Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, and, unfortunately, variability exists among pregnant women in the therapeutic effect of anti-emetics as well as in factors that can exacerbate NVP. Identifying and managing these sources of variability will result in significant improvements in the quality of life of pregnant woman. This dissertation addressed clinical pharmacology strategies in managing NVP by focusing on three predominant areas of variability. The first challenge addressed in this dissertation was women with pre-existing gastrointestinal (GI) conditions and adherence and tolerability to prenatal multivitamin supplementation. To identify the role of iron in reducing adherence and increasing NVP and GI symptoms, two separate studies were conducted. In the first study, women randomized to a prenatal multivitamin supplementation with higher iron content experienced more adverse GI effects and increased severity of NVP symptoms. In the second study, after discontinuing iron-containing prenatal multivitamins, two-thirds of women in a prospective cohort reported improvement in their NVP symptoms which was corroborated with validated scales to quantify NVP severity. The second challenge addressed in this dissertation was the effect of heartburn and acid reflux on the severity of NVP. In a controlled, prospective study, women experiencing heartburn and acid reflux experienced greater severity of NVP compared to women with no GI symptoms. Furthermore, treatment of heartburn and acid reflux with acid-reducing pharmacotherapy with associated with a reduction in GI symptoms and NVP severity. Therefore, histamine 2 blockers or proton pump inhibitors, which do not appear to be associated with increased fetal risks, should be administered when required. The third clinical pharmacology challenge addressed in this dissertation was to determine the pharmacokinetic variability of the active ingredients of Diclectin®, first-line pharmacotherapy for the treatment of NVP. Large variability was observed in the area under the curve for both active metabolites: a 6.5-fold difference for pyridoxal-5’-phosphate and a 2.1-fold difference for doxylamine. Whether these pharmacokinetic differences contribute to suboptimal efficacy remains to be determined. In conclusion, based on the results presented in this dissertation, several improvements in clinical pharmacology strategies can be made to enhance management of NVP.

Aim: The aim of this study was to determine whether or not there is evidence for the usage of ginger as an antiemetic in patients experiencing chemotherapy related nausea, based on available scientific literature. Methods: The original articles were found by using search engines PubMed and CINAHL. The selected articles were then analyzed based on their content, quality and results. Based on the results from the content analysis the articles were placed in four different themes. Results: In the first theme two of the articles found that ginger had significant effect on chemotherapy related nausea, when used in combination with regular antiemetic treatment. Two other articles said that it does not. In the second theme four studies found that different forms of ginger lessens nausea, in contrast two other articles found that it does not have any increased effect on said nausea. In the third theme one article found that ginger has significant effect in quelling nausea whilst another article says that it does not show any difference in effect to 5HT3-receptorantagonist metoclopramide. The fourth theme contains one article that find that ginger in combination with high protein diet have antiemetic effect. Conclusions: The conclusion of this literary overview is that there is good evidence that using ginger as an antiemetic in combination with 5HT3-receptor antagonist in patients experiencing chemotherapy related nausea, mainly when given cisplatin.

Despite a rise in breast cancer incidence, mortality rates have fallen. This improvement in mortality is due to the success of anti-cancer treatments such as chemotherapy and radiotherapy. Such treatments, however, are known to be associated with a range of symptoms. A number of studies exploring patients’ chemotherapy-related symptom experiences have shown that patients consistently rate nausea and fatigue highly, not only in relation to severity, but also in relation to the associated distress they experience. The subjective and non-observable nature of both nausea and fatigue complicates their assessment. While a range of assessment tools exists to evaluate patients’ experiences of these two symptoms, there is currently no gold standard assessment tool for assessing either symptom. Moreover, while a range of pharmacological and non-pharmacological interventions have been developed for both symptoms, further evaluation is often needed to provide the level of evidence required to recommend their implementation in real life clinical environments. The SNA↔P (structured nursing assessment into practice) study arose in response to this clinical situation. The SNA↔P study was a longitudinal study that evaluated the impact of a complex evidence-based intervention, incorporating structured multidimensional symptom assessment and multiple symptom management techniques, on patients’ experiences of nausea and fatigue during a course of chemotherapy for breast cancer. Using complementary quantitative and qualitative research methods not only allowed in-depth understanding of patients’ experiences and patterns of nausea and fatigue during a course of chemotherapy, but also facilitated a rounded evaluation of the intervention, incorporating both statistical elements and those of personal significance. The use of these methods showed that the implementation of the SNA↔P intervention in routine clinical practice has significant potential for improving patients’ symptom experiences during a course of chemotherapy. In so doing, it also highlighted a number of areas in which clinical practice can be influenced, and research conducted, to further improve patients’ symptom experiences.

