Dissertations / Theses: 'Side effects of drugs'

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Chu, Yu-Hsuan. "Custom Fluorophores for Investigating the Cellular Uptake Mechanisms and Side-Effects of Pharmaceuticals." PDXScholar, 2015. http://pdxscholar.library.pdx.edu/open_access_etds/2343.

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There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others. The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically well-defined cationic drug conjugates. The long-term goal is to use the conjugates as tools to aid in elucidating the properties and identities of ion channels involved in the uptake of cationic pharmaceuticals into kidney and cochlear hair cells. This will shed light on the origin and potential prevention of unwanted side effects such as nephrotoxicity and ototoxicity associated with specific cationic drugs. A series of extended rhodamine analogs with reactive groups for biomolecule conjugation has been synthesized. These fluorophores show similar spectral properties to their prototype, Texas Red succinimidyl ester (TR-SE). However, they contain rigid linkers between the fluorophore and amine-reactive moiety. The resultant gentamicin conjugates of these materials are rigidified enabling one to assess channel pore dimensions without the confounding issue of conjugate folding. Preliminary cell studies are promising, as one observes reduced gentamicin uptake in both kidney and sensory hair cell upon systematically increasing the dimension of the fluorophore. This work has enabled us to tentatively assign the maximum dilated MET channel pore size as between 1.44 nm to 1.56 nm. However, this preliminary finding, though encouraging, needs further validation via ongoing studies with larger diameter fluorophore conjugates, A cisplatin-Texas Red conjugate has also been synthesized to enable studies of cellular uptake mechanisms. This conjugate preserves not only the spectral properties of Texas Red after conjugation, but also the cytotoxicity of cisplatin. This has been validated in zebrafish. The series of rhodamine probes that have been conjugated to gentamicin should be similarly useful for cisplatin studies. These studies are planned. Additional future work includes the synthesis of semi-flexible (glycol) and flexible (alkyl) linkers to evaluate structure-activity relationships.

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Gharanei, A. M. "Investigation into the cardiotoxic effects of doxorubicin and strategies for cardioprotection." Thesis, Coventry University, 2013. http://curve.coventry.ac.uk/open/items/ad712004-828e-4d9a-8ddb-17951146d414/1.

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Doxorubicin is one of the most effective anti-cancer agents; however its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Mitochondrial function and integrity are crucial for cellular processes in general and play an important role during diseased development. These characteristics of the mitochondria make them the prime target for treatments for majority of diseases and in particular of the cardiovascular system. The mitochondria are also considered to play an integral role in the manifestation of the cardiotoxic effects of compounds such as doxorubicin. The current project is designed to investigate the cardiotoxic effects of doxorubicin at tissue, cellular and protein level. In addition, it is investigated whether the inhibition of the mitochondrial permeability transition pore (mPTP) with cyclosporin A (CsA) or the inhibition of mitochondrial fission with the mitochondrial division inhibitor (mdivi-1) protects against the detrimental effects of doxorubicin on cardiac function. We also investigated whether co-treatment of doxorubicin with either CsA or mdivi-1 has any negative interaction with the cytotoxicity of doxorubicin against cancer cells. Langendorff results indicated that doxorubicin caused a time dependent reduction in the haemodynamic function of the heart as well as causing an increase in the infarct size to risk ratio in both naïve conditions and in conditions of ischaemia and reperfusion. Detrimental effects of doxorubicin on cardiac function were abrogated by co-treatment of doxorubicin with CsA or mdivi-1 in naïve conditions and in conditions of ischaemia and reperfusion. Cell viability data of isolated cardiac myocytes revealed that doxorubicin caused a concentration dependant decrease in the viability of neonatal cardiac myocytes as well as causing a reduction in the time taken to depolarisation and hypercontracture under sustained oxidative stress, all of which were prevented when co-treated with either CsA or mdivi-1. Doxorubicin significantly elevated the levels of p-Akt, p-Erk, p-Drp1 and p-p53. Co-treatment with CsA prevented the increase in the levels of p-Akt and p-Erk caused by doxorubicin in both naïve and IR condition whereas mdivi-1 prevented the increase in the levels of p-Erk, p-Drp1 and p-p53 and caused further increase in the levels of p-Akt. Using sinusoidal muscle length change during contraction and relaxation, it is demonstrated that doxorubicin caused a decrease in the power output, peak force and force during shorting. Detrimental effects of doxorubicin on work-loop contraction were abrogated when doxorubicin was co-administered with CsA. To conclude, results demonstrated that doxorubicin caused cardiotoxicity at tissue, cellular and protein level in both naïve conditions and in conditions of ischaemia and reperfusion injury. In addition, it is shown that the inhibition of mitochondrial permeability transition pore with CsA or the inhibition of the mitochondrial fission with mdivi-1 protect against doxorubicin-induced toxicity without affecting its anti-cancer properties.

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Bennett, Joanna. "Community psychiatric nurse practice in assessing side effects of antipsychotic drugs." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309696.

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Wu, Zimei, and n/a. "Formulation approaches to minimise injection site reactions of poorly soluble drugs." University of Otago. School of Pharmacy, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070503.122315.

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Purpose: The aim of this study was to investigate the usefulness of formulation approaches to minimise injection site reactions for poorly soluble drugs. The specific objectives were to modify the injection site reactions by identification of irritant components in the formulation and control of their release kinetics; and to gain understanding of formulation approaches to create a favourable microenvironment in the tissues allowing better tissue tolerance and drug absorption. Methods: Physicochemical properties of the model drug, ricobendazole (RBZ) were characterised using conventional methods. Three formulation approaches to minimise irritancy of the low pH RBZ solution were assessed. An in vitro method using 96-well microplates and a microtiter plate reader was used for detection of drug precipitation on dilution for formulation characterisation. Cellular damage by the formulations was investigated in L929 fibroblasts using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays. Tissue tolerance and pharmacokinetics were simultaneously investigated after subcutaneous injection in sheep. A low pH RBZ solution was used as a reference formulation. Results: Preformulation studies showed that RBZ was practically insoluble in water and oils, and was slightly soluble in commonly used co-solvents. Solubility was slightly improved by complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD, K₁:₁ = 311 M⁻�) or a combination of low pH (> 2) with surfactants or co-solvents. A U-shaped pH-solubility profile in aqueous solutions indicated that RBZ is an ampholyte. pKa values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 (basic) and 9.82 and 9.53 (acidic) respectively. The partition coefficient was 14.3 - 15.2 at pH 6 - 9 and less at higher or lower pH. In aqueous solutions, RBZ showed a V-shaped pH-degradation rate profile and was most stable at pH 4.8. Degradation pathways were identified as hydrolysis and oxidation. Three RBZ injectables (5%) were obtained by modification of the low pH RBZ solution; addition of 20% HP-β-CD, incorporation into a w/o emulsion, and a microemulsion (ME). On dilution with SPB, the onset time of drug precipitation was prolonged and the rate was reduced in the presence of HP-β-CD. The w/o emulsion had a low viscosity (< 60 mPa.s) and exhibited Newtonian flow. Drug release versus the square root of time was linear and the release rate could be adjusted by phase ratio and droplet size. Drug release was found to be by diffusion. A coarse emulsion layer appeared at the interface between the ME and buffer. Drug release from the ME was faster than from the emulsion and was linear with the square root of time. On titration into SPB, the three formulations showed controlling effects on the release of H₃O⁺ compared to the reference formulation. RBZ (0.1 mg/ml) was more toxic to L929 cells than the co-solvent propylene glycol (50 mg/ml). The formulations showed greater cytotoxicity than their vehicles in the order: ME > RBZ solution = emulsion > HP-β-CD. HP-β-CD and emulsion excipients showed little or no cytotoxicity. The MEs exhibited more toxicity in the LDH assay than in the MTS assay. A reversed phase HPLC assay for simultaneous determination of RBZ and its metabolite in sheep plasma using an isocratic system with UV detection was developed and used in the pharmacokinetic studies. Plasma samples were prepared by solid phase extraction. A suitable internal standard was selected by quantitative structure-retention relationships analysis. The composition of a ternary mobile phase was optimised with the assistance of multiple linear regression. The assays were linear over the concentration range 10 - 1000 ng/ml for both analytes (r > 0.999) with satisfactory inter-day and intra-day precision and accuracy (CV < 10%). The recoveries for all analytes were > 96%. A pilot study in sheep suggests that injection of the vehicles (the CD, emulsion and ME) caused virtually no pain on injection or site reactions. Both the reference formulation and its vehicle induced pain on injection and resulted in swollen tissues. Histology after two weeks showed granulation for the formulation, but not the vehicle. In contrast, animals showed virtually no injection site reactions with the ME and emulsion. The HP-β-CD formulation gave transient pain on injection but a two-fold increase in bioavailability compared with the reference. The emulsion produced sustained drug release and increased drug absorption. In the main study, the HP-β-CD vehicle showed good tissue compatibility. Irritation by the HP-β-CD formulation was attributed to the low pH. Cmax, tmax and AUC0-[infinity] for the reference formulation were 1.3 � 0.3 [mu]g/ml, 9.6 � 2.9 h and 36.7 � 9.2 [mu]g�h/ml respectively, while the corresponding data for the HP-β-CD formulation were 2.9 � 0.8 [mu]g/ml, 5.0 � 0.6 h and 54.5 � 15.3 [mu]g�h/ml respectively. The half-life following the injection of the HP-β-CD formulation (5.5 � 2.8 h) was shorter than that of the reference formulation (8.5 � 3.4 h). Conclusions: Injection site reactions may be minimised by identification of irritant components in a formulation and by controlling their release. Controlling the burst release of the poorly water soluble drug RBZ in a low pH solution could improve tissue tolerance and minimise post-injection precipitation, and hence increase drug bioavailability. In addition, HP-β-CD was a useful local injectable carrier which significantly enhanced the absorption of RBZ after subcutaneous injection in sheep.

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Khazaeinia, Tahereh. "Local and systemic gastrointestinal side effects of nonsteroidal anti-inflammatory drugs, NSAIDs." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0014/NQ59980.pdf.

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Lau, Phyllis Min-yu. "Adverse drug reactions in oncology." Monash University, Dept. of Pharmacy Practice, 2003. http://arrow.monash.edu.au/hdl/1959.1/5549.

