
Author(s):  
Katarzyna Kaczyńska ◽  
Piotr Wojciechowski
Keyword(s):  
Side Effects ◽  
Respiratory Depression ◽  
Cardiovascular Events ◽  
Short Review ◽  
Opioid Activity ◽  
Inhibiting Factor ◽  
Neuropeptide Ff ◽  
Important Challenge ◽  
Related Compounds ◽  
Respiratory Responses

Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as tolerance, addiction, respiratory depression, and cardiovascular events. This, in turn, can result in their overuse in cases of addiction, the need for dose escalation in cases of developing tolerance, and the emergence of dose-related opioid toxicity, resulting in respiratory depression or cardiovascular problems that can even lead to unintentional death. Therefore, a very important challenge for researchers is to look for ways to counteract the side effects of opioids. The use of peptides and their related compounds, which have been shown to modulate the effects of opioids, may provide such an opportunity. This short review is a compendium of knowledge about the most important and recent findings regarding selected peptides and their modulatory effects on various opioid actions, including cardiovascular and respiratory responses. In addition to the peptides more commonly reported in the literature in the context of their pro- and/or anti-opioid activity—such as neuropeptide FF (NPFF), cholecystokinin (CCK), and melanocyte inhibiting factor (MIF)—we also included in the review nociceptin/orphanin (N/OFQ), ghrelin, oxytocin, endothelin, and venom peptides.

scholarly journals Pilot Study: Quantitative Photoacoustic Evaluation of Peripheral Vascular Dynamics Induced by Carfilzomib In Vivo

Sensors ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 836
Author(s):  
Thi Thao Mai ◽  
Manh-Cuong Vo ◽  
Tan-Huy Chu ◽  
Jin Young Kim ◽  
Chulhong Kim ◽  
...  
Keyword(s):  
Pilot Study ◽  
Side Effects ◽  
Cardiovascular Events ◽  
Evaluation Method ◽  
Vascular System ◽  
Maximum Amplitude ◽  
Peripheral Vascular ◽  
Peripheral Vasculature ◽  
Mouse Ear

Carfilzomib is mainly used to treat multiple myeloma. Several side effects have been reported in patients treated with carfilzomib, especially those associated with cardiovascular events, such as hypertension, congestive heart failure, and coronary artery disease. However, the side effects, especially the manifestation of cardiovascular events through capillaries, have not been fully investigated. Here, we performed a pilot experiment to monitor peripheral vascular dynamics in a mouse ear under the effects of carfilzomib using a quantitative photoacoustic vascular evaluation method. Before and after injecting the carfilzomib, bortezomib, and PBS solutions, we acquired high-resolution three-dimensional PAM data of the peripheral vasculature of the mouse ear during each experiment for 10 h. Then, the PAM maximum amplitude projection (MAP) images and five quantitative vascular parameters, i.e., photoacoustic (PA) signal, diameter, density, length fraction, and fractal dimension, were estimated. Quantitative results showed that carfilzomib induces a strong effect on the peripheral vascular system through a significant increase in all vascular parameters up to 50%, especially during the first 30 min after injection. Meanwhile, bortezomib and PBS do not have much impact on the peripheral vascular system. This pilot study verified PAM as a comprehensive method to investigate peripheral vasculature, along with the effects of carfilzomib. Therefore, we expect that PAM may be useful to predict cardiovascular events caused by carfilzomib.

Redefining residual inflammatory risk after acute coronary syndrome

2021 ◽  
Author(s):  
Marco G Del Buono ◽  
Rocco A Montone ◽  
Giulia Iannaccone ◽  
Riccardo Rinaldi ◽  
Giulia La Vecchia ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Multimodality Imaging ◽  
Short Review ◽  
Local Inflammation ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Atherosclerotic Plaque Formation ◽  
Long Term Follow Up ◽  
Coronary Syndromes

