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Effect of morphine on the resistance of the heart to ischemia
Mošovská, Linda ; Neckář, Jan (advisor) ; Žurmanová, Jitka (referee)
2. Abstract Opioids are considered as dangerous and addictive substances, mainly due to synthetic opioids such as heroin. It was discovered, that these substances can play an important role in myocardial ischemia because they can limit the damage of the heart tissue that occurs during a heart attack. Since that heart attack is the most common cardiovascular disease, the protective effect is significant. Cardioprotective effect is mainly mediated through δ opioid receptors, but the few studies have shown cardioprotective effect mediated through κ opioid receptors. The protective effect occurs by activation of opioid receptors by their agonists (eg. morphine or TAN-67), either before ischemia (opioid preconditioning) or before reperfusion (opioid postconditioning). The signaling pathway of cardioprotection include mitochondrial KATP channel, Gi/o proteins, protein kinase C, tyrosine kinases and reactive oxygen species.
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Importance of particular regions of CNS in the development of opioid addiction
Vyvadilová, Tereza ; Hejnová, Lucie (advisor) ; Roubalová, Lenka (referee)
Opiods are used as the most powerful painkillers in the medicine. The mechanism of their effect is determined by binding to the opioids receptors located in the central nervous system and peripheral nervous system. The opioids have high potential to develop addiction. Significance of psychical addiction belongs to losing control above using and compulsive desire to obtain drug of abuse to achieve certain psychical state. The somatic part is increase tolerance demonstrating need of dose increasing to achieve required effect. This thesis summarizes knowledge about particular regions of the central nervous system which participate on developing of addiction as ventral tegmental area, nucleus accumbens, locus coeruleus, ventral pallidum and amygdala. It seems that main role in developing of addiction acts the mesolimbic reward system which relates with increased release of dopamine resulting in stimulation of the brain reward system.
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Bio-psycho-social-spiritual model in the buprenorphine substitutional treatment
Hanus, Richard ; Šotolová, Eva (advisor) ; Mlčková, Marie (referee)
This thesis is focused on the application of holistic, bio-psycho-social-spiritual model of dependence to concrete therapeutic method, namely to the substitution treatment of persons dependent on opiate addictive substances with synthetic opioid buprenorphine. The aim is to describe the essence of BPSS model of addiction, with the specifics of opiate addiction, and the treatment system based on it. Also, to show substitution therapy as one of the most effective methods that improves quality of a dependent person's life. Further, to confirm the need for a holistic perception of substitution treatment when ersatz drug use itself is not a real chance for dependent persons, unless such treatment is accompanied by psychosocial and spiritual therapeutic approach. Another objective is to map the risk that, in practice, the substitution therapy initiation in a holistic range brings in the context of contemporary reality. The work will consider approach bases to opiate addicts, especially the optics of lifelong abstinence versus controlled use, leading to better quality of dependent person's life. Theoretic base of the thesis is the theory of bio-psycho-social-spiritual model of dependence and the possibility of its application to the chosen concrete curative therapeutic approach - substitution treatment...
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Opioids as model drugs for exploring the mechanism underlying the development of drug dependence
Trojánková, Nikola ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
The aim of this bachelor thesis was to gather knowledge about the mechanisms of addiction, where opioids served as model compounds. Opioids are substances commonly used to treat acute and severe pain as in cancer treatment. However, long-term administration of these drugs killing, after a time reaches the ceiling, which is caused by rapid onset of analgesic tolerance and the slow development of tolerance to the secondary side effects. To achieve the same effect has to be constantly increasing dose, leading to the emergence and development of dependence. Mechanisms of drug addiction are still not fully elucidated, but recent studies agree that a very significant role in these events are membrane-bound opioid receptors and adenylyl cyclase signaling system that regulates intracellular levels of cAMP and CREB and FosB as transcription factors. Very important are the so-called epigenetic mechanisms, such as post-translational modification of histones and DNA or gene expression.
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Potential role of opioids in neuroprotection
Gebauer, Martin ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
The opioids have been used by mankind for more than two millennia, but effect and mechanism of their action on the cells has been unveiling in the last few decades. The mechanism itself is often still unknown, but its effect is observed only. There are several groups of opioid receptors which are able to bind opioids. These groups are characterized by their differe nt affinity to opioids, in some cases by their different effects on cells and by their representation in the various areas in the CNS. Thus, the effects induces by these opioid are very different in many cases. This thesis summarizes the current knowledge about coronary heart disease and the potential of opioids for the prevention and their effect during ischemia, also summarizes the effects of morphine on the CNS. During ischemia δ-opioid receptors play a major role, because they inhibit or block the proapoptotic effects of ischemia on many levels. These receptors are also involved in inducing and maintaining the animal hibernation and protect animal's body against very harmful effects of hibernation, e.g lack of oxygen and nutrients. Morphine is opioid which has been used as anesthetic for longest time. It is well-known opioid and it has the most known derivates. This thesis also summarizes most significant effects of morphine on...