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Olsén, Lena. "Drugs in horses : pharmacokinetics and pharmacodynamics /." Uppsala : Dept. of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/200737.pdf.

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Gouws, Stephanus Andries. "The impact of hospital surveillance programmes on the incidence of adverse drug reaction reporting in a South African teaching hospital." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/27186.

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Post-marketing surveillance refers to any non-experimental or observational study, method, or monitoring strategy that is applied to obtain information on drug experience (primarily adverse) after a drug has been approved for clinical use. One of the major problems in post-marketing surveillance studies is the lack or under-reporting of drug experiences by health care professionals. This study was developed to describe the impact of three different prescription event monitoring programmes on the reporting of adverse drug reactions (ADR's) in the hospital situation. The intensive ADR monitoring programme and two voluntary ADR monitoring programmes which followed were conducted in the medical wards of an urban teaching and referral hospital. All patients admitted to the designated wards were monitored by a dedicated pharmacist in the intensive programme, ward pharmacists in the first voluntary programme and by medical and nursing staff in the second voluntary programme. The pharmacist monitored a cohort of patients prospectively in two medical wards for a period of three months. The patient's record was linked with any suspected ADR. All details, i.e. patient drug orders, characteristics and ADR description, were recorded and then reported. From 228 patients monitored, 25 cases have been reported. The impact of the intensive ADR monitoring programme was a reporting rate of 11 percent. Reports were received on ADR's of a particularly mild, common and pharmacologically predictable (type A) nature. The first voluntary ADR monitoring programme comprised the reporting of suspected AD R's and the recording of drug orders for the patients and the patient characteristics. The ward pharmacists monitored for suspected AD R's in all patients during their regular ward rounds. Six cases were reported in a population of 1506 patients monitored during the three months. The reports were mainly on moderate to severe suspected AD R's of pharmacologically unpredictable (type B) nature. The rate of reports received by the surveillance unit in this study was 4 reports per ward pharmacist per annum. The second voluntary ADR monitoring programme comprised the prospective monitoring of 1555 patients by medical and nursing staff during their stay at the designated medical wards during the three month period. Patients were monitored for any ADR and when an ADR was suspected, the patient characteristics and drug orders were recorded and reported to the surveillance unit. Ten cases were reported represented by six reports from doctors and four by sisters. The reporting rate was 2 reports per doctor in four years and 3 reports for each member of the nursing team in 5 years. Reports were mainly received on moderate to severe suspected ADR's of a pharmacologically unpredictable (type B) nature.

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O'Brien, Michelle University of Ballarat. "A study of multiple perspectives and knowledge in adverse drug reaction decision-making : Volume 1." University of Ballarat, 2004. http://archimedes.ballarat.edu.au:8080/vital/access/HandleResolver/1959.17/12769.

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Injury and illness associated with drugs are major problems in Australia and around the world, despite significant developments in the area of adverse drug reaction (ADR) decision support technology. The aims of this thesis are: to investigate the ADR decision domain; to determine factors that may assist in the prevention, detection and management of ADRs; and, to inform the pre-requirements analysis phase of the development of decision support systems. An approach has been taken that permits open and grounded study of the decision environment. This approach can then be used to frame and inform the design of an ADR decision support system. Fifteen case studies that comprise self selected consumers, the treating medical practitioner/s and expert perspectives of a single instance of an ADR (fifteen in-depth consumer interviews, eight in-depth medical practitioner interviews and 30 expert written questionnaires), have been collected and analysed using a grounded theory approach, a symbolic interactionist theoretical framework and a social constructionist epistemology. The analysis was performed from three perspectives: individual case study analysis (all interviews for an instance of an ADR); group analysis (consumer, medical practitioner and expert views) and analysis combining the individual case studies and groups of data. Concepts, themes and theory have emerged from these data in the following areas: • the contribution of the differences in understanding of the core concepts within this domain, to misunderstandings between decision-makers; • the consumer as a diagnostic decision-maker in the ADR decision domain; • differential diagnostic strategies used by the consumers and medical practitioners; • complexities in the ADR decision domain that make diagnosis difficult; • the role of ADR information in consumer and medical practitioner decision-making; • decision types used by consumers and medical practitioners in the ADR decision domain; • resources used by consumers, medical practitioners and experts to inform their ADR decisions; • decision-making with partial knowledge of the consumer case history, drug behaviour and diseases; • the impact of suspected ADRs on consumers and on future decision-making; • medical practitioner/consumer decision-making models; and, • reasons for low ADR reporting and the impact on the development of new ADR knowledge. The results above suggest the following: • The ADR decision domain is more complex than the current ADR decision support focus and that broadening this focus may assist in providing a more complete and useful decision support solution. • Improving the prevention, detection and management of ADRs requires more than providing prescribers with up to date ADR information. Other important factors are sharing of information, awareness of the role of the consumer, a collaborative approach between the consumers and medical practitioners, and generation of new ADR knowledge. • A grounded theory analysis of case study data using the theoretical perspectives of social constructionism and symbolic interactionism provided insight into this domain from the perspectives of multiple decision-makers. This may be an approach that can be used by systems analysts to inform the requirements analysis phases of decision support within other domains. The results of this qualitative work are preliminary. Future work is required to confirm and expand these results.
Doctor of Philosophy

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O'Brien, Michelle. "A study of multiple perspectives and knowledge in adverse drug reaction decision-making : Volume 1." University of Ballarat, 2004. http://archimedes.ballarat.edu.au:8080/vital/access/HandleResolver/1959.17/14606.

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Injury and illness associated with drugs are major problems in Australia and around the world, despite significant developments in the area of adverse drug reaction (ADR) decision support technology. The aims of this thesis are: to investigate the ADR decision domain; to determine factors that may assist in the prevention, detection and management of ADRs; and, to inform the pre-requirements analysis phase of the development of decision support systems. An approach has been taken that permits open and grounded study of the decision environment. This approach can then be used to frame and inform the design of an ADR decision support system. Fifteen case studies that comprise self selected consumers, the treating medical practitioner/s and expert perspectives of a single instance of an ADR (fifteen in-depth consumer interviews, eight in-depth medical practitioner interviews and 30 expert written questionnaires), have been collected and analysed using a grounded theory approach, a symbolic interactionist theoretical framework and a social constructionist epistemology. The analysis was performed from three perspectives: individual case study analysis (all interviews for an instance of an ADR); group analysis (consumer, medical practitioner and expert views) and analysis combining the individual case studies and groups of data. Concepts, themes and theory have emerged from these data in the following areas: • the contribution of the differences in understanding of the core concepts within this domain, to misunderstandings between decision-makers; • the consumer as a diagnostic decision-maker in the ADR decision domain; • differential diagnostic strategies used by the consumers and medical practitioners; • complexities in the ADR decision domain that make diagnosis difficult; • the role of ADR information in consumer and medical practitioner decision-making; • decision types used by consumers and medical practitioners in the ADR decision domain; • resources used by consumers, medical practitioners and experts to inform their ADR decisions; • decision-making with partial knowledge of the consumer case history, drug behaviour and diseases; • the impact of suspected ADRs on consumers and on future decision-making; • medical practitioner/consumer decision-making models; and, • reasons for low ADR reporting and the impact on the development of new ADR knowledge. The results above suggest the following: • The ADR decision domain is more complex than the current ADR decision support focus and that broadening this focus may assist in providing a more complete and useful decision support solution. • Improving the prevention, detection and management of ADRs requires more than providing prescribers with up to date ADR information. Other important factors are sharing of information, awareness of the role of the consumer, a collaborative approach between the consumers and medical practitioners, and generation of new ADR knowledge. • A grounded theory analysis of case study data using the theoretical perspectives of social constructionism and symbolic interactionism provided insight into this domain from the perspectives of multiple decision-makers. This may be an approach that can be used by systems analysts to inform the requirements analysis phases of decision support within other domains. The results of this qualitative work are preliminary. Future work is required to confirm and expand these results.
Doctor of Philosophy

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Carstens, Hendrik Andries. "The management of a safe and cost effective conscious sedation unit." University of the Western Cape, 2016. http://hdl.handle.net/11394/5276.

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Philosophiae Doctor - PhD
Conscious sedation or moderate sedation and analgesia is an effective and popular alternative option for procedures outside the operating theater. If conscious sedation is a viable alternative to general anaesthesia then we as sedation practitioners must use safe sedation techniques in facilities that meet all the requirements for safe practice. Three studies were done to determine the safety and efficacy of conscious sedation outside the operating theatre. In the first study post sedation satisfaction in one hundred children aged 3-9 years was evaluated. It was extremely important to determine whether the combination of midazolam, ketamine and propofol, called an advanced sedation technique (SASA, 2015), can be safely used for paediatric sedation outside the operating theatre. The incidence of side-effects after conscious sedation using multiple drugs were documented. It is clear that intravenous sedation with midazolam, ketamine and propofol is safe and effective to use. There may be side effects but they are not long lasting and usually not life-threatening. In the second study intravenous sedation was administered to 447 adults (aged 18 years and older) using fentanyl (sublimazeR), ketamine (ketalar), midazolam (dormicum) and propofol (Diprivan) (FKMP) called an advanced sedation technique. Post sedation satisfaction, post sedation recovery on arrival home, and the relationship between side effects and different dental procedures were evaluated. The results of the study show that side effects are possible, and can be expected, when we use sedative and analgesic drugs for sedation. However, we report a low incidence of side effects when we compare it with other studies in literature as mentioned. It is known that the use of combinations of drugs may cause unforeseen synergistic pharmacological effects which can be lifethreatening. Our results show that the drugs used can be safely used for advanced sedation techniques. In trying to demonstrate the safety of sedative and analgesic agents used during sedation we looked at the haemodynamic parameters, duration of sedation, pulse rate and systolic blood pressure, in the third study. The sedation records of 335 patients for dental surgery were assessed for the period 2010 – 2011. Our results show the mean Duration of sedation is substantially and statistically significantly greater with combination FKMP than with the other combinations. The mean duration of sedation is not significantly different between ketamine and propofol (KP) and fentanyl, ketamine and propofol (FKP) (Figure 10). The use of polypharmacy regarding the combination of drugs, specifically FKMP, will cause a longer duration of sedation. This has implications for safety, as well as the side effect profile during and after sedation. When we use combinations of drugs patients were more comfortable which shows that we do not yet have a single drug that has all the characteristics of an ideal drug for sedation. Different combinations of drugs are used by other practitioners with a higher incidence of side effects. It is difficult to explain the higher values of blood pressures when all four drugs were used. It may have been a ketamine effect, although one would not expect this when using propofol with ketamine. In clinical terms the higher blood pressures are no reason for concern as all our patients were classified as ASA I and II. Our research study support the view that ketamine can be used safely outside the operating theatre with exciting possibilities for Third World countries for procedures outside the operating theatre. Sedation can be considered a reasonable alternative to general anaesthesia for certain surgical procedures in the Third World. Sedation will be an attractive option not only as far as costs are involved but also the availability of sedation providers. The important lesson from all the results is that sedation providers must be trained in procedural sedation as defined by all international sedation guidelines. We proved in this research study that sedation can be done safely, however we need to make a contribution to train sedation providers. Sedation will become an attractive alternative to general anaesthesia because of the low side-effect profile and high patient satisfaction. It is interesting that few studies are available that looked at this aspect of sedation. It is clear that a high side-effect profile can contribute to an unsafe sedation technique. Severe nausea and vomiting can cause numerous haemodynamic disturbances and dehydration. Our research study support the findings of the study by Lapere et al., (2015) that there is a high rate of patient satisfaction, and a low side-effect profile during and after sedation. This is an extremely important research study and the results are crucial as far as an option for healthcare in developing countries. Sub-Saharan Africa is a densely populated and resource poor subcontinent that provides unique challenges in patient care. These challenges include a lack of facilities and staff for the performance of operative as well as non-operative procedures. In conclusion, we feel that we are part of Sub-Saharan Africa with all the problems mentioned as far as provision of healthcare is concerned. This research study can make a crucial contribution to safe and cost-effective management of healthcare in Africa for procedures outside the operating theatre.

