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The cross-talk between opioid and TLR4 receptor signaling systems
Hrdličková, Daniela ; Drastichová, Zdeňka (advisor) ; Březina, Jiří (referee)
Opioids are commonly used in clinical practice to treat acute and chronic pain. They stereoselectively bind to opioid receptors and trigger a signal cascade through inhibitory Gi/o- proteins, resulting in analgetic effects. However, their use can lead to various adverse effects, such as the development of addiction, analgetic tolerance, allodynia, hyperalgesia, constipation, and peripheral immunosuppression. Recent studies have found that opioids also bind non- stereoselectively to Toll-like receptor which belongs to innate immune system receptors recognizing lipopolysacharide. Findings suggest that some of these adverse effects may be a result of this interaction. It induces the expression of proinflammatory mediators in the central nervous system, but under certain conditions, it may also suppress inflammation. Communication between these different receptor systems occurs at multiple levels. Understanding these mechanisms could greatly benefit the development of new therapeutic approaches in opioid analgetic treatment, aiming to minimize their adverse effects, it could also lead to the therapeutic use of the antiinflammatory potential of opioids. Keywords: Opioids, Toll-like receptor 4, cellular signaling, inflammation, lipopolysaccharide, cytokine
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The effect of opioids on the immune system
Miniariková, Nina ; Novotný, Jiří (advisor) ; Cimermanová, Veronika (referee)
The use of opioids in medicine is necessary as they serve to suppress pain as a part of anesthesia notably during surgical procedures. After that, they help suppress pain during postoperative care and they are also prescribed to patients with chronic pain, for example in the final stages of cancer. However, opioids are among the most abused substances worldwide. The United States of America is facing an opioid epidemic, also called the opioid crisis, which began mainly with the excessive prescription of opioids and their subsequent misuse. It is clear that opioids affect the immune system which has been the subject of many recent studies. Different opioids have variable effects on the immune system. The understanding of their impact on the immune system could mean improvement of health care, and at the same time could present a basis for proposals of new treatment methods for some of the diseases. This bachelor thesis summarizes the available studies dealing with the influence and effects of various opioids on the cells of the immune system in order to better understand their importance and their use in practice. Keywords: opioids, immune system, inhibition, immunomodulation, phagocytes, lymphocytes
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The role of epigenetic mechanisms in the development of drug dependence
Durdilová, Marie ; Novotný, Jiří (advisor) ; Janoušková, Alena (referee)
The abuse of addictive substances is widely spread and carries numerous negative impacts, both on individuals and their surroundings. Some substances can lead to addiction after just a few doses, while for others, it may be a more prolonged process. However, the result is generally similar, with the prioritization of the drug or activity becoming the individual's main focus in life. This shift in priorities is linked to increased dopamine production due to the substance's effects, and the modulation of reward circuits in the brain. Changes in the connectivity and excitability of neurons in the mesolimbic and mesocorticolimbic dopamine systems lead to the development and maintenance of addiction. These neuronal changes are maintained in the body through epigenetic remodeling of chromatin. The pattern of epigenetic modifications, characteristic for a specific type of abused substance, can be passed on to the next generation, thereby increasing the potential for addiction development in offspring. Research on epigenetic modifications associated with addiction provides us with a deeper understanding of the neurophysiological changes accompanying drug addiction. At the same time, it raises the question of further treatment possibilities for drug addiction by targeting the epigenetic modifications that...
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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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