Introdução: A Doença do Refluxo Gastroesofágico (DRGE) possui elevada prevalência e morbidade. O tratamento clínico consiste em recomendações quanto ao estilo de vida e, essencialmente, no uso de inibidores da bomba protônica (IBP). A aderência (Ad) dos pacientes com DRGE à prescrição, embora fundamental para o sucesso terapêutico, tem sido pouco estudada. Objetivo: Avaliar a Ad ao tratamento com IBP e possíveis variáveis relacionadas em pacientes com DRGE. Métodos: Estudo transversal e prospectivo com 240 pacientes adultos consecutivos com DRGE erosiva e não-erosiva (ne-DRGE) que haviam recebido dose padrão ou dose dobrada de omeprazol em uso contínuo. Todos os pacientes foram classificados conforme o grau, segundo os achados da endoscopia digestiva alta (EDA) em ne-DRGE (162; 67,5%), classificação endoscópica de Los Angeles (LA) A (48; 20,0%), LA B (21; 8,6%), LA C (1; 0,4%), LA D (1; 0,4%) e Barrett (7; 2,9%). Foi aplicado o questionário de Morisky et al constituído de 4 questões com respostas dicotômicas para avaliar a Ad, classificando-a como baixa (0-2 pontos) e alta ad (3-4 pontos). Foi também aplicado o questionário QS-DRGE para a avaliação dos sintomas, com 10 questões com escores de 0 a 50, conforme a frequência menor ou maior dos sintomas. Os resultados de Ad foram relacionados com os dados sócio-demográficos, polifarmácia (PF) (uso de mais de cinco medicamentos diariamente), comorbidades (CM), tempo de tratamento (TT), escore QS-DRGE, presença de sintomas descrita em prontuário, achados da EDA e conhecimento do paciente sobre a doença. Resultados: (1) 126 pacientes (52,5%) apresentaram alta Ad e 114 (47,5%) baixa Ad; (2) Os pacientes mais jovens (p = 0,002) foram menos aderentes; (3) Pacientes sintomáticos de acordo com relato em prontuário apresentaram maior percentual de baixa Ad e 2 vezes maior probabilidade de ter baixa Ad em relação aos assintomáticos (p = 0,02); (4) Os pacientes casados apresentam probabilidade 2,41 vezes maior de ter baixa Ad do que os viúvos. (5) As demais variáveis estudadas não influenciaram a Ad ao tratamento. Conclusões: Pacientes em uso de IBP em tratamento ambulatorial em hospital terciário em São Paulo apresentaram grande percentual de baixa Ad ao tratamento, sendo esta uma possível causa da falha da terapia com IBP. Idade < 60 anos e estado civil casado podem ser fatores de risco para a baixa Ad / Introduction: The Gastroesophageal Reflux Disease (GERD) is a highly prevalent disease and a major cause of morbidity. Clinical treatment is based on lifestyle recommendations and, essentially, in the use of a proton pump inhibitor (PPI). Adherence (Ad) of GERD patients to the prescribed treatment, although critical for therapeutic success, has been little studied. Objective: Assess adherence to the PPI treatment and potential associated variables in patients with GERD. Case studies and Methods: Transversal and prospective study with 240 consecutive adult patients, diagnosed with erosive GERD (e-GERD) and non-erosive GERD (ne-GERD) for whom continuous use of the standard dose or the double dose of omeprazol had been prescribed. Patients were ranked according to the findings of high digestive endoscopy (HDE) in ne-GERD (162; 67.5%); e-GERD: Los Angeles (LA) endoscopic classification A (48; 20.0%), LA B (21; 8.6%), LA C (1; 0.5%), and LA D (1; 0.5%) and Barretts esophagus (7; 2.9%). The Morisky questionnaire, that includes four questions with dicotomic responses to assess Ad, was applied. Ad was classified as low (0-2 points) and high (3-4 points). In addition, the QS-GERD questionnaire was applied to assess symptoms, using 10 questions with score 0 to 50, according to the greater or lesser symptom frequency. Ad results were correlated with personal data (gender and age), demography, polypharmacy (PF), comorbidities (CM), treatment time (TT), QS-GERD scores, symptoms described in the patients record, HDE findings and patient awareness about the disease. Results: (1) 126 patients (52.5%) exhibited high Ad and 114 (47.5%) low Ad; (2) younger patients (p = 0,002) were less compliant; (3) married patients had a 2.41 greater probability to exhibit low Ad as compared to widowers (p = 0.03); (4) patients with symptoms indicated in the patients record exhibited a lower Ad rate and twice greater probability of exhibiting low Ad as compared to asymptomatic patients (p = 0.02); (5) the other variables studied had no influence on treatment adherence. Conclusion: Patients using PPI as out-patients in third care hospital in São Paulo exhibited high rate of reduced treatment adherence, and this may be a potential cause of PPI therapy failure. Age < 60 years and marital status may be risk factors for low adherence