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Feigelman, Leonid. "PATTERNS OF USING ANTIHYPERTENSIVE DRUGS IN OUTPATIENT SETTINGS." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140618_233839-08839.

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We did not know the patterns of using antihypertensive drugs in outpatient settings in Israel that is why we raised a research aim to analyze the pattern of use of HBP in outpoint setting. In order to meet this aim we raised several research objectives:. 1) Does lifestyle modification is important for the patient for blood pressure control? 2) Do the patients need to change their medication at set of time until BP goals reached? 3) Does the use of more than one drug would help achieving better HBP results? Does the use of single doses combination would have better affect then using fixed dose combination? 4) How often noncompliance take in HBP control? 5) How many patients suffer from side effects? Methods: a questionnaire composed of 36 questions and qualitative statistical analysis.
Mes nežinojome, kad naudojant antihipertenzinių vaistinių preparatų ir ambulatorinėmis Izraelyje, kuris yra, kodėl mes iškėlė Tyrimo tikslas išanalizuoti naudojimo HBP Išėjo taško nustatymo modelį modelius. Siekiant įgyvendinti šį tikslą, mes iškėlė kelis mokslinių tyrimų tikslams:. 1) Ar gyvenimo būdo pakeitimas yra svarbus kraujospūdžio kontrolės pacientui? 2) Ar pacientai turi pakeisti savo vaistą esant rinkinį, kol pasiekė BP tikslai? 3) Ar iš daugiau nei vieno narkotiko naudojimas padėtų pasiekti geresnių HBP rezultatus? Ar vienos dozės deriniu būtų geriau veikia tada naudojant fiksuotų dozių derinys? 4) Kaip dažnai nesilaikymo imtis HBP kontrolės? 5) Kiek pacientų kenčia nuo šalutinio poveikio? Metodai: Klausimynas sudarytas iš 36 klausimų ir kokybinio statistinę analizę.

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Church, Donna Lea. "Depot medroxyprogesterone acetate discontinuation after weight gain in 17-19 year old adolescent girls." CSUSB ScholarWorks, 2002. https://scholarworks.lib.csusb.edu/etd-project/2047.

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Depot medroxyprogesterone acetate (DMPA) is a long acting progesterone only contraceptive agent. Side effects such as irregular bleeding patterns and weight gain are attributed to discontinuation. The purpose of this study was to describe depot medroxyprogesterone acetate discontinuation after weight gain in 17 to 19 year-old adolescent girls.

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Kunac, Desirée L., and n/a. "Adverse drug events and medication errors in a paediatric inpatient population." University of Otago. Dunedin School of Medicine, 2005. http://adt.otago.ac.nz./public/adt-NZDU20060707.161220.

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Background. Medication-related patient injuries (adverse drug events, ADEs) are an important problem in all hospitalised populations; however, the potential for injury is reported to be greater in children than adults. Many ADEs are due to error and therefore could be prevented. Data regarding the risk factors (or predictors) for these events in paediatric inpatients is limited. It was hypothesised that "identification of risk factors for ADEs and medication errors in the paediatric inpatient setting will inform likely prevention strategies". Aims. To determine the frequency, nature and risk factors for ADEs and potential ADEs occurring in a paediatric inpatient population; to assess the vulnerable processes in the neonatal intensive care unit (NICU) medication use process; and to provide recommendations for the targeting of likely prevention strategies. Setting. A general paediatric ward (PW), postnatal ward (PNW) and NICU of a University- affiliated urban general hospital. Design. There were two study components: the medEVENT study which involved identification of actual ADEs and potential ADEs over a twelve week period, through prospective review of medical records, medication charts and administration records along with voluntary and solicited staff report and parent interview; and the FMEA study which used a proactive risk assessment technique, Failure Mode and Effect Analysis (FMEA), to rank all potential failures in the NICU medication use process according to risk. Results. In the MedEVENT study 3160 prescription episodes were reviewed (which represented 520 admissions, 3037 patient-days) and revealed a total of 67 ADEs and 77 potential ADEs. The greatest number of events occurred in NICU with very few events in the PNW. However, paediatric surgical admissions experienced the highest rate of ADEs per 1000 patient-days (80) as compared to medical (65) then NICU admissions (19). Over half of the ADEs were deemed preventable, 38 (57%), with the �more serious� ADEs more likely to be preventable than �not serious� ADEs. The impact on hospital resources was considerable with the cost attributed to extra bed days due to ADEs to be $NZD 50,000. Dosing errors were the most common type of error, particularly when prescribing and administering medications. Antibacterial and narcotic analgesics were commonly implicated, as was the intravenous route of administration. Few events were related to unlicensed use of medications. For ADEs, the major risk factors when analysed by admission, were greater medication exposure and increasing age; by prescription, were increasing age, oral route and narcotics and antibacterial agents; for paediatric ward admission, were increasing age and increased length of stay; and for NICU admission, no major risk factors emerged. For potential ADEs, the major risk factors when analysed by admission were greater medication exposure; by prescription, were junior prescriber, intravenous route, narcotics and antibacterials; for paediatric ward admission, were junior prescriber and narcotics; and for NICU admission were antibacterials, electrolytes and umbilical venous catheter administration. Neither ADEs nor potential ADEs were associated with unlicensed use of medicines or high alert status drugs. The FMEA study identified 72 potential failures in the NICU medication use process with 193 associated causes and effects. Multiple failures were possible in the process of �prescribing medication� and in the process of �preparation of medication for administration�. The highest ranking issues were found to occur at the administration stage. Common potential failures related to errors in the dose, timing of administration, infusion pump settings and route of administration. Conclusions. Analysis of the risk factors of ADEs and potential ADEs found that the most vulnerable processes were when prescribing and when preparing a medicine for administration; especially when involving narcotic and antibacterial agents and for children with greater medication exposure Strategies that selectively target these high risk areas are therefore likely to have the greatest impact on preventing drug-related injuries in hospitalised children.

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Silber, Yvonne Beata. "The acute side effects of d-amphetamine and methamphetamine on simulated driving performance, cognitive functioning, brain activity, and the standardised field sobriety tests." Australasian Digital Theses Program, 2006. http://adt.lib.swin.edu.au/public/adt-VSWT20070319.105603/index.html.

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Thesis (PhD) - Swinburne University of Technology, 2006.
Typescript. [Submitted for the degree of] Doctor of Philosophy, Swinburne University of Technology - 2006. Includes bibliographical references (p. 253-290).

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Tolle, Michelle D. "In vivo Dilantin treatment alters expression levels and nuclear localization of cyclins A and B1 during mouse preimplantation embryo development." Muncie, IN : Ball State University, 2009. http://cardinalscholar.bsu.edu/677.

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Sachikonye, Tinotenda Chipo Victoria. "Development and assessment of minocycline sustained release capsule formulations." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1013127.

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The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.

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18

Ahmed, Al-Obeidi Fahad. "Design, synthesis, conformation and biological activities of cyclic alpha-melanotropin and related compounds." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184445.

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This research initiated an investigation of the structural relationships between melanocyte stimulating hormone (α-MSH) and its melanin dispersion on lizard (Anolis carolinensis) and frog (Rana pipiens) skins bioassays as representing models for mammalian and amphibian melanocytes, respectively. From previous extensive structure-activity relationships of α -MSH together with the theoretical modeling we were able to design a group of linear and cyclic peptides related to "4-10" fragment analogues of α -MSH. The solid phase synthesis of α -MSH and its related analogues using the p-methyl-benzhydrylamine resin was accomplished. The C-terminal carboxamide and N-terminal acetylamide were maintained in all peptides synthesized. The cyclic peptides were prepared in solution phase using the linear peptides generated by solid phase. All the cyclization were done by using the hydrochloride salts of the peptide and DMF as solvent with diphenylphosphoryl azide (DPPA) as a coupling reagent in the presence of K₂HPO₄ as a base. The yields of the cyclic peptides were in the range of 30-40 percent. In all the synthesized peptides the replacement of D-Phe⁷ with L-Phe⁷ causes reduction in the potency of the peptide on lizard or frog skins bioassays. Also, the reduction or increase in ring size in the cyclic peptide from a 23 membered ring diminishes the biological effect of the peptide under testing.

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19

Shoemaker, Danton L. "Examination of Sexual Differences in the Acute Effects of Haloperidol on Licking." Thesis, University of North Texas, 2015. https://digital.library.unt.edu/ark:/67531/metadc822780/.