Cannabidiol (CBD), a non-psychoactive cannabinoid found in cannabis suppresses vomiting in shrews (Suncus murinus, Parker et al., 2004), and conditioned gaping in rats (a selective measure of nausea-like behaviour, Parker et al., 2002). CBD‘s anti-emetic/anti-nausea mechanism of action is unknown. However, evidence suggests that CBD may act as a somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptor agonist in the dorsal raphe nucleus (DRN), because the anxiolytic (Campos and Guimaraes, 2008a) and neuroprotectant (Mishima et al., 2005) properties of CBD are 5-HT1A-mediated. Therefore, here we investigated if administration of 5-HT1A receptor antagonists, (WAY100135 or WAY100635) would block CBD‘s anti-emetic/anti-nausea-like effects. Systemic administration of WAY100135 prevented the anti-emetic effect of CBD in shrews, and WAY100135 and WAY100635 attenuated the anti-nausea-like effect of CBD in rats. The effect of CBD on conditioned gaping reactions was most likely the result of its action on somatodendritic 5-HT1A receptors in the DRN, because the anti-nausea-like action of systemic CBD was reversed by intra-DRN administration of WAY100635. As well, when administered into the DRN, CBD suppressed conditioned gaping, an effect that was blocked by systemic WAY100635. In vitro studies revealed that CBD enhanced the ability of 8-OH-DPAT to stimulate [35S]GTPS binding and in vivo studies revealed that systemic subthreshold doses of combined CBD and 8-OH-DPAT synergistically suppressed conditioned gaping. These results suggest that CBD produces its anti-emetic/anti-nausea-like effects by indirect receptor agonism of DRN somatodendritic 5-HT1A autoreceptors. CBD‘s mechanism of action was explored further, by examining its interaction with cannabigerol (CBG), another cannabinoid, which acts in vitro as a 5-HT1A receptor antagonist (Cascio et al., 2010). CBG blocked the systemic CBD-, and 8-OH-DPAT-induced suppression of gaping in rats, as well as the systemic CBD-induced suppression of vomiting in shrews. Therefore, CBG and CBD may be in opposition at the 5-HT1A receptor. These findings shed light on the mechanism of action of non-psychoactive cannabinoids in the cannabis plant, and their effect on nausea and vomiting. These results suggest CBD alone may be an effective treatment in reducing nausea and vomiting. / This research was supported by research grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada to Dr. Parker, a scholarship from NSERC to Erin Rock, and a grant from NIDA to Dr. Mechoulam and Dr. Pertwee.

Bakgrund: Illamående kan uppkomma av många olika orsaker. En av dessa är illamående som uppkommer som en biverkning till cytostatikabehandling. Illamående är en känd biverkning av cytostatikabehandling, varför patienter som ska påbörja och genomgår behandling mot cancer erhåller profylaktisk antiemetikabehandling. Illamående kan få konsekvenser som försämrad nutritionsstatus, elektrolytrubbningar och i vissa fall kan patienten vilja avbryta sin behandling på grund av att illamåendet blir för jobbigt. Trots antiemetika fortsätter illamående att vara ett stort problem vid cytostatikabehandling. Syfte: Att beskriva olika omvårdnadsåtgärder som kan användas som ett komplement till antiemetika vid behandling av illamående orsakat av cytostatika. Metod: En litteraturstudie med grund i analys av kvantitativ forskning genomfördes. Resultat: Sökningar resulterade i fem omvårdnadsåtgärder: progressiv muskelavslappning, tillskott av ingefära, proteintillskott och ingefärskapslar, intag av druvjuice och musikterapi och bildspråk. Alla omvårdnadsåtgärder visade på en effekt på illamåendet i positiv riktning. Dock var resultaten motsägande inom vissa interventioner. Slutsats: Progressiv muskelavslappning, ingefära, druvjuice och musik och bildspråk kan eventuellt, som ett komplement till antiemetika, reducera illamående orsakat av cytostatikabehandling ytterligare. Dock krävs ytterligare forskning inom alla omvårdnadsåtgärder, då befintlig forskning ger otillräckliga eller motsägande resultat. Klinisk betydelse: Då antiemetika inte ger en fullgod effekt mot illamående kan omvårdnadsåtgärder fungera som ett komplement för att minska illamåendet ytterligare. / Background: There are many things that can cause nausea. One of these is chemotherapy. One of the most feared side-effects of chemotherapy is nausea. Untreated, nausea may give rise to consequences such as malnutrition, electrolyte imbalance and in some cases the patient might want to terminate their treatment because the nausea is unbearable. Nausea is a known side-effect to chemotherapy, and patients receive prophylactic antiemetic drugs. Even though patients receive antiemetic drugs, nausea keeps on being a problem while undergoing chemotherapy. Aim: The aim of this study was to describe different nursing interventions which can be used as a complement to antiemetic drugs. Method: A literature review with a basis in quantitative analyses was conducted. Results: Searches resulted in five nursing interventions: progressive muscle relaxation, ginger, protein and ginger, grape juice and music therapy and visual imagery. All of the five nursing interventions pointed towards a positive effect on nausea. But for some interventions contradictory studies were found that wasn’t as positive of the studied intervention. Conclusion: Progressive muscle relaxation, ginger, protein and ginger, grape juice and music therapy and visual imagery, might, as a complement to antiemetic drugs, reduce chemotherapy induced nausea even further than just antiemetic drugs. But more research in this area is needed, while existing research is insufficient. Clinical significance: While antiemetic drugs aren’t sufficient in treating chemotherapy induced nausea, nursing interventions can serve as a complement to reduce nausea even further.

Thesis (M Nursing (Advanced Practice))--University of South Australia, 1995

Thesis (M Nursing (Advanced Practice))--University of South Australia, 1995

Thesis (MA--Art and Design) -- Auckland University of Technology, 2003. / Not all images visible in e-thesis. Also held in print (45 leaves, ill., CD-ROM, 30 cm.) in Wellesley Theses Collection. (T 709.93 CAM)

Thesis (M.S.)--University of Wisconsin-Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 124-130).

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