Over the last decades, inflammation proved to play a pivotal role in atherosclerotic plaque formation, progression and destabilization. Several studies showed that the patients presenting with acute coronary syndrome are at increased risk of adverse cardiovascular events at both short- and long-term follow-up. Results from different clinical trials highlighted that a residual inflammatory risk exist and targeting inflammation is a successful strategy in selected cases associated to an increased inflammatory burden. Recently, the optimization of intracoronary and multimodality imaging allowed to also assess the entity of local inflammation, thus encouraging the individuation of plaque characteristics that portend a higher risk of future cardiovascular events. In this short review, we aim to highlight the role of systemic and local inflammation in acute coronary syndromes, to provide a summarized overview of the possible medical strategies applicable in selected cases and to underline the diagnostic and prognostic potential of multimodality imaging.

scholarly journals Combination oral contraceptives – a practice-guided overview of everyday problems and their solutions

2020 ◽  
pp. 30-32
Author(s):  
DW Wolmarans ◽  
L Brand ◽  
SF Steyn
Keyword(s):  
Deep Vein Thrombosis ◽  
Side Effects ◽  
Adverse Effects ◽  
Oral Contraceptives ◽  
Cardiovascular Events ◽  
Treatment Withdrawal ◽  
Vein Thrombosis ◽  
Withdrawal Of Therapy ◽  
Deep Vein ◽  
Everyday Problems

Combination oral contraceptives (COCs) are some of the most commonly prescribed drugs for women between the ages of 15–451 and while they are accepted to be safe and highly effective, their use is often associated with a number of minor sideeffects. Considering the limited nature of this review, a detailed overview of the complete clinical profile of COCs falls beyond the current scope. Rather, we will focus on the most frequently reported side-effects of COCs that do not necessitate treatment withdrawal. Adverse effects that require immediate withdrawal of therapy are usually related to deep vein thrombosis (DVT) and other cardiovascular events, malignancies or hepatic pathology2 and would require a more in-depth review.

scholarly journals Modeling Polypharmacy Side Effects with Graph Convolutional Networks

2018 ◽  
Author(s):  
Marinka Zitnik ◽  
Monica Agrawal ◽  
Jure Leskovec
Keyword(s):  
Side Effects ◽  
Drug Interactions ◽  
Protein Interactions ◽  
Side Effect ◽  
Population Data ◽  
Model Parameters ◽  
Mortality And Morbidity ◽  
Convolutional Networks ◽  
Important Challenge ◽  
Complex Relationships

AbstractMotivation: The use of drug combinations, termed polypharmacy, is common to treat patients with complex diseases or co-existing conditions. However, a major consequence of polypharmacy is a much higher risk of adverse side effects for the patient. Polypharmacy side effects emerge because of drug-drug interactions, in which activity of one drug may change, favorably or unfavorably, if taken with another drug. The knowledge of drug interactions is often limited because these complex relationships are rare, and are usually not observed in relatively small clinical testing. Discovering polypharmacy side effects thus remains an important challenge with significant implications for patient mortality and morbidity.Results: Here, we present Decagon, an approach for modeling polypharmacy side effects. The approach constructs a multimodal graph of protein-protein interactions, drug-protein target interactions, and the polypharmacy side effects, which are represented as drug-drug interactions, where each side effect is an edge of a different type. Decagon is developed specifically to handle such multimodal graphs with a large number of edge types. Our approach develops a new graph convolutional neural network for multirelational link prediction in multimodal networks. Unlike approaches limited to predicting simple drug-drug interaction values, Decagon can predict the exact side effect, if any, through which a given drug combination manifests clinically. Decagon accurately predicts polypharmacy side effects, outperforming baselines by up to 69%. We find that it automatically learns representations of side effects indicative of co-occurrence of polypharmacy in patients. Furthermore, Decagon models particularly well polypharmacy side effects that have a strong molecular basis, while on predominantly non-molecular side effects, it achieves good performance because of effective sharing of model parameters across edge types. Decagon opens up opportunities to use large pharmacogenomic and patient population data to flag and prioritize polypharmacy side effects for follow-up analysis via formal pharmacological studies.Availability: Source code and preprocessed datasets are at: http://snap.stanford.edu/decagon.Contact:[email protected]

scholarly journals Clinical challenges in the management of endocrine side effects of immuno-oncological therapies