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Schizophrenia is a debilitating psychiatric condition affecting almost one percent of the US population. Typical antipsychotics (e.g., haloperidol) have been in use for several decades and are generally very effective in treating the emotional and cognitive effects of schizophrenia, but are used as the last line of treatment due to their severe extrapyramidal motor side effects under chronic exposure. The present study was conducted to investigate the role of sex in determining the oromotor side effects of typical antipsychotics via measuring different behavioral dimensions of male and female Sprague-Dawley rats licking sucrose after haloperidol treatment. The results showed a stronger sensitivity in female rats than male rats within total licking responses and inter-lick intervals. The present results suggest closer attention needs to be paid to the role that sexual hormones play in the motor slowing and behavior-reducing effects of antipsychotics.

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20

Binks, Stephen Peter. "Absorption, toxicity and deposition of transition metal based pharmaceuticals following oral administration." Thesis, University of Surrey, 1988. http://epubs.surrey.ac.uk/847165/.

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The aim of this dissertation was to study the absorption, and subsequent toxic side effects of transition metal based pharmaceuticals following oral administration to rats. Administration of cisplatin (30mg/kg), carboplatin (37mg/kg) and iproplatin (42mg/kg) by oral gavage resulted in their rapid absorption so that respective peak blood levels of 2.63mug platinum/ml, 1.48mug platinum/ml and 3.13mug platinum/ml were achieved within 2-4 hours. Approximately 3-4% of the dose was excreted in the urine, but the major route of elimination was the faeces (>75%). This indicated that although rapid, absorption was relatively poor. Absorption was enhanced by employing a period of starvation prior to administration. A series of novel platinum (IV) mixed amines were absorbed to a greater extent than cisplatin and its congeners, carboplatin and iproplatin. However, absorption was somewhat slower with peak blood levels being attained some 24 hours after administration. Of the other transition metal complexes studied, auranofin and ruthenium acetylacetonate were particularly well absorbed so that peak blood levels of 12.53mug gold/ml and 6.4mug ruthenium/ml were achieved respectively. Urinary clearance of the ruthenium complex was especially significant with up to 45% of the administered dose being eliminated by this pathway within 48 hours. In vitro everted gut sac and in situ perfusion techniques confirmed the in vivo finding that cisplatin is absorbed from the small intestine more readily than carboplatin. No evidence for active or carrier-mediated transport was found and kinetic studies confirmed that absorption was by passive diffusion. Toxicology studies after oral administration of cisplatin (57 or 30mg/kg) or carboplatin (282mg/kg) indicated that the toxicities associated with the perenteral use of the complexes would also apply to the oral route. This was exemplified by the fact that oral cisplatin was profoundly nephrotoxic, whereas carboplatin was not. In addition, gastro-intestinal toxicity manifested as acute necrotizing enteritis and ulcerogenicity of the stomach was potentiated by the oral route. Studies in the ferret indicated that cisplatin is significantly more emetogenic than carboplatin. Examination of liver morphology indicated changes, such as mitochondrial swelling and vesiculation of the endoplasmic reticulum, that might indicate a higher incidence of hepatotoxic responses associated with administration of platinum complexes by the oral route. Both cisplatin and carboplatin induced a degree of myelosuppression but the most pronounced haematological lesion associated with oral administration was severe erythrocytosis which occurred as a result of a dehydration related decrease in plasma volume. Electrothermal atomic absorption analysis of tissues excised from cisplatin and carboplatin rats indicated that platinum deposition was highest in the kidney. In an attempt to explain the prolonged retention of cisplatin in this organ, the intracellular location of the compound was studied using electron microprobe analysis and subcellular fractionation. The various lysosome populations of the proximal tubule were identified as sites of concentration of platinum and it was hypothesised that sequestration within these organelles might be an important mechanism of detoxification.

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21

Padayachee, Vaneshree. "Awareness regarding non-steroidal anti-inflammatory drug-related side effects in Johannesburg, South Africa." University of Western Cape, 2021. http://hdl.handle.net/11394/8370.

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>Magister Scientiae - MSc
Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most commonly used medications globally, as they are highly effective and easily accessible. The NSAIDs are indicated for mild to moderate pain management. The increasing incidence of NSAID related side effects and hospitalisations has raised a concern about these medications’ safety. The prevalence of these side effects has drastic consequences to a challenged South Africanpublic healthcare system. The implications of not treating severe, potentially preventable upper gastrointestinal complications attributed to NSAIDs’ consumption continue to be a significant problem that healthcare professionals (HCP) face.

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22

Young, Shawquia Elithia. "Dual Mechanism Analgesia-Enhancing Agents." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd/1166.

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Currently, there is an increasing need for novel analgesics that are potent but lack undesired side effects. Recent studies have shown that both 5-HT3 receptors and α2B- adrenoceptors play a role in antinociception. MD-354, N-(3-chlorophenyl)guanidine, has a high-affinity both for 5-HT3 and α2B- adrenoceptors and could be viewed as the first example of a rather selective 5-HT3/α2B- adrenoceptor ligand. MD-354, inactive by itself, potentiates the antinociceptive effects of an inactive dose of clonidine in the mouse tail- flick assay. An attempt to determine the underlying mechanism of this potentiating effect was the purpose of the present investigation. The studies focused on an examination of: i) MD-354 in the mouse hot-plate assay, ii) a more lipophilic analog of MD-354 in the tail-flick assay, iii) various analogs of MD-354 with different binding profiles in both mouse tail-flick and hot-plate assays. The present investigation suggests that both 5-HT3 and α2B- adrenoceptors are playing a role in the potentiation of clonidine analgesia by arylguanidines such as MD-354. Arylguanidines might represent a unique class of analgesia-enhancing agents with a dual (5-HT3/α2- adrenoceptor) mechanism of action.

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23

張杰能. "近十六年(1989-2005)香港中藥不良反應事故的分析研究." HKBU Institutional Repository, 2006. http://repository.hkbu.edu.hk/etd_ra/741.

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24

Hansson, Emma K. "Pharmacometric Models for Biomarkers, Side Effects and Efficacy in Anticancer Drug Therapy." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170738.

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New approaches quantifying the effect of treatment are needed in oncology to improve the drug development process and to enable treatment optimization for existing therapies. This thesis focuses on the development of pharmacometric models for biomarkers, side effects and efficacy in order to identify predictors of clinical response in anti-cancer drug therapy. The variability in myelosuppression was characterized in six different cytotoxic anticancer treatments to evaluate a model-based dose individualization approach utilizing neutrophil counts as a biomarker. The estimated impact of inter-occasion variability was relatively low in relation to the inter-individual variability, indicating that myelosuppression is predictable from one treatment course to another. The approach may thereby be useful for dose optimization within an individual. To further study and to identify predictors for the severe side effect febrile neutropenia (FN), the relationship between the shape of the myelosuppression time-course and the probability of FN was characterized. Patients with a rapid decline in neutrophil counts and high drug sensitivity were identified to have a higher probability of developing FN compared with other patients who experience grade 4 neutropenia. Predictors of clinical response in patients receiving sunitinib for the treatment of gastro-intestinal stromal tumor (GIST) were identified by the development of an integrated modeling framework. Drug exposure, biomarkers, tumor dynamics, side effects and overall survival (OS) were linked in a unified structure, and univariate and multivariate exposure variables were tested for their predictive capacities. The soluble biomarker, sVEGFR-3 and tumor size at start of treatment were found to be promising predictors of overall survival, with decreased sVEGFR-3 levels and smaller baseline tumor size being predictive of longer OS. Also hypertension and neutropenia was identified as predictors of OS. The developed modeling framework may be useful to monitor clinical response, optimize dosing in sunitinib and to facilitate dose individualization.

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25

Zayed, Aref. "Development of ICP-MS assays for the study and prediction of the efficacy and side effects of Pt-based drugs in cancer chemotherapy." Thesis, Loughborough University, 2012. https://dspace.lboro.ac.uk/2134/9446.

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Pt-based drugs are important cytotoxic agents that are used in the chemotherapeutic regimes of ~50% of all cancer patients. However, the efficacy of these drugs is often limited by drug toxicity and tumour resistance. Determination of the cellular pharmacokinetics and pharmacodynamics of Pt-drugs is important for understanding their molecular mechanisms of action and toxicity, and may be used, therefore, to predict the outcome of the treatment. ICP-MS is the most sensitive technique for the determination of Pt in biological samples and can offer robust, fast and accurate quantitations for studying pharmacokinetics and pharmacodynamics of Pt-drugs in patients. This thesis describes the development of a set of ICP-MS based assays for the determination of Pt-DNA adducts and Pt sub-cellular distribution in leukocytes of cancer patients and human cancer cell lines following treatment with Pt-based chemotherapy. It is ultimately aimed to use these assays in the clinic to predict the effectiveness and toxicity of Pt-based chemotherapy in individual patients, and offer those who would respond to the treatment personalised drug doses. Alternatively, patients who would not benefit from these drugs would be offered other forms of treatment. Pt DNA adduct formation was determined in leukocytes from patients undergoing Pt-based chemotherapy demonstrating signiﬁcant inter-patient variability and excellent reproducibility of the assay. The sensitivity of the technique enabled quantitation of as little as 0.2 Pt adducts per 106 nucleotides using 10 µg of patient DNA. It was shown that Pt/P ratio was robust against DNA matrix effects, and was considered more reliable approach, with Eu as internal standard, for estimating Pt adducts per nucleotide compared to using Pt data in combination with DNA concentration measured by UV. Comparison of in vivo Pt-DNA adduct formation with the patients clinical notes suggested possible correlation between the adduct formation in leukocytes and toxicity. Speciation methods employing HPLC with complementary ICP-MS and ESI-Ion Trap-MS detection were developed and used for characterisation of oxaliplatin bi-functional adducts with mono-nucleotides and di-nucleotides. Further, a fast and sensitive LC-ICP-MS assay was developed and used for the quantification of oxaliplatin GG intra-strand adducts in human cancer cell lines. The assay, which has a detection limit of 0.22 Pt adduct per 106 nucleotides based on a 10 μg DNA sample, is suitable for in vivo assessment of the adducts in patients undergoing oxaliplatin chemotherapy. Combining the ICP-MS quantitation with a cell fractionation procedure allowed, for the ﬁrst time, the detailed quantitation of entire sub-cellular Pt-drug partitioning in patient leukocytes in vivo, and in human cancer cell lines in vitro, following exposure to variety of Pt-drugs. The studies showed that Pt broadly follows the total protein content of the individual sub-cellular compartments with the majority being scavenged in the cytosol compartment.