Abstract Aim: The purpose of the study is to show the influence of Proton Pump Inhibitors (PPI in form of esomeprazole) on the bioactivation of dietary nitrate (sodium-nitrate solution) in submaximal exercise, through affecting the gastric pH. Method: Randomized, doubled-blinded, placebo-controlled and crossover study with six subjects (mean ± SD, age 29 ± 5years, height 170 ± 5 centimeters, weight 70 ± 5 Kg, BMI 24,36 ± 1,75 Kg/m2 blood pressure 119/ 77 ± 6 mmHg, 3 male and 3 female). They were tested in two different trials. Every trial consisted of two parts. One part was cycling on 4 different submaximal stages (80W/60RPM, 80W/90RPM, 120W/60RPM, 120W/90RPM) for 5 minutes each, with 90 minutes rest in between. The same protocol was repeated. In the beginning of the resting time a sodium nitrate solution (NaNO3-, 10mg/kg body weight) was ingested. VO2, VCO2, RER, VE, Lactate, Glucose, heart rate and blood pressure were recorded. Venous blood samples were taken. Whether esomeprazole (10mg) or a placebo were taken 24h, 12h and directly before being tested in both trials. Subjects were pleased to have a nitrate poor diet starting when taking the pills. An information sheet was provided. Results: No significant differences were found between the post values and the treatment. Tendencies of a higher oxygen consumption when taking esomeprazole (2,62%) in comparison to placebo (0,11%) were observed. Systolic BP decreased by 3,91% with the placebo while it decreased just 2,04% with esomeprazole after intake. Sex-specific differences occurred in the metabolism of esomeprazole and dietary nitrate. RER showed a significant post nitrate difference between the female and male participants with t=.006 and a significance in predietary nitrate intake. VE in female (40,79 ± 7,20 L/min) and (50,03 ± 10,09 L/min) in male were as well significant (t=.017). Conclusion: Tendencies of effects of PPI are seen in the post-values of VO2 and BP after intake of dietary nitrate. Gender-differences are shown in RER and VE. More research is needed to see the impact of dietary nitrate on the human body under submaximal load.

Introdução: A Doença do Refluxo Gastroesofágico (DRGE) possui elevada prevalência e morbidade. O tratamento clínico consiste em recomendações quanto ao estilo de vida e, essencialmente, no uso de inibidores da bomba protônica (IBP). A aderência (Ad) dos pacientes com DRGE à prescrição, embora fundamental para o sucesso terapêutico, tem sido pouco estudada. Objetivo: Avaliar a Ad ao tratamento com IBP e possíveis variáveis relacionadas em pacientes com DRGE. Métodos: Estudo transversal e prospectivo com 240 pacientes adultos consecutivos com DRGE erosiva e não-erosiva (ne-DRGE) que haviam recebido dose padrão ou dose dobrada de omeprazol em uso contínuo. Todos os pacientes foram classificados conforme o grau, segundo os achados da endoscopia digestiva alta (EDA) em ne-DRGE (162; 67,5%), classificação endoscópica de Los Angeles (LA) A (48; 20,0%), LA B (21; 8,6%), LA C (1; 0,4%), LA D (1; 0,4%) e Barrett (7; 2,9%). Foi aplicado o questionário de Morisky et al constituído de 4 questões com respostas dicotômicas para avaliar a Ad, classificando-a como baixa (0-2 pontos) e alta ad (3-4 pontos). Foi também aplicado o questionário QS-DRGE para a avaliação dos sintomas, com 10 questões com escores de 0 a 50, conforme a frequência menor ou maior dos sintomas. Os resultados de Ad foram relacionados com os dados sócio-demográficos, polifarmácia (PF) (uso de mais de cinco medicamentos diariamente), comorbidades (CM), tempo de tratamento (TT), escore QS-DRGE, presença de sintomas descrita em prontuário, achados da EDA e conhecimento do paciente sobre a doença. Resultados: (1) 126 pacientes (52,5%) apresentaram alta Ad e 114 (47,5%) baixa Ad; (2) Os pacientes mais jovens (p = 0,002) foram menos aderentes; (3) Pacientes sintomáticos de acordo com relato em prontuário apresentaram maior percentual de baixa Ad e 2 vezes maior probabilidade de ter baixa Ad em relação aos assintomáticos (p = 0,02); (4) Os pacientes casados apresentam probabilidade 2,41 vezes maior de ter baixa Ad do que os viúvos. (5) As demais variáveis estudadas não influenciaram a Ad ao tratamento. Conclusões: Pacientes em uso de IBP em tratamento ambulatorial em hospital terciário em São Paulo apresentaram grande percentual de baixa Ad ao tratamento, sendo