2021 ◽  
Author(s):  
Peter Wolf ◽  
Thomas Scherer
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Immune Checkpoint Inhibitor ◽  
Clinical Presentation ◽  
Checkpoint Inhibitor ◽  
Clinical Care ◽  
Short Review ◽  
Current Clinical Practice ◽  
Routine Clinical Care ◽  
Adequate Management

SummaryGiven the growing use of immune checkpoint inhibitor (ICI) therapy in oncology, the prevalence of endocrine side effects is rapidly increasing. As clinicians are nowadays frequently confronted with these side effects in routine clinical care, awareness, better knowledge of endocrine irAEs and their clinical presentation and diagnosis is crucial for an adequate management. In this short-review we give a compact overview of the recent recommendations for the management of endocrine irAE related to ICIs and highlight difficulties and uncertainties in current clinical practice.

Craniotomy

2019 ◽  
pp. 221-245
Author(s):  
Roxana Grasu ◽  
Sally Raty
Keyword(s):  
Risk Factors ◽  
Pain Management ◽  
Side Effects ◽  
Respiratory Depression ◽  
Pain Control ◽  
Sensory Nerves ◽  
Current Evidence ◽  
Multimodal Approach ◽  
Perivascular Nerves ◽  
Persistent Headache

This chapter discusses postcraniotomy headache (PCH), a common yet frequently underdiagnosed and undertreated occurrence, with up to 30% of patients experiencing persistent headache after surgery. The chapter identifies risk factors for the development of acute and persistent PCH and describes mechanisms for its development, such as injury to the sensory nerves supplying the scalp and underlying tissues or to the perivascular nerves that supply sensation to the dura mater. Pain management following craniotomy is a balancing act of achieving adequate analgesia while avoiding oversedation, respiratory depression, hypercapnia, nausea, vomiting, and hypertension. Current evidence suggests that a balanced, multimodal approach to the treatment of acute PCH is often required to optimize pain control, minimize undesired side effects, and prevent the development of persistent PCH.

Structure–function studies for the panacea, valproic acid

2009 ◽  
Vol 37 (5) ◽  
pp. 1126-1132 ◽  
Author(s):  
Nicole Terbach ◽  
Robin S.B. Williams
Keyword(s):  
Valproic Acid ◽  
Short Chain Fatty Acid ◽  
Structural Characteristics ◽  
Short Review ◽  
Hiv Treatment ◽  
Signalling Pathways ◽  
Structural Constraints ◽  
Therapeutic Action ◽  
Cellular Effects ◽  
Related Compounds

The anticonvulsant properties of VPA (valproic acid), a branched short-chain fatty acid, were serendipitously discovered in 1963. Since then, therapeutic roles of VPA have increased to include bipolar disorder and migraine prophylaxis, and have more recently been proposed in cancer, Alzheimer's disease and HIV treatment. These numerous therapeutic roles elevate VPA to near ‘panacea’ level. Surprisingly, the mechanisms of action of VPA in the treatment of many of these disorders remain unclear, although it has been shown to alter a wide variety of signalling pathways and a small number of direct targets. To analyse the mechanism of action of VPA, a number of studies have defined the structural characteristics of VPA-related compounds giving rise to distinct therapeutic and cellular effects, including adverse effects such as teratogenicity and hepatotoxicity. These studies raise the possibility of identifying target-specific novel compounds, providing better therapeutic action or reduced side effects. This short review will describe potential therapeutic pathways targeted by VPA, and highlight studies showing structural constraints necessary for these effects.