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26

Passare, Galina. "Drug use and side effects in the elderly : findings from the Kungsholmen Project /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-365-5/.

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27

Yang, Jing. "Determination of peramivir and its toxicokinetics in beagle dogs." Thesis, University of Macau, 2011. http://umaclib3.umac.mo/record=b2524966.

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28

Abjaude, Samir Antonio Rodrigues [UNESP]. "Avaliação do uso profilático de omeprazol em pacientes internados no hospital estadual Américo Brasiliense." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/127881.

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Made available in DSpace on 2015-09-17T15:26:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-04. Added 1 bitstream(s) on 2015-09-17T15:45:57Z : No. of bitstreams: 1 000842358_20160501.pdf: 688314 bytes, checksum: c0e58d7c09371b47da4b8dfd21b13c6b (MD5) Bitstreams deleted on 2016-05-04T13:08:28Z: 000842358_20160501.pdf,. Added 1 bitstream(s) on 2016-05-04T13:09:32Z : No. of bitstreams: 1 000842358.pdf: 2362291 bytes, checksum: 607ef5f590e4380cff19bf4d439fa958 (MD5)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Introdução. O omeprazol é amplamente administrado e, na maioria das vezes, o uso é efetivo e seguro. No entanto, estudos avaliaram que o omeprazol foi o medicamento mais relacionado com a admissão hospitalar devido RAM. Tais RAM talvez possam ser explicadas devido ao uso abusivo ou prescrição irracional de omeprazol. Todavia, não foi avaliado o risco e o benefício do uso profilático do omeprazol, considerando o uso aprovado e o uso não aprovado, e as consequências para a segurança do paciente. Objetivo. Identificar e avaliar o risco de ocorrência de EAM e o benefício através da efetividade do uso profilático de omeprazol em pacientes internados. Método. Conduziu-se um estudo coorte observacional de agosto a outubro de 2013 e dezembro/2013 a maio/2014, no Hospital Estadual Américo Brasiliense. Os pacientes internados foram classificados em três grupos: a) uso de omeprazol profilático aprovado, b) uso de omeprazol profilático não aprovado; c) não uso de omeprazol. Foram excluídos os pacientes que fizeram uso de omeprazol não profilático. Os pacientes foram monitorados diariamente com auxílio do roteiro de investigação adequado previamente. Os dados foram tabulados segundo a presença ou ausência de efetividade e de eventos adversos nos três grupos. Resultados. Foram monitoradas 427 hospitalizações, sendo 136 expostos ao omeprazol profilático não aprovado e 52 expostos ao omeprazol profilático aprovado. Identificaram-se apenas dois casos de suspeita de inefetividade e 14 de eventos adversos. Observou-se diferença significativa na concentração sérica da creatinina e ureia para os pacientes que usavam omeprazol profilático aprovado. Conclusão. Há duas vezes mais pacientes expostos ao omeprazol profilático não aprovado comparado ao uso aprovado. Não houve associação do omeprazol profilático com fator de risco, no entanto, houve diferença significativa no...
Introduction. Omeprazole is a widely used drug; in most cases, it is effective and safe. However, studies have found omeprazole to be the drug most frequently related to hospital admissions due to adverse drug reactions (ADRs). The ADRs could have occurred as a result of abuse or irrational prescribing of omeprazole. Despite that possibility, the risks and benefits of prophylactic omeprazole considering the approved and off-label uses and the potential consequences for patient safety have not been assessed. Objective. To identify and assess the risk of adverse drug events and the benefit provided by the effective use of prophylactic omeprazole in hospitalized patients. Methods. This observational cohort study was conducted from August to October 2013 and December 2013 to May 2014 at the Américo Brasiliense State Hospital. The inpatients were classified into three groups: a) approved use of prophylactic omeprazole b) off-label use of prophylactic omeprazole, and c) not using omeprazole. Patients who used no prophylactic omeprazole were excluded. The patients were monitored daily with the aid of a pre-established research protocol. Data were tabulated according to drug effectiveness or ineffectiveness and presence of adverse events in the three groups. Results. A total of 427 hospitalized patients were monitored in the study. Of these, 136 patients were exposed to prophylactic omeprazole used off-label and 52 exposed to on-label use of prophylactic omeprazole. Two cases of suspected ineffectiveness and 14 adverse events were recorded. There was a significant difference in serum creatinine and urea for patients using on-label prophylactic omeprazole. Conclusion. There are twice as many patients using off-label prophylactic omeprazole as patients using it for approved indications. There was no association of prophylactic omeprazole with risk factors, but there was a significant difference in the increase in serum creatinine and urea for ...
FAPESP: 13/12681-2

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29

Mpofu, Tariro Ann-Maureen. "Comparison of the neuroprotective potential of theanine and minocycline." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1003253.

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Stroke is one of the most common causes of disability and death worldwide. The most commonly experienced stroke in the clinical setting is focal ischaemia in which the middle cerebral artery (MCA) is occluded and leads to a complex series of various pathophysiological pathways that ultimately lead to neuronal cell death. Several studies have been conducted on various therapeutic agents in the search for a neuroprotective drug and various animal models have been used to carry out this research. While theanine, a component of green tea and minocycline, a tetracycline antibiotic, have been shown to possess some neuroprotective properties, the mechanisms by which these two agents carry out these effects still remains unclear. The objectives of this study were to investigate the mechanisms by which these drugs carry out these neuroprotective effects and their neuroprotective ability in a MCA occlusion model of focal ischaemia. Ischaemia leads to oxidative stress due to the imbalance of free radicals and the endogenous antioxidant defence system. An antioxidant assay using the stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH●) radical was used to assess the antiradical properties of each drug. It was found that minocycline showed superior antioxidant activity in vitro when compared to theanine. Further studies on the drugs‟ ability to attenuate the Fenton reaction (in which iron catalyses the formation of reactive species) were elucidated using electrochemical analysis, UV/VIS studies, ferrozine and ferritin assays. It was found that minocycline, in contrast to theanine, was able to bind to iron ions and thus potentially prevent the participation of iron in metal catalysed radical reaction. The antioxidant activity of both drugs was further investigated by assessing their effect on cyanide-induced superoxide generation and quinolinic acid (QA)-induced lipid peroxidation (LP). Experimental evidence shows that both drugs had no significant effect on the generation of superoxide in vitro and that there was a significant decrease in LP for minocycline in vitro and theanine in vivo. The metal binding and antioxidant properties were postulated to be a possible mechanism through which these agents reduced lipid peroxidation. A study was conducted to determine the effects of the drugs on the biosynthesis of the neurotoxin, QA and it was found that minocycline increases the levels of holoenzyme activity of tryptophan-2, 3-dioxygenase (TDO) in vitro and that theanine reduces the levels of the same enzyme in vivo after treatment for 10 days. TDO is the enzyme that converts tryptophan to other products that enable enzymatic activity to change it to QA. Minocycline was thought to bring about this effect as it has been shown from preceding experimental studies that it is an effective reducing agent. Theanine on the other hand is hypothesised to bring about a reduction in holoenzyme activity by changing the binding of tryptophan to the enzyme or affecting the radicals that participate in the enzymatic degradation of tryptophan. A focal ischaemic model of stroke was induced by occluding the MCA. Histological examination of the hippocampus post -ischaemia shows a reduction in the size of the infarct after pre-treatment with minocycline only. A further study into the effects of the drugs on the generation of superoxide and on the levels of the endogenous glutathione after a stroke was carried out. Pre-treatment of the animals with either theanine or minocycline showed no significant effects on the generation of the radical species or of the endogenous antioxidant which ruled out these as a mechanism of neuroprotection of both drugs, post-ischaemia.The findings of this study provide novel information on the possible mechanisms by which both theanine and minocycline act to bring about neuroprotection. In particular in this study, pre-treatment with minocycline has shown promise in the focal ischaemic model of stroke.

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30

Sodha, Anirudhasingh. "DEVELOPMENT AND COMMERCIALIZATION OF HEPATOCYTE TARGETED DRUG DELIVERY VEHICLE FOR PHARMACEUTICAL APPLICATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1247192896.

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31

阮貞. "2006-2011年我國中藥與西藥不良反應頻度和强度的回顧性比較研究." Thesis, University of Macau, 2012. http://umaclib3.umac.mo/record=b2590331.

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32

Jarernsiripornkul, Narumol. "Pharmacist input into patients' self-reporting of adverse drug reactions." Thesis, Robert Gordon University, 1999. http://hdl.handle.net/10059/2717.

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Adverse drug reactions (ADRs) are common and should be reported to the CSM, particularly for newly marketed drugs. There is under-reporting of ADRs by doctors. Involving the patient in self-reporting, particularly when initiated by pharmacists is feasible and could help to improve reporting rates. This study investigated a comprehensive checklist questionnaire listed symptoms in all body systems to facilitate patient self-reporting using both established and new 'black triangle' centrally-acting drugs. Symptoms reported were compared to their documentation in medical notes and for new drugs to reports from other sources. A novel classification system for ADRs was developed to take account of the minimal data available and used to evaluate the potential accuracy of symptom attribution by patients. An external comparison of a sample of symptom classifications by an ADR expert was also obtained. The questionnaire was sent to 464 patients prescribed carbamazepine, sodium valproate, trazodone, doxepin and co-proxamol from three participating medical practices in a pilot study. Subsequently, it was sent to all patients (n=2307) prescribed tramadol, fentanyl patch, venlafaxine, nefazodone, citalopram, moclobemide, gabapentin, lamotrigine and topiramate from 79 participating medical practices in Grampian during January-March 1997. The overall response rates were 44.6% (n=207) for the pilot study and 36.3% (n=837) for the main study. The most frequently reported symptoms were: drowsiness for carbamazepine, unusual tiredness for sodium valproate, constipation for co-proxamol, dry mouth for trazodone, doxepin, tramadol, venlafaxine, nefazodone, moclobemide and citalopram, weight gain for gabapentin, loss of memory for lamotrigine, weight loss for topiramate and constipation for fentanyl patch. Overall only 22.4% (522/2330) of symptoms reported by patients were recorded by GPs in the 310 medical notes accessed. In general, common symptoms were reported more frequently by patients than in CSM reports and PEM data. Patients tended to report minor and known ADRs which bothered them, while CSM and PEM reports received were of more severe ADRs. Respondents were more likely to report symptoms (6040/8630,70%) potentially caused by the study drugs than those not to be caused by the study drugs. Moderate agreement (Kappa = 0.4-0.5) was found between expert and researcher classifications of symptom causality. It is suggested that interpretation by pharmacists of patient self-reporting using the checklist questionnaire could result in much higher ADR reporting rates, in particular for new drugs.