esta uma possível causa da falha da terapia com IBP. Idade < 60 anos e estado civil casado podem ser fatores de risco para a baixa Ad / Introduction: The Gastroesophageal Reflux Disease (GERD) is a highly prevalent disease and a major cause of morbidity. Clinical treatment is based on lifestyle recommendations and, essentially, in the use of a proton pump inhibitor (PPI). Adherence (Ad) of GERD patients to the prescribed treatment, although critical for therapeutic success, has been little studied. Objective: Assess adherence to the PPI treatment and potential associated variables in patients with GERD. Case studies and Methods: Transversal and prospective study with 240 consecutive adult patients, diagnosed with erosive GERD (e-GERD) and non-erosive GERD (ne-GERD) for whom continuous use of the standard dose or the double dose of omeprazol had been prescribed. Patients were ranked according to the findings of high digestive endoscopy (HDE) in ne-GERD (162; 67.5%); e-GERD: Los Angeles (LA) endoscopic classification A (48; 20.0%), LA B (21; 8.6%), LA C (1; 0.5%), and LA D (1; 0.5%) and Barretts esophagus (7; 2.9%). The Morisky questionnaire, that includes four questions with dicotomic responses to assess Ad, was applied. Ad was classified as low (0-2 points) and high (3-4 points). In addition, the QS-GERD questionnaire was applied to assess symptoms, using 10 questions with score 0 to 50, according to the greater or lesser symptom frequency. Ad results were correlated with personal data (gender and age), demography, polypharmacy (PF), comorbidities (CM), treatment time (TT), QS-GERD scores, symptoms described in the patients record, HDE findings and patient awareness about the disease. Results: (1) 126 patients (52.5%) exhibited high Ad and 114 (47.5%) low Ad; (2) younger patients (p = 0,002) were less compliant; (3) married patients had a 2.41 greater probability to exhibit low Ad as compared to widowers (p = 0.03); (4) patients with symptoms indicated in the patients record exhibited a lower Ad rate and twice greater probability of exhibiting low Ad as compared to asymptomatic patients (p = 0.02); (5) the other variables studied had no influence on treatment adherence. Conclusion: Patients using PPI as out-patients in third care hospital in São Paulo exhibited high rate of reduced treatment adherence, and this may be a potential cause of PPI therapy failure. Age < 60 years and marital status may be risk factors for low adherence

Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota’s composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.

Indiana University-Purdue University Indianapolis (IUPUI) / Fatty acid synthase (FASN) is over-expressed in many cancers, and novel inhibitors that target FASN may find use in the treatment of cancers. It has been shown that orlistat, an FDA approved drug for weight loss, inhibits the thioesterase (TE) of FASN, but can be hydrolyzed by TE. To understand the mechanisms of TE action and for designing better FASN inhibitors, I examined the mechanism of orlistat hydrolysis by TE using molecular dynamics simulations. I found that the hexyl tail of orlistat undergoes a conformational transition, destabilizing a hydrogen bond that forms between orlistat and the active site histidine. A water molecule can then hydrogen bond with histidine and become activated to hydrolyze orlistat. These findings suggest that rational design of inhibitors that block hexyl tail transition may lead to a more potent TE inhibitor. To search for novel inhibitors of TE, I performed virtual DOCK screening of FDA approved drugs followed by a fluorogenic assay using recombinant TE protein and found that proton pump inhibitors (PPIs) can competitively inhibit TE. PPIs, which are used for the treatment of gastroesophageal reflux and peptic ulcers, work to decrease gastric acid production by binding irreversibly with gastric hydrogen potassium ATPase in the stomach. Recently, PPIs have been reported to reduce drug resistance in cancer cells when used in combination with chemotherapeutics, although the mechanism of resistance reduction is unknown. Further investigation showed that PPIs are able to decrease FASN activity and cancer cell proliferation in a dose-dependent manner. These findings provide new evidence that FDA approved PPIs may synergistically suppress cancer cells by inhibiting TE of FASN and suggests that the use of PPIs in combinational therapies for the treatment of many types of cancer, including pancreatic cancer, warrants further investigation.

