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Exploring the role of opioid signaling in modulation of microglial function
Mali, Akash Shivling ; Novotný, Jiří (advisor) ; Svoboda, Petr (referee) ; Machová Urdzíková, Lucia (referee)
Microglial activation is the most important component of neuroinflammation. It appears that opioids may affect microglial M1/M2 polarization in different ways depending on the type of receptor employed. In addition to opioid receptors, Toll-like receptor 4 (TLR4) of the innate immune system can also be activated by some opioid ligands and thus elicit specific cellular responses. Although opioid receptors (ORs) are known to regulate neurotransmission in various peptidergic neurons, their potential role in modulation of microglial function remains largely unknown. In this study, we investigated the effects of OR agonists, namely DAMGO, DADLE, and U-50488, on polarization and metabolic modulation of C8-B4 microglial cells. Our findings have revealed that opioids effectively suppress lipopolysaccharide (LPS)-triggered M1 polarization and promote the M2 polarization state. This was evidenced by decreased phagocytic activity, decreased production of nitric oxide (NO), diminished expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-86, and IL-12 beta p40, along with an increased migration rate and elevated expression of anti-inflammatory markers such as IL-4, IL-10, IL-13 arginase 1, and CD206 in microglia compared to cells influenced by LPS. Furthermore, we have demonstrated that...
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Psychological aspects of pharmacological pain management in palliative care
Trefná, Klára ; Niederlová, Markéta (advisor) ; Šivicová, Gabriela (referee)
This thesis deals with the psychological phenomena that are associated with the pharmacological pain management in a context of palliative care. The issue involves patient himself, but also a caregiver and a medical staff. The theoretical part of this thesis deals with pain and pharmacological pain management from a psychological point of view and focuses on a problematic attitude toward opioids. This thesis is based on the latest scientific findings by Czech and international researchers. This thesis also includes a research plan, which deals with the psychological factors that affect the attitude toward opioids in Czech environment.
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Opioid-induced microbial dysbiosis
Popjak, Šimon ; Drastichová, Zdeňka (advisor) ; Stehlíková, Zuzana (referee)
The aim of this bachelor thesis is to describe the consequences of opioids in relation to the gut microbiome. Chronic opioid use induces microbial dysbiosis in the gut, where both functional and structural changes in the composition of the microbiome occur. This disrupts gut homeostasis and leads to diseases. The diversity of microbial organisms decreases and the expression of neurotransmitters changes. Opioids interfere with the microbiomeň-gut-brain axis, which normally functions in symbiosis. They alter the composition of the gut microbiota, affect the function and structure of the gut epithelium and the expression of neurotransmitters in the nervous system. This thesis focuses primarily on the action of morphine, the action of which has been desribed the most. Keywords: opioids, microbiome, dysbiosis, microbiome-gut-brain axis, gut homeostasis
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Opioid dependence: mechanisms of development of withdrawal syndrome and its treatment
Hosenseidlová, Pavla ; Novotný, Jiří (advisor) ; Ujčíková, Hana (referee)
This work deals with opioids, opioid-induced withdrawal syndrome, and its treatment. Opioids are the most commonly used analgesics in medicine, and so far, there hasn't been a better alternative for them in most health cases. However, with long-term use, dependence can develop relatively quickly, and they have a high potential for abuse. When opioid use is discontinued, withdrawal syndrome occurs, and its symptoms resemble those of the flu, including muscle and joint pain, feeling cold and having a runny nose, nausea and vomiting, diarrhea, and tachycardia. These symptoms can be very intense and are often accompanied by psychological manifestations such as anxiety and depression. The treatment of opioid withdrawal syndrome is based on alleviating both physical and psychological symptoms. Most commonly, treatment involves using opioid agonists or antagonists with accompanying therapy for psychological manifestations. It is also important to include psychotherapy in the treatment process because the addiction in many cases stems from unresolved psychological or socio-economic issues.
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Opioid Crisis in the USA and its relevance to the Czech opioid situation
Sovík, David ; Kopsa Těšinová, Jolana (advisor) ; Nekola, Martin (referee)
The bachelor thesis focuses on the topic of opioid abuse in the United States of America and in the Czech Republic. The current situation of opioid abuse in the USA is called the "Opioid Crisis". The thesis describes the historical development of the problem, including its division into three main phases, in each of which a different opioid is the most abused. In the first phase, it is prescription opioids that are most commonly abused, while the last two stages are dominated by illicit opioid abuse of heroin and fentanyl. The identification of the primary causes of the Opioid Crisis is an important part of the thesis. Purdue Pharma is explicitely mentioned as having manufactured opioids that have directly contributed to the widespread abuse of opioids. Within the thesis, a typology is created in order to clarify which social groups in the USA are the most susceptible to becoming addicted to opioids. In the part of the thesis dedicated to the situation in the Czech Republic, a historical and current perspective of national opioid abuse is provided. Potential present and future threats that could lead to a worsening of the situation are also identified.