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Au, Wai Ling. "Investigations of the bioavailability/bioequivalence of topical corticosteroid formulations containing clobetasol propionate using the human skin blanching assay, tape stripping and microdialysis." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1003221.

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Currently, clinical trials in patients are required by most regulatory authorities for the assessment of bioequivalence of topical products where the drug is not intended for systemic absorption. Hence there is a dire need for suitable methods for the assessment of bioavailability and bioequivalence of such products since clinical safety and efficacy studies are expensive, time-consuming and require very large numbers of patients. Except for topical corticosteroid products where the human skin blanching assay/vasoconstrictor assay has been approved by the US FDA for bioequivalence assessment of those products, no other method has been “officially” approved for use in those investigations. However, a few alternative methods such as tape stripping and microdialysis have been pursued and considered to have the potential for use in ioequivalence/bioavailability studies. The human skin blanching assay was used to assess the bioequivalence of commercially available topical products containing 0.05% clobetasol propionate. Both visual and chromameter data were obtained and a commercially available topical corticosteroid product, Dermovate® cream was used as both the “Test” and the “Reference” product. The results indicated that both visual and chromametric assessments were comparable to each other and that either could be used for the assessment of the bioequivalence of topical products containing clobetasol propionate. The screening procedure was optimized to identify potential “detectors” for inclusion in the bioequivalence studies. This resulted in fewer subjects being required in a bioequivalence pivotal study, still having the necessary power to confirm bioequivalence using the human skin blanching assay. Another objective of this research was to re-visit tape stripping and other possible alternative methods such as dermal microdialysis and to optimize these procedures for bioequivalence assessment of topical formulations where the drug is not intended for systemic absorption. In the past few decades, tape stripping has been used to investigate bioavailability/bioequivalence of various topical formulations. This technique involves the removal of the stratum corneum to assess drug penetration through the skin. A draft FDA guidance for tape stripping was initially published but was subsequently withdrawn due to high variability and poor reproducibility. This research project used an optimized tape stripping procedure to determine bioavailability and establish bioequivalence between three commercially available formulations containing 0.05 % m/m clobetasol propionate. Furthermore, tape stripping was validated by undertaking a study to assess the bioequivalence of a 0.05% topical cream formulation (Dermovate® cream) using the same cream as both the “Test” and “Reference” product, in which bioequivalence was confirmed. The findings highlight the potential of tape stripping as an alternative method for the assessment of bioequivalence of clobetasol propionate formulations and may possibly be extended for use in other topical products. Microdialysis is another useful technique that can assess the penetration of topically applied substances which diffuses through the stratum corneum and into the dermis. Microdialysis has previously been successfully used for in vivo bioavailability and bioequivalence assessments of topical formulations. However, the drugs which were under investigation were all hydrophilic in nature. A major problem with the use of microdialysis for the assessment of lipophilic substances is the binding/adherence of the substance to the membrane and other components of the microdialysis system. As a result, this necessitates the development of a microdialysis system which can be used to assess lipophilic drugs. Intralipid® 20% was investigated and successfully utilized as a perfusate to recover a lipophilic topical corticosteroid, clobetasol propionate, in microdialysis studies. Hence, the bioavailability of clobetasol propionate from an extemporaneous preparation was determined in healthy human volunteers using microdialysis. These findings indicate that in vivo microdialysis can be used to assess lipophilic drug penetration through the skin. A novel approach to investigate drug release from topical formulations containing 0.05% clobetasol propionate using in vitro microdialysis was also undertaken. The in vitro findings were found to be in agreement with the results obtained using tape stripping to assess bioequivalence of the same commercially available products, namely Dermovate® cream, Dovate® Cream and Dermovate® ointment. These results indicate the potential to correlate in vitro with in vivo data for bioequivalence assessment of such topical dosage forms.

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Duz, Marco. "Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7581/.

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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.

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Thornborrow-Geswind, Kirsten. "Evaluation of medicine safety reporting systems in South Africa." Thesis, Nelson Mandela Metropolitan University, 2017. http://hdl.handle.net/10948/21439.

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Pharmacovigilance is “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem”. To date, no comprehensive study has been performed to evaluate the pharmacovigilance system in the public health sector in South Africa. The primary aim of this study was to evaluate the current status of pharmacovigilance systems within the public healthcare sector in South Africa, and the level of functioning of these systems, in order to provide relevant recommendations, where necessary, for improvement, using the Indicator-based Pharmacogivilance Assessment Tool (IPAT). National and provincial entities were deemed compulsory (n=14), while facilities were selected via random, stratified sampling to obtain a representation at each facility level (n=101). The IPAT was amended for relevance at each level of data collection. Indicators are classified as core and supplementary and compliance with core indicators shows the level of functioning National entities obtained an IPAT score of 36 out of a maximum of 72, achieving 50% compliance. Province D and Province G obtained overall IPAT scores of 29 and 12 respectively out of a maximum of 40, achieving an overall 72.5% and 30% compliance respectively Results at provincial and facility levels were not fully representative due to a limited response rate of 22.2% and 65.3% respectively. Regional/tertiary facilities and district facilities displayed increased awareness and implementation of pharmacovigilance activity than the lower levels of Community Health Centres (CHCs) and Primary Health Centres (PHCs). South Africa”s public healthcare system possesses the infrastructure for a well functioning pharmacovigilance system. However there are gaps in level of functioning at a national, provincial and facility level. Addressing these gaps would show a marked improvement in the system and go a long way towards the contribution of medicine safety information not only locally, but to aid other developing nations.

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Wang, Chen. "High-throughput prediction and analysis of drug-protein interactions in the druggable human proteome." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5509.

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Drugs exert their (therapeutic) effects via molecular-level interactions with proteins and other biomolecules. Computational prediction of drug-protein interactions plays a significant role in the effort to improve our current and limited knowledge of these interactions. The use of the putative drug-protein interactions could facilitate the discovery of novel applications of drugs, assist in cataloging their targets, and help to explain the details of medicinal efficacy and side-effects of drugs. We investigate current studies related to the computational prediction of drug-protein interactions and categorize them into protein structure-based and similarity-based methods. We evaluate three representative structure-based predictors and develop a Protein-Drug Interaction Database (PDID) that includes the putative drug targets generated by these three methods for the entire structural human proteome. To address the fact that only a limited set of proteins has known structures, we study the similarity-based methods that do not require this information. We review a comprehensive set of 35 high-impact similarity-based predictors and develop a novel, high-quality benchmark database. We group these predictors based on three types of similarities and their combinations that they use. We discuss and compare key architectural aspects of these methods including their source databases, internal databases and predictive models. Using our novel benchmark database, we perform comparative empirical analysis of predictive performance of seven types of representative predictors that utilize each type of similarity individually or in all possible combinations. We assess predictive quality at the database-wide drug-protein interaction level and we are the first to also include evaluation across individual drugs. Our comprehensive analysis shows that predictors that use more similarity types outperform methods that employ fewer similarities, and that the model combining all three types of similarities secures AUC of 0.93. We offer a first-of-its-kind analysis of sensitivity of predictive performance to intrinsic and extrinsic characteristics of the considered predictors. We find that predictive performance is sensitive to low levels of similarities between sequences of the drug targets and several extrinsic properties of the input drug structures, drug profiles and drug targets.

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Amanzadi, Amirhossein. "Predicting safe drug combinations with Graph Neural Networks (GNN)." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-446691.

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Many people - especially during their elderly - consume multiple drugs for the treatment of complex or co-existing diseases. Identifying side effects caused by polypharmacy is crucial for reducing mortality and morbidity of the patients which will lead to improvement in their quality of life. Since there is immense space for possible drug combinations, it is infeasible to examine them entirely in the lab. In silico models can offer a convenient solution, however, due to the lack of a sufficient amount of homogenous data it is difficult to develop both reliable and scalable models in its ability to accurately predict Polypharmacy Side Effect. Recent advancement in the field of representational learning has utilized the power of graph networks to harmonize information from the heterogeneous biological databases and interactomes. This thesis takes advantage of those techniques and incorporates them with the state-of-the-art Graph Neural Network algorithms to implement a Deep learning pipeline capable of predicting the Adverse Drug Reaction of any given paired drug combinations.

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Villafranca, Steven Wayne. "The effect of early psychostimulant treatment on abuse liability and dopamine receptors." CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/2824.

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Examines whether the reinforcing properties of drugs of abuse were altered in adulthood by methylphenidate, more commonly known as Ritalin. Subjects were 108 rats of Sprague-Dawley descent (Harlan). Methylphenidate, or saline was administered daily to the subjects from the postnatal period (11-20 days old). The rats preference for morphine during early adulthood was measured using conditioned place preference. The number of dopamine D₂ receptors was measured in each rat and the correlation between receptor number and morphine preference was determined. Results indicate that rats pretreated with methylphenidate showed greater preference for morphine than saline pretreated rats and suggests that exposure to methylphenidate during the postnatal period increases the rewarding value of morphine.

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Boyda, Heidi Noel. "A preclinical evaluation of antipsychotic drug-induced metabolic side-effects : a focus on glucose dysregulation and insulin resistance." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44909.