No description available.

Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.

Acid-related disorders are common, chronic conditions that have considerable impact on a patient's quality of life. In a study conducted by Majumdar et al. (2003:2411) the prevalence of chronic acid-related disorders was 2.3%. Acid-related disorders represent a major financial consideration with respect to the costs of drug prescribing (Whitaker, 1998:6). Health care cost increases each year. This leads to an increased interest in economic evaluation of health care and medical technologies (Anell & Svarvar, 2000:175). Health care providers no longer make treatment decisions independent of the consideration of the resultant cost. The treatment provided must not only provide value but the value must be documented to justify spending money. Economic evaluation research has emerged to offer guidance to policy makers, practitioners, health plans and institutions facing difficult treatment and coverage decisions (Ellis era/., 2002:271). The main objectives of this study were to investigate the prescribing patterns and cost of acid reducing medicine with special reference to proton pump inhibitors and histamine-2 receptor antagonists in a section of the private health care sector of South Africa from 2001 to 2006. A longitudinal retrospective drug utilisation study was done on acid reducing medicine items claimed through a national medicine claims database. The five study years were 2001, 2002, 2004, 2005 and 2006. All the study years stretched from 1 January to 31 December. It was determined that acid reducing medicine items prescribed decreased from 2.74% during 2001 to 2.50% during 2006 of all medicine items claimed. The same decreasing trend was observed regarding the cost of acid reducing medicine items. The cost percentage decreased from 4.89% (2001) to 3.72% (2006). However, the average cost per medicine item for the acid reducers increased by 5.35% from 2001 (R230.04 ± 176.29) to 2002 (R243.72 ± 184.18) and then decreased by 15.23% from 2002 to 2004. It again decreased with 15.05% from 2004 (R206.19 ± 179.42) to 2006 (R175.70 ± 172.55). The changes in the average cost of acid reducers were of no practical significance. Proton pump inhibitors represented about half of the acid reducing medicine items prescribed and more than 70% of the total cost of acid reducing medicine items during the study years. The average cost of PPIs revealed a practical significant decrease (d > 0.8) from 2002 (R372.42 ± 156.62) to 2006 (R241.56 ± 177.21). H2RAs contributed between 15.00% and 18.26% of all acid reducing medicine items while contributing to between 9.68% and 16.85% of the total cost of all acid reducers. The active ingredient most often prescribed was lansoprazole during 2001 and 2002, esomeprazole during 2004 and omeprazole during 2005 and 2006. Lanzor® 30mg was the acid reducer with the highest cost from 2001 to 2005, while Pariet® 20mg took the lead in 2006. Zantac® 150mg effervescent tablets were the H2RA, with the highest cost, during the five study years. The percentage innovator items decreased by 4.50% from 2001 to 2002, increased by 1.01% from 2002 to 2004 and decreased again by 31.06% from 2004 to 2006. The slight increase in the percentage innovator medicine items claimed from 2002 to 2004 may be explained by the introduction of Nexiam® (esomeprazole) into the market in 2002. The total number of generic medicine items claimed contributed between 9.62% (n = R1 788 242.25) in 2001 and 30.75% (n = R3 196 163.34) in 2006 of the total cost of acid reducing medicine items. The average cost per day of innovator medicine items was higher than the average cost per day of generic medicine items. This might be explained by a lower average cost for generic medicine items. It was also determined that the prevalence of the two-drug regimens was the highest during the five study years. The Helicobacter pylori (H.pylori) eradication treatments, which included different antibiotics, increased from 2.72% in 2001 to 5.05% in 2006. The PDD for most of the active ingredients of H2RAs and PPIs remained stable during the study years. However, it appears that the PDDs, of the PPIs, active ingredients were more constant than the PDDs, or the H2RAs, active ingredients. The median of the different PPI active ingredients was reasonably more constant than the median of the different H2RA active ingredients. Thus the changes between the PPIs' and H2RAs' active ingredients might be explained by the variation in the median (the number of days the relevant medicine item was claimed for). It is then also recommended that the aspects of generic substitution as well as the usage of H2RAs as prescribed vs. self medication should be further investigated to increase possible cost savings. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.