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Outcomes of take-home naloxone programme in Czechia after two years of operation
Lihtar, Štěpán ; Mravčík, Viktor (advisor) ; Janíková, Barbara (referee)
BACKGROUND: Opioid overdose represents significant public health burden in both the Czechia and the world in general. Although the prevalence in opioid use in our country is relatively low, it carries a disproportionate risk of health damage, including death from overdose. An effective intervention in the event of an opioid overdose is the administration of naloxone - an opioid antagonist that displaces the opioid from its receptors and interrupts the depression of the respiratory center. So-called take-home naloxone programs are based on the distribution of naloxone to lay people to administer naloxone when they witness an overdose. Take-home naloxone program was approved by the Czech Council of Government for the Coordination of Drug Policy in 2020, and its implementation began in April 2021. AIMS: The aim of this theses is to analyze the results of the take-home naloxone program in Czechia after two years of its operation. METHODS: The research part of this theses is based on a combination of two components - quantitative and qualitative. The data come from the Naloxone project reports and the Naloxone distribution project reports, which are filled by representatives of the programs involved in the project and then sent to the National Monitoring Center for Drugs and Addiction. The quantitative...
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The Causes of Higher Mortality Rate of African Americans in Case of Overdose During the Third Wave of Opioid Epidemic
Konečná, Kateřina ; Sehnálková, Jana (advisor) ; Szobi, Pavel (referee)
Diploma thesis addresses the topic of the opioid epidemic in the United States and focuses on the causes of the higher rate of overdose deaths among African Americans during the third wave of the epidemic. The opioid epidemic has claimed nearly one million victims since its onset in the late 1990s. In the public sphere, it is often associated with the white part of the population, which was hit the hardest in the early years of the epidemic due to the over- prescription of opioid painkillers. As the epidemic evolved from prescription drugs to illicit drugs such as heroin and fentanyl, its negative impact has spread to the rest of the US population, disproportionately affecting minority African American communities. During the third wave, opioid overdose death rates among African Americans increased disproportionately. This thesis examines the reasons for the higher rate of overdose deaths among African Americans. The thesis argues that African Americans are dying of overdose more because of the criminalization of drug addiction and the unavailability of drug addiction treatment. Based on available studies and academic articles, there is evidence that African Americans are criminalized for drug offenses and crimes more than the rest of the population, and drug addiction treatment is less accessible...
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Co-use of opioid analgesics with alcohol and/or benzodiazepines in patients with chronic non-cancer pain
Nováková, Daniela ; Mravčík, Viktor (advisor) ; Koutská, Kateřina Olga (referee)
Background: The problem of the simultaneous use (co-use) of benzodiazepines (BZD) and/or alcohol in patients with a diagnosis of chronic non-cancer pain (CHNCP) using strong opioid analgesics (OA) is still poorly mapped in the Czech Republic. Aims: To map the prevalence of co-use of BZDs and alcohol among patients with CHNNB taking long-term prescription OA. To determine differences between co-using groups and not-co-using patients and to determine predictors of co-use. Design and setting: The research is based on a secondary analysis of data collected in the period from March 2019 to December 2019 in the form of an anonymous questionnaire survey among patients of nine pain treatment centers in the Czech Republic. For research purposes, clinical and sociodemographic data related to co-use obtained from a semi-structured (anamnestic) questionnaire and data from the standardized questionnaires Screener and Opioid Assessment for Patients with Pain (SOAPP-R), Opioid Risk Tool (ORT) and Emotional Thermometers (ET) were analyzed. Particpants: The sample consisted of 305 respondents older than 18 years with diagnosed chronic pain and treated with strong OA for at least three moths. Measurements: Descriptive analysis was performed using descriptive statistics methods. Mann- Whitney test, chi-square test,...
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Molecular mechanisms of morphine action on the immune system
Zeťková, Anna ; Hejnová, Lucie (advisor) ; Vašek, Daniel (referee)
This paper focuses on the molecular effect of morphine, which is widely used for its analgesic and sedative properties. This makes it an important drug for the treatment of chronic and severe pain. In addition to its positive effects, the long-term administration of morphine in particular has its drawbacks, such as the rapid development of tolerance and dependence on it. Other negative effects include constipation, respiratory stagnation or vomiting. These effects are caused not only by the influence of morphine on nerve cells, but also on other cells of the body. This thesis is primarily concerned with the effect of morphine on microglia, which are not only involved in the immune response in the central nervous system, but also have an effect on pain perception or the development of tolerance. This is one of the main areas of research in the field of opioids, therefore, the aim of this thesis is to summarize the findings on the effect of morphine on microglia, which happens mainly through opioid receptors, toll-like receptors and purinoceptors.
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Toxicology of opioid analgesics and their impact on traffic accidents in the Moravian-Silesian Region
DOBIÁŠOVÁ, Marcela
The bachelor thesis is devoted to the issue of the use of opioid analgesics, their effect on traffic accidents and accidents caused under the influence. Opioid analgesics, which belong to the group of narcotic and psychotropic substances, are still a topical topic, as a large number of traffic accidents are caused by drivers who are under their influence. The theoretical part is devoted mainly to history, classification of opioid analgesics, distribution of narcotic and psychotropic substances, list of drugs containing narcotic and psychotropic substances in the Czech Republic, occurrence of side effects, addictions, route of administration, detection of addictive substances in the body, but also drug policy strategy in Moravian-Silesian Region, the Czech Republic and the European Union. The practical part is focused on the comparison of traffic accidents caused under the influence of opioid analgesics in the years 2014-2018 in the Moravian-Silesian Region. In the practical part, I processed the results based on the statistics of the Police of the Czech Republic. After evaluating the results, it was found that in the period 2014-2018, the number of traffic accidents under the influence of opioid analgesics increased in the Moravian-Silesian Region, but there was a decrease in traffic accidents caused under the influence of alcohol. At the same time, there was a reduction in the number of people who were slightly injured, severely injured and killed. The result also showed that the most accidents that were caused in the period under the influence of addictive substances were in the South Moravian Region.
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