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Second generation antipsychotic (SGA) drugs represent the pharmacotherapeutic drug treatment of choice for patients affected by psychosis. Despite their clinical benefits, some SGA drugs are associated with significant metabolic side-effects including weight gain, glucose intolerance, insulin resistance and hypertriglyceridemia that ultimately increases patient risk for the development of cardiometabolic disorders. Although abundant, preclinical literature on SGA drug-induced metabolic side-effects has failed to characterize an underlying mechanism to glucose derangements. We therefore completed seven studies to validate the use of a rat model of SGA drug-induced glucose dysregulation that will establish a consistent approach for future mechanistic studies of insight. We employed the intraperitoneal glucose tolerance test, the hyperinsulinemic-euglycemic clamp, as well as surrogate measures of metabolic indices to ascertain the pharmacological effects of SGA drugs specifically on hyperglycemia, glucose intolerance and insulin resistance. Antipsychotic drugs of higher metabolic liability (olanzapine and clozapine) parallel what is observed in humans and induced substantial glucose intolerance and insulin resistance that was both dose and time dependent. Antipsychotic drugs of lower metabolic liability (risperidone and haloperidol) were associated with modest effects on metabolic indices, compared to controls. The newer SGA drugs also demonstrated drug-dependent effects: iloperidone was associated with profound glucose intolerance and insulin resistance, while asenapine-induced effects were minimal, compared to controls. As for antipsychotic polypharmacy (the practice of when two antipsychotic drugs are administered together), either administrations of clozapine and haloperidol or clozapine and risperidone were found to cause substantially greater glucose intolerance, relative to the administration of a single drug. Chronic treatment with olanzapine produced sustained glucose intolerance and insulin resistance; whereas intermittent olanzapine treatment led to a first-ever report of the sensitization of glucose metabolism. Lastly, different classes of antidiabetic drug treatments or daily exercise intervention was found to partially ameliorate the metabolic side-effects of olanzapine. These data confirm that our current rodent paradigm parallels clinical literature. Our studies have provided insight into the metabolic influence of SGA drugs on peripheral target tissues such as hepatic, pancreatic and skeletal muscle. Ultimately, these results will further understanding of the underlying mechanisms by which SGA drugs cause glucose dysregulation and insulin resistance.

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Winter, Lara. "Characterisation of the neurosteroid analgesic alphadolone." Monash University, Dept. of Anaesthesia, 2004. http://arrow.monash.edu.au/hdl/1959.1/9669.

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Sevak, Rajkumar Joytishchandra. "Effects of streptozotocin and food restriction on dopamine clearance and on the behavioral effects of dopaminergic drugs : a dissertation /." San Antonio : UTHSC, 2006. http://proquest.umi.com/pqdweb?did=1251825011&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.

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42

Prinz, Stephanie Jeanette [Verfasser]. "Analysis of Genotype-Phenotype Relationships based on Drug Side Effects, Disease Symptoms and Mouse Phenotypic Traits / Stephanie Jeanette Prinz." München : Verlag Dr. Hut, 2016. http://d-nb.info/1106593456/34.

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43

Vivas, Ana Paula Molina. "Avaliação de manifestações bucais em pacientes pediátricos submetidos ao transplante hepático." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-13092012-112810/.

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Introdução. O transplante hepático se tornou a principal opção terapêutica para o tratamento de várias doenças hepáticas. Subsequentemente ao transplante, é necessária a administração de terapia imunossupressora para evitar rejeição ao órgão transplantado. A avaliação odontológica é fundamental para eliminação ou prevenção do surgimento de focos infecciosos. Além disso, faz-se necessário o acompanhamento dos efeitos colaterais em cavidade bucal relacionados ao uso de drogas imunossupressoras. Objetivo. Avaliar as condições odontológicas previamente ao transplante hepático e identificar as alterações bucais apresentadas após o transplante hepático. Pacientes e métodos. Foi realizado estudo retrospectivo de 265 pacientes pediátricos submetidos ao transplante hepático no Hospital A.C. Camargo, São Paulo-SP, entre janeiro de 2002 e dezembro de 2009. As informações clínicas como idade, gênero, diagnóstico da doença hepática, data do transplante, terapia imunossupressora (tipo, dose e duração), tratamento odontológico e a presença de alterações bucais pós-transplante foram coletadas dos prontuários médicos. Análise estatística foi realizada buscando estabelecer informações relevantes quanto aos riscos e possíveis fatores preditivos para o desenvolvimento de manifestações bucais. Resultados. A idade ao transplante hepático variou de 3,5 a 210,7 meses, tendo uma mediana de 15,5 meses. Dos 265 pacientes, 150 pacientes (56,6%) eram do gênero feminino e 165 (62,3%) eram leucodermas. Dentre as doenças de base, a atresia de vias biliares foi a mais frequente, acometendo 170 (64,1%) pacientes. Um total de 73 pacientes foi avaliado pelo Departamento de Estomatologia previamente ao transplante, e destes, 34 (46,6%) apresentaram cárie. Quanto à presença de pigmentação dentária por bilirrubina, 172 pacientes foram avaliados e destes, 100 (58,1%) apresentaram pigmentação. Em relação à presença de hipoplasia do esmalte dentário, a alteração foi observada em 56 (34,4%) de 163 pacientes. Interessantemente, dos 100 pacientes com pigmentação dentária por bilirrubina, 97 apresentavam doenças colestáticas (p<0,001). Quanto aos casos de hipoplasia do esmalte, 52 (92,9%) pertenciam ao grupo de doenças colestáticas (p<0,001). Diversas alterações em mucosa bucal foram encontradas após o transplante, sendo que 135 pacientes apresentaram alguma complicação. Dos 265 pacientes estudados, o principal problema encontrado foi infecção pelo vírus herpes simples, em 48 pacientes, sendo que 66,7% dos casos ocorreram a partir de 12 meses após o transplante. A segunda doença infecciosa mais comum em cavidade oral foi a candidose, observada em 39 pacientes e 61,5% dos casos ocorreram durante o primeiro semestre pós-transplante. Importantes alterações bucais foram encontradas em pacientes em uso de tacrolimus, como a hipertrofia de papilas linguais, ressecamento labial, edema labial, fissuras labiais, fissuras linguais, queilite angular, mucosa com aspecto de pedra de calçamento e língua despapilada, observadas em 45, 39, 39, 38, 27, 11 e 6 pacientes, respectivamente. A hiperplasia gengival medicamentosa foi observada em 13 pacientes, sendo que 8 estavam em uso de ciclosporina e todos os outros usavam além do tacrolimus, drogas bloqueadoras de canais de cálcio. A complicação que ocorreu mais precocemente nos pacientes após o transplante foi a doença linfoproliferativa, em média 5,2 meses após o transplante. Conclusões. O índice de cáries foi elevado refletindo as precárias condições de saúde bucal desses pacientes. A pigmentação por bilirrubina e a hipoplasia do esmalte são alterações dentárias associadas a doenças colestáticas, embora possam ocorrer em pacientes portadores de doenças não colestáticas que apresentem períodos de colestase. As lesões orais infecciosas mais frequentes foram lesões pelo vírus herpes simples e a candidose. A hiperplasia gengival medicamentosa está relacionada ao uso de ciclosporina e de bloqueadores de canais de cálcio, sendo que o tacrolimus não parece induzir o efeito. Alterações bucais como hipertrofia de papilas linguais, fissuras linguais, língua despapilada, ressecamento, edema e fissuras labiais; queilite angular e mucosa oral com aspecto de pedra de calçamento foram encontradas em pacientes em uso de tacrolimus e ocorreram normalmente 2 anos após o transplante.
Introduction. Liver transplantation has become the main therapeutic option for the treatment of various liver diseases. Subsequent to transplantation, it is necessary to administer immunosuppressive treatment to avoid rejection of the graft. A dental evaluation is critical to eliminate or prevent the emergence of infectious foci. Moreover, it is necessary to monitor the side effects in the oral cavity related to the use of immunosuppressive drugs. Objectives. To evaluate the dental conditions prior to liver transplantation and to identify oral abnormalities presented after liver transplantation. Pacients and methods. A retrospective study of 265 pediatric patients who underwent liver transplantation at Hospital A.C. Camargo, São Paulo-SP, between January 2002 and December 2009 was performed. Clinical information such as age, gender, diagnosis of liver disease, date of transplantation, immunosuppressive therapy (type, dose and duration), dental treatment and oral changes after transplantation were collected from medical records. Statistical analysis was performed in order to establish relevant information about the risks and possible predictive factors for the development of oral manifestations. Results. The age at liver transplantation ranged from 3.5 to 210.7 months, with a median of 15.5 months. Of the 265 patients, 150 patients (56.6%) were female and 165 (62.3%) were Caucasian. Among the diseases, biliary atresia was the most frequent, with 170 (64.1%) patients. A total of 73 patients were evaluated by the Department of Stomatology prior to transplantation, and 34 (46.6%) children presented caries. Regarding the presence of tooth pigmentation caused by bilirubin, 172 patients were evaluated and out of these, 100 (58.1%) had pigmentation. Regarding the presence of enamel hypoplasia, the change was observed in 56 (34.4%) of 163 patients. Interestingly, of the 100 patients with bilirubin pigmented teeth, 97 had cholestatic diseases (p<0.001). Of the cases of enamel hypoplasia, 52 (92.9%) belonged to the group of cholestatic diseases (p<0.001). Several changes in the oral mucosa were found after transplantation, whereas 135 patients had some complication. Of the 265 patients studied, the main problem was herpes simplex virus infection, found in 48 patients and 66.7% of cases occurred after 12 months from transplantation. The second most common infectious disease was oral candidiasis, observed in 39 patients and 61.5% of cases occurred during the first six months post-transplant. Important oral abnormalities were found in patients using tacrolimus such as the hypertrophy of the lingual papillae, dry lips, swollen lips, fissured lips, fissured tongue, angular cheilitis, cobblestoning and loss of tongue papillae, observed in 45, 39, 39, 38, 27, 11 and 6 patients respectively. The drug-induced gingival overgrowth was observed in 13 patients, and 8 of them were taking cyclosporine, while all others were using tacrolimus in addition to calcium channel blockers. The post-transplant complication that occurred earlier in patients was lymphoproliferative disease, on average 5.2 months after transplantation. Conclusions. The rate of caries was high, reflecting poor oral health status of these patients. The bilirubin pigmentation of teeth and enamel hypoplasia are abnormalities associated with cholestatic diseases, although they may occur in patients with non-cholestatic diseases that present periods of cholestasis. The most common oral infectious lesions were caused by herpes simplex virus and candidiasis. The drug-induced gingival overgrowth is associated with the use of cyclosporin and calcium channel blockers, while tacrolimus does not appear to induce this effect. Oral alterations such as hypertrophy of the lingual papillae, fissured tongue, loss of tongue papillae, dry, swollen and fissured lips; angular cheilitis and cobblestoning were found in patients using tacrolimus and usually occured after 2 years from transplantation.

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He, Bing. "Toward precision medicine: a combination of leflunomide and ligustrazine attenuates progressive bone erosion in rheumatoid arthritis patients with high baseline serum c-reactive protein level." HKBU Institutional Repository, 2016. https://repository.hkbu.edu.hk/etd_oa/316.