Postoperative analgesia after radical prostatectomy with high-dose intrathecal morphine and intravenous naloxone: A retrospective review

2018 ◽  
Vol 5 (6) ◽  
pp. 331-339 ◽  
Author(s):  
Annette Rebel, MD ◽  
Paul Sloan, MD ◽  
Michael Andrykowski, PhD
Keyword(s):  
Side Effects ◽  
Postoperative Pain ◽  
Pain Relief ◽  
Radical Prostatectomy ◽  
Respiratory Depression ◽  
Postoperative Analgesia ◽  
Intrathecal Morphine ◽  
Major Surgery ◽  
High Dose ◽  
The Mean

Background and methods: Intrathecal opioids (ITOs) have been used for decades to control postoperative pain. Intrathecal opioid dosing is limited, however, by opioid-related side effects, most importantly respiratory depression. To overcome these limitations, we combined intrathecal morphine with a continuous intravenous (IV) postoperative naloxone infusion to control opioid-related side effects. The purpose of this study is to document the efficacy and safety of high-dose intrathecal morphine combined with postoperative naloxone infusion to provide postoperative analgesia after major surgery. After IRB approval, a retrospective chart analysis was performed on 35 patients who had a radical prostatectomy from 2004 to 2006. All patients received a single injection of ITOs before anesthesia, a typical general anesthestic, followed by naloxone infusion at 5 μg/kg/h started 1 hour post-ITOs and continued for 22 hours postoperatively. The following information was collected: patient age, height, weight, anesthesia technique/time, and dose of ITOs given. Postoperative pain relief was assessed for 48 hours using the Visual Analog Score (VAS) for pain (0, no pain; 10, worst pain), perioperative opioid use, NSAID consumption, and ability of patient to ambulate. The safety of this novel treatment was assessed with opioid-related side effects and vital signs. All data are reported as mean (SD).Results: Mean ITOs given were morphine 1.3 (0.3) mg combined with fentanyl 56 (9) μg. The intrathecal morphine dose ranged from 0.8 to 1.7 mg. The mean worst pain VAS in the first 12 hours postoperatively was only 1.0 (1.7). The first NSAID dose was given 6.6 (3.1) hours post-ITOs. The first opioid on the floor was given an average of 22.6 (14.5) hours post-ITOs. A mean of only 5.7 (12.3) morphine equivalents were required on postoperative day 1 (POD 1). On POD 2, the mean worst pain VAS was only 2.6 (2.2) with only 5.7 (6.2) morphine equivalents needed to provide pain relief. On POD 1, 25 patients required no additional opioids for their entire hospital stay. Overall, 11 of 35 patients did not require any additional postoperative opioids. Thirtyfour patients (97 percent) were able to ambulate in the first 12 hours postoperatively. No opioid-induced respiratory depression was observed. Opioid-related side effects (pruritus, nausea) were infrequent and minor.Conclusions: High-dose ITOs combined with postoperative IV naloxone infusion provided excellent analgesia for radical prostate surgery. IV naloxone infusion appeared to control opioid side effects without diminishing the analgesia. No serious adverse effects were noted.

Pain Management for the Obese Sleep Apnea Patient

ICU Director ◽  
2012 ◽  
Vol 3 (2) ◽  
pp. 80-84 ◽  
Author(s):  
Mark A. Schumacher
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Pain Management ◽  
Side Effects ◽  
Respiratory Depression ◽  
Adult Population ◽  
Opioid Analgesic ◽  
Sleep Apnea Syndromes ◽  
Obese Patients ◽  
Obstructive Sleep

Currently, one third of the US adult population is considered obese. As such, obese patients are a rapidly growing population of patients being admitted to ICU. The problems in managing pain for these patients, primarily perioperative and hospital-associated respiratory depression, are becoming increasingly apparent. New approaches for pain management are intended to minimize the life-threatening side effects of traditional pain control drugs (opioids) and to increase the therapeutic options with nonopioid agents. This article ( a) reviews the pathophysiology of obstructive sleep apnea and other related sleep apnea syndromes, ( b) describes risk factors for perioperative and hospital-associated respiratory depression, ( c) reviews other significant side effects of opioid analgesic agents, and finally ( d) summarizes the emerging consensus for the use of multimodal analgesia for managing pain in obese patients with obstructive sleep apnea.

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