Acid-related disorders are common, chronic conditions that have considerable impact on a patient's quality of life. In a study conducted by Majumdar et al. (2003:2411) the prevalence of chronic acid-related disorders was 2.3%. Acid-related disorders represent a major financial consideration with respect to the costs of drug prescribing (Whitaker, 1998:6). Health care cost increases each year. This leads to an increased interest in economic evaluation of health care and medical technologies (Anell & Svarvar, 2000:175). Health care providers no longer make treatment decisions independent of the consideration of the resultant cost. The treatment provided must not only provide value but the value must be documented to justify spending money. Economic evaluation research has emerged to offer guidance to policy makers, practitioners, health plans and institutions facing difficult treatment and coverage decisions (Ellis era/., 2002:271). The main objectives of this study were to investigate the prescribing patterns and cost of acid reducing medicine with special reference to proton pump inhibitors and histamine-2 receptor antagonists in a section of the private health care sector of South Africa from 2001 to 2006. A longitudinal retrospective drug utilisation study was done on acid reducing medicine items claimed through a national medicine claims database. The five study years were 2001, 2002, 2004, 2005 and 2006. All the study years stretched from 1 January to 31 December. It was determined that acid reducing medicine items prescribed decreased from 2.74% during 2001 to 2.50% during 2006 of all medicine items claimed. The same decreasing trend was observed regarding the cost of acid reducing medicine items. The cost percentage decreased from 4.89% (2001) to 3.72% (2006). However, the average cost per medicine item for the acid reducers increased by 5.35% from 2001 (R230.04 ± 176.29) to 2002 (R243.72 ± 184.18) and then decreased by 15.23% from 2002 to 2004. It again decreased with 15.05% from 2004 (R206.19 ± 179.42) to 2006 (R175.70 ± 172.55). The changes in the average cost of acid reducers were of no practical significance. Proton pump inhibitors represented about half of the acid reducing medicine items prescribed and more than 70% of the total cost of acid reducing medicine items during the study years. The average cost of PPIs revealed a practical significant decrease (d > 0.8) from 2002 (R372.42 ± 156.62) to 2006 (R241.56 ± 177.21). H2RAs contributed between 15.00% and 18.26% of all acid reducing medicine items while contributing to between 9.68% and 16.85% of the total cost of all acid reducers. The active ingredient most often prescribed was lansoprazole during 2001 and 2002, esomeprazole during 2004 and omeprazole during 2005 and 2006. Lanzor® 30mg was the acid reducer with the highest cost from 2001 to 2005, while Pariet® 20mg took the lead in 2006. Zantac® 150mg effervescent tablets were the H2RA, with the highest cost, during the five study years. The percentage innovator items decreased by 4.50% from 2001 to 2002, increased by 1.01% from 2002 to 2004 and decreased again by 31.06% from 2004 to 2006. The slight increase in the percentage innovator medicine items claimed from 2002 to 2004 may be explained by the introduction of Nexiam® (esomeprazole) into the market in 2002. The total number of generic medicine items claimed contributed between 9.62% (n = R1 788 242.25) in 2001 and 30.75% (n = R3 196 163.34) in 2006 of the total cost of acid reducing medicine items. The average cost per day of innovator medicine items was higher than the average cost per day of generic medicine items. This might be explained by a lower average cost for generic medicine items. It was also determined that the prevalence of the two-drug regimens was the highest during the five study years. The Helicobacter pylori (H.pylori) eradication treatments, which included different antibiotics, increased from 2.72% in 2001 to 5.05% in 2006. The PDD for most of the active ingredients of H2RAs and PPIs remained stable during the study years. However, it appears that the PDDs, of the PPIs, active ingredients were more constant than the PDDs, or the H2RAs, active ingredients. The median of the different PPI active ingredients was reasonably more constant than the median of the different H2RA active ingredients. Thus the changes between the PPIs' and H2RAs' active ingredients might be explained by the variation in the median (the number of days the relevant medicine item was claimed for). It is then also recommended that the aspects of generic substitution as well as the usage of H2RAs as prescribed vs. self medication should be further investigated to increase possible cost savings. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2008.