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Leflunomide is widely prescribed for Rheumatoid Arthritis (RA) patients in China. However, a number of RA patients still demonstrated progressive bone erosion (PBE+) after receiving Leflunomide in our clinical data. Moreover, the PBE+ is predicted by high baseline serum CRP level (CRPBH). Further, the changes of serum bone resorption marker (Tartrate-resistant acid phosphatase 5b, TRAP5b) strongly correlated with those of CRP in PBE+ RA patients during Leflunomide treatment. Those were consistently observed in collagen-induced-arthritis (CIA) rats. To precisely address the issue, we screened a series of marketed drugs combined with Leflunomide to inhibit CRP production and CRP-related osteoclastic signaling pathway using bioinformatics analysis. Ligustrazine was postulated as an optimal candidate drug. In vitro studies demonstrated that the combination of Ligustrazine and Leflunomide not only suppressed hepatic CRP production, but also suppressed CRP-related osteoclastic signaling and osteoclast activities. In vivo studies showed that the combination attenuated bone erosion in CIA rats. Further, the randomized parallel controlled clinical trial in 120 CRPBH RA patients showed that the combination therapy reduced serum CRP levels and attenuated bone erosion in those patients (ChiCTR-TRC-10001014). Together, this work presents a precision combination therapy for PBE+ in CRPBH RA patients.

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Mathu, Alexander Muchugia Nganga. "Structural analysis of effects of mutations on HIV-1 subtype C protease active site." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1004073.

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HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.

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Algoul, Saleh. "Optimal Multi-Drug Chemotherapy Control Scheme for Cancer Treatment. Design and development of a multi-drug feedback control scheme for optimal chemotherapy treatment for cancer. Evolutionary multi-objective optimisation algorithms were used to achieve the optimal parameters of the controller for effective treatment of cancer with minimum side effects." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5499.

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Cancer is a generic term for a large group of diseases where cells of the body lose their normal mechanisms for growth so that they grow in an uncontrolled way. One of the most common treatments of cancer is chemotherapy that aims to kill abnormal proliferating cells; however normal cells and other organs of the patients are also adversely affected. In practice, it's often difficult to maintain optimum chemotherapy doses that can maximise the abnormal cell killing as well as reducing side effects. The most chemotherapy drugs used in cancer treatment are toxic agents and usually have narrow therapeutic indices, dose levels in which these drugs significantly kill the cancerous cells are close to the levels which sometime cause harmful toxic side effects. To make the chemotherapeutic treatment effective, optimum drug scheduling is required to balance between the beneficial and toxic side effects of the cancer drugs. Conventional clinical methods very often fail to find drug doses that balance between these two due to their inherent conflicting nature. In this investigation, mathematical models for cancer chemotherapy are used to predict the number of tumour cells and control the tumour growth during treatment. A feedback control method is used so as to maintain certain level of drug concentrations at the tumour sites. Multi-objective Genetic Algorithm (MOGA) is then employed to find suitable solutions where drug resistances and drug concentrations are incorporated with cancer cell killing and toxic effects as design objectives. Several constraints and specific goal values were set for different design objectives in the optimisation process and a wide range of acceptable solutions were obtained trading off among different conflicting objectives. Abstract v In order to develop a multi-objective optimal control model, this study used proportional, integral and derivative (PID) and I-PD (modified PID with Integrator used as series) controllers based on Martin's growth model for optimum drug concentration to treat cancer. To the best of our knowledge, this is the first PID/I-PD based optimal chemotherapy control model used to investigate the cancer treatment. It has been observed that some solutions can reduce the cancer cells up to nearly 100% with much lower side effects and drug resistance during the whole period of treatment. The proposed strategy has been extended for more drugs and more design constraints and objectives.

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Zein, Naïmah. "“CpdX”, a non-steroidal Selective Glucocorticoid Receptor Agonistic Modulator (SEGRAM) selectively triggers the beneficial anti-inflammatory activity of glucocorticoids, but not their long-term debilitating effects." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ088.

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Lors de la liaison d’un glucocorticoïde (GC) naturel ou synthétique (par exemple, la Dexaméthasone) au récepteur des glucocorticoïdes (GR), les GCs régulent l’expression de gènes cibles soit par (i) transactivation par liaison ‘’directe’’ à un élément de liaison à l’ADN de type ‘’(+)GRE’’, (ii) transrépression ‘’directe’’ par liaison à un élément de type ‘’nGRE’’ ou (iii) transrépression ‘’indirecte’’ par interaction physique directe avec des facteurs de transcription pro-inflammatoires tels que AP-1 et NF-κB. Les effets anti-inflammatoires bénéfiques des GCs sont généralement attribués à la transrépression indirecte, alors que nombre de leurs effets secondaires pathologiques indésirables paraissent liés à la transactivation et/ou à la transrépression directe. Notre laboratoire a récemment découvert qu’un composé non-stéroïdien dénommé CpdX ainsi que ses dérivés deutérés, ne présentent ni la fonction de transactivation, ni celle de transrépression directe du GR, tout en stimulant son activité bénéfique de transrépression indirecte. Notre projet a consisté à caractériser un composé non-stéroïdien dit CpdX, ainsi que ses dérivés, quant à leurs activités thérapeutiques et à démontrer qu’elles sont semblables à celles des glucocorticoïdes anti-inflammatoires, couramment utilisés, tout en étant débarrassés de leurs effets pathologiques secondaires, tels que l’ostéoporose, l’atrophie cutanée et le syndrome métabolique. Pour atteindre nos objectifs, nous avons utilisés des modèles de souris présentant soit les affections cutanées (dermatites de contact ou atopique, psoriasis), l'asthme, l’arthrite rhumatismale, la colite ulcérative ou la conjonctivite allergique, associés à des études d’immunologie et de biologie moléculaire et cellulaire. Mon travail de thèse a démontré que CpdX, et certains de ses dérivés deutérés, présentent une activité anti-inflammatoire dans le traitement de ces modèles ‘’souris’’ (Partie I). Nous avons aussi montré que le traitement par CpdX et ses dérivés n’induit pas les effets secondaires pathologiques des glucocorticoïdes (Partie II), ouvrait ainsi la vue à une nouvelle ère dans le traitement à long-terme de maladies inflammatoires, sans provoquer les effets pathologiques indésirables des traitements actuels aux glucocorticoïdes
Upon binding of natural or synthetic glucocorticoids (GCs) (e.g. Dexamethasone) to their glucocorticoid receptor (GR), GCs regulate the expression of target genes either by (i) direct transactivation through direct binding to “(+)GRE” DNA binding sites (DBS), (ii) direct transrepression through binding to “IR nGRE” DBSs or (iii) tethered indirect transrepression mediated through interaction with transactivators, such as NFkB, AP1, or STAT3 bound to their cognate DBSs. The beneficial anti-inflammatory effects of GCs have been generally ascribed to tethered transrepression, whereas many of their long-term undesirable side-effects could be due to transactivation and/or direct transrepression. Our laboratory recently reported that a non-steroidal compound, named CpdX, selectively lacks both direct transactivation and direct transrepression functions, while still exerting an indirect transrepression activity. The goal of our project was to characterize CpdX and some of its derivatives as effective anti-inflammatory drugs similar to glucocorticoids, but lacking their main deleterious side-effects, e.g. osteoporosis, skin atrophy and metabolic disorders. To this end, we have used experimental mouse model for skin disorders (atopic dermatitis, contact dermatitis, and psoriasis), asthma, rheumatoid arthritis, ulcerative colitis and allergic conjunctivitis, combined with immunology, molecular and cellular biology. My thesis studies have demonstrated that in mouse models, CpdX and its derivatives exhibit anti-inflammatory activities, which are similar to those of glucocorticoids (Part I). Importantly, we further show that CpdX and its derivatives do not exhibit the long-term debilitating side-effects of glucocorticoids (Part II). Thereby paving the way to a new era in the long-term therapy of major inflammatory diseases

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48

Bugana, Marco. "Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amslaurea.unibo.it/3529/.

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Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

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Kucher, Kellie Lynn. "Effect of preweanling methylphenidate exposure on the induction, extinction and reinstatement of morphine-Induced conditioned place preference in rats." CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/2892.

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This study examined the effect of preweanling methyphenidate exposure on later drug reward. We examined the induction, extinction, and reinstatement of morphine induced conditioned place preference (CPP) in rats that received methylphenidate pretreatment during the preweanling period.

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Frost, Anna. "Determining the practices and beliefs regarding nutritional supplement use in an urban adult population attending a medical centre in Rondebosch East, Cape Town." Thesis, Stellenbosch : University of Stellenbosch, 2015. http://hdl.handle.net/10019.1/97238.

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Background Empirical research on how and why nutritional supplements (including vitamin/mineral supplements and herbal supplements) are being taken by middle-income populations in South Africa is lacking. This study quantifies the types of nutritional supplements being taken. It unpacks beliefs regarding benefits and risks. This information is useful for healthcare practitioners in similar settings as it could affect their practice of history taking and alert practitioners to the need to know more about nutritional supplement benefits and risks. The information could be used to influence policy regarding advertising and labelling of nutritional supplements. Method The study was a cross-sectional survey. An anonymous self-completed structured questionnaire was completed by 123 participants attending a medical centre during the data collection period. Face-to-face semi-structured interviews were conducted on 16 participants to gather qualitative information. Results Nutritional supplements were widely taken in this questionnaire sample (59%). Consumption was not related to age, language, ethnic group, education and smoking, but nutritional supplements were more commonly used by women and higher income groups. Women who felt they had fair/poor health, women with chronic medical conditions, especially those with depression or women on chronic prescription medication were more likely to take nutritional supplements than those without these characteristics. Wellness, treating tiredness and short-term disease prevention were the most common reasons for taking the supplements, although research proving these benefits is lacking. Chronic disease prevention was an uncommon reason for consumption. Participants were mostly unaware of possible drug interactions and side-effects and therefore felt it unnecessary to inform their practitioner of consumption habits. Conclusion Healthcare professionals should include a nutritional supplement question in their routine history taking, especially when prescribing chronic medication and in the presence of chronic conditions. They should be knowledgeable regarding efficacy, safety, possible side-effects and drug interactions of commonly consumed nutritional supplements in order to advise patients appropriately. Further empirical research is needed into proven benefits of nutritional supplements.

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Dissertations / Theses on the topic 'Side effects of drugs'

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