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Opioid receptors and their signaling system in the myocardium
Ladislav, Marek ; Novotný, Jiří (advisor) ; Neckář, Jan (referee)
The main objective of this bachelor thesis is to systematically collect and sort information about opioid receptors and their signaling system in the myocardium. Heart activity is controlled mainly by adrenergic signaling, and this work therefore contains also some data concerning the characteristic and significance of other relevant receptors. For better understanding, general basic information about opioid system, especially about the receptors and their signaling, is also provided. Relatively little is known about opioid receptors in the myocardium even though these receptors may have an important role especially in various pathophysiological conditions. There can be several reasons for this. The possibility of further characterization of opioid receptors in the myocardium is rather difficult due to the relatively small number of these receptors in heart tissue. The situation is somewhat complicated also by some differences in the modulation of cardiac function among different species. The complete molecular mechanism by which opioid receptors act on the myocardium has not yet been fully uncovered. Especially in the case of humans this knowledge can be crucial, because these receptors and their ligands could be used for medical purposes.
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Molecular physiology of opioid receptors
Valný, Martin ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
The opioid receptors (OR) belong to the family of G protein-coupled receptors (GPCRs). ORs mediate the effects of the opioids, leading primarily to inhibition of neuroexcitability, predominantly through the class of the inhibitory G proteins Gi/Go. Cloning of ORs confirmed the existence of four subtypes of ORs, which mediate effects of different classes of opioid ligands. The major aim of this work is to summarize the current knowledge about characteristics and function of ORs at the molecular level. Acute exposition of ORs to their agonists results in activation of the signaling cascades that trigger mechanisms leading to analgesia. Chronic exposition of ORs to their agonists leads to desensitization and internalization of the receptors and induces adaptive changes in signal transduction system that suppresses the opioid action, and may result in the development of opioid tolerance and dependence. Although a big progress has been made in the field of understanding the molecular mechanisms of the OR-mediated signaling, there are still a lot of unresolved questions that are necessary to answer.
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Oxidative stress as the possible outcome of opioid treatment
Böhmová, Barbora ; Novotný, Jiří (advisor) ; Žurmanová, Jitka (referee)
Free radicals and reactive oxygen species are continuously formed in all aerobic organisms. They may be implicated in ethiology of some diseases such as cancer, atherosclerosis, rheumatoid arthritis, liver, renal, cardiovascular, and neurodegenerative diseases and premature aging. Free radicals and reactive oxygen species can also cause oxidative damage to important cellular components - proteins, lipids, and DNA. Cells are equipped with antioxidant systems to neutralize these radicals. The antioxidant system includes some vitamins (ascorbic acid, α-tocopherol, β-carotene) and enzymes, e.g., superoxide dismutase converting superoxide radical to hydrogen peroxide and molecular oxygen or catalase destroying H2O2. Another important H2O2-removing enzyme in human cells is glutathione peroxidase. Reduced activity of antioxidants leads to excessive production of free radicals resulting in oxidative stress. Opioids belong among pro-oxidants (chemicals inducting oxidative stress). Opioids can decrease activity of antioxidant enzymes and generate reactive oxygen species. The aim of this bachelor thesis is to gather information regarding the opioid ability to elicit oxidative stress. It briefly summarizes our current knowledge about opioids, oxidative stress, free radicals and antioxidants. Key words Opioids,...
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Clinical importance and mechanisms of action of morphine and methadone
Slušná, Michaela ; Hejnová, Lucie (referee) ; Novotný, Jiří (advisor)
This bachelor thesis deals with gathering the information regarding the clinical importance of opioid drugs, particularly morphine and methadone, and their mechanism of action. Awareness of health professionals and the general public on opioid is inadequate. This evokes unnecessary anxiety of uninformed patients by the treatment of this kind of drugs. This thesis contains information that should know each worker in the health sector. It deals with pharmacodynamics, which is important for understanding the effects of drugs, both biochemical and physiological as well as pharmacokinetics, which describes how the body compensates for the delivered drug. Usage of morphine and methadone is currently irreplaceable. Morphine is a strong analgesic effective control of pain of different origin. Methadone is used for the substitutive treatment of people addicted to opioids. The side effects occurring during the treatment with opioids are acceptable with regard to severe pain, which is attenuated by opioids.
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The application of opioids in crews of medical rescue service
MATOUŠEK, Jan
The aim set by this bachelor thesis is to survey the application of opioids in the emergency crews. To meet this objective, I posed two research questions. Research question Nr. 1: Are patients informed about the application of opioids? Research question Nr. 2: Do paramedics find out the effects of opioids administered to patients? Patients are entitled by law to information about administering any medicaments, according to Health Care of the Population Act. The back check of effects of medicaments administered is important for the check-up of the efficiency of the dose administered as well as the danger of undesired effects. Opioid substances are derived from morphine. Morphine, which is found in the juice of opium poppy, has been used throughout history to produce euphoric effects and especially as an analgesic. The reason for using analgesics is pain, and for that reason I explain here what pain is, how it is classified, measured and especially how it is soothed. Opioids are substances used for soothing severe pains for which non-opioid analgesics are insufficient. However, using these substances may result in addiction, and therefore manipulation with them is strictly controlled by law. To achieve the objective I conducted quantitative research, and data were collected by a secondary data analysis, the method of questioning and interview technique. Drawing on the research results that were obtained by observing paramedics and from interviews with their patients, it appears that it is necessary to inform patients that they are being administered an opioid substance. There are exceptional states when patients are not able to perceive such information and their consent to administering the medicine can be supposed. It was observed that paramedics make a back proof of the effects of the medicaments administered, and it was also found out that there are paramedics who, in the event that the dose of medicament is inefficient, do nothing more.
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