In Primary Aldosteronism (PAL) excessive amounts of aldosterone cause sodium and water retention and, in many individuals, this leads to moderate to severely high blood pressure. Although the chemistry and physiology are increasingly well understood, including the outcomes of treatment on physical health, there has been no systematic study of the psychological dimension of PAL. Anecdotally, patients exhibit symptoms such as angry outbursts, irritability, anxiety and defensiveness, and partners of these patients sometimes mention poor anger control and brittle or unpredictable moods. This thesis reports a systematic study of anger and anxiety among patients undergoing treatment for PAL. Eighty-three patients were recruited over an 11-month period to a prospective, pre-post design study to determine if treatment was associated with change in psychological state. Participants completed the State-Trait Anger Expression Inventory (STAXI-2), State-Trait Anxiety Inventory (STAI) and Psychosocial Adjustment to Illness Scale (PAIS) questionnaires. Adrenal Vein Sampling confirmed overproduction of aldosterone in one or both adrenal glands. Patients with Aldosterone Producing Adenoma (APA) were offered adrenalectomy. As per usual treatment protocols, patients with Bilateral Adrenal Hyperplasia (BAH) were prescribed spironolactone or amiloride depending predominantly on severity of blood pressure and potassium levels. Post-test questionnaires were completed after 6-8 months. Analysis was by mixed design (between-within subjects) ANOVA. Participant numbers in the adrenalectomy group fell far short of expectations. Fourteen past patients who had undergone unilateral adrenalectomy completed a retrospective semi-structured questionnaire. This qualitative data was analysed to identify themes similar to quantitative data. At baseline, 'non-completers' (ie those who did not complete the post-test; n=19), were significantly more angry than 'completers' (n=50) in State Anger (p< .01), Trait Anger (p< .05) and Anger Expression Index (p< .001). Trait Anxiety was also higher (p< .05), as was Psychological Distress (p< .05). Among those who participated at both interviews, there was small but statistically significant adverse treatment effect with higher scores for State Anger (p< .05), and Feeling Angry (p< .05). However for Trait Anger (p< .01), and 2 of its 3 sub-scales Angry Temperament (p< .05) and Angry Reaction (p< .01) there was a slight to moderate decrease in negative affect with treatment. Psychological Distress scores also improved (p< .05). Across all ANOVAs, there were no significant interaction effects, suggesting that any treatment effect was equivalent for the two drugs. Qualitatively collected data elucidated participants' changes in approach to life and relationships since adrenalectomy. Themes that emerged in the data included improved ability to cope with external stress, better control of emotions, more relaxed relationships and attitude to work, and a greater vitality and quality of life. Generally the comments were consistent with the drug treatments; there was noticeable benefit, including perceived better anger control and less anxiety. Positive psychological effects of treatment observed in the two drug groups were triangulated with data from a qualitative study. The combined evidence suggests that when excess circulating aldosterone is reduced (adrenalectomy), or blocked (spironolactone), or aldosterone's salt and water retaining effects are minimised (amiloride), then nervous irritability and its subsequent psycho-behavioural manifestations are reduced. The effect however is slight and the conclusions are weakened by an apparent attrition bias, and the absence of a control group. Implications for further research are discussed.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-03-23T19:00:13Z No. of bitstreams: 1 Peçanha, Bruna Rachel de Britto [Dissertação, 2012].pdf: 3907379 bytes, checksum: f2acabc3c1c39363b86f0d651d6b5936 (MD5) / Made available in DSpace on 2017-03-23T19:00:13Z (GMT). No. of bitstreams: 1 Peçanha, Bruna Rachel de Britto [Dissertação, 2012].pdf: 3907379 bytes, checksum: f2acabc3c1c39363b86f0d651d6b5936 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Polímeros de impressão molecular (MIPs) foram sintetizados e aplicados como adsorventes na técnica de extração em fase sólida (EFS). O método de polimerização por precipitação foi utilizado para a síntese dos polímeros, devido à simplicidade de preparo, altos rendimentos e obtenção de partículas mais uniformes, devido a não trituração do polímero. O MIP foi sintetizado com ácido metacrílico (MAA) como monômero funcional, trimetacrilato de trimetilolpropano (TRIM) e dimetacrilato de etilenoglicol (EDMA) como agentes de reticulação e o cloridrato de amilorida (AMI) foi escolhido como molécula-molde. Diferentes proporções de MAA, TRIM, EDMA, volume e tipo de solvente foram utilizadas para ajuste das condições ideais de síntese. Os MIP foram avaliados quanto à capacidade de adsorção comparando-se a polímeros sintetizados na ausência da molécula-molde (NIP, polímeros não impressos). O solvente de elevada polaridade empregado na síntese (THF:MeOH:H2O) permitiu o emprego da técnica para moléculas polares como AMI. O controle no volume de solvente permitiu a obtenção de partículas maiores, de modo que a EFS foi realizada em condições usuais, o que confere um potencial para aplicação dessa técnica de polimerização na preparação de adsorventes para EFS. O polímero que apresentou maior capacidade adsortiva no ensaio realizado em tampão citrato-acetato pH 6,5 foi o MIP/NIP 12 (AMI:MAA:TRIM 1:8:10), com uma taxa média de adsorção de 83 e 88% para NIP e MIP, respectivamente. A adsorção foi elevada devido a interação iônica entre MAA e AMI promovida pelo controle de pH, porém foi não específica. O polímero MIP/NIP 12 foi aplicado como adsorvente na EFS, onde a recuperação de AMI foi avaliada nos resíduos de carregamento e eluição com solventes. O carregamento com tampão citrato-acetato pH 6,5 foi o ideal, favorecendo a interação iônica do polímero com o analito. A eluição total de AMI do cartucho somente ocorre após lavagem com o solvente na presença de ácido, que protona os grupos carboxila do polímero, rompendo assim a interação iônica com o analito / Molecularly imprinted polymers (MIPs) were synthesized and applied as adsorbents in solid-phase extraction technique (SPE). The polymers have been synthesized by precipitation polymerization method because of its simplicity, high yields and good control of final size and shape of particles. MIP was synthesized using methacrylic acid (MAA) as functional monomer, trimethylolpropane trimethacrylate (TRIM) and ethyleneglycol dimethacrylate (EDMA) as cross-linker and amiloride hydrochloride (AMI) was chosen as template. Different ratios of MAA, TRIM and EDMA, volume and type of solvent were used to adjust the optimal synthesis conditions. The MIP were tested for adsorption capacity compared to the polymers synthesized in the absence of template molecule (NIP, non-imprinted polymers). The polar solvent mixture used (THF:MeOH:H2O) allowed the synthesis of MIP of polar molecules as AMI. The solvent volume control afforded the larger particles so the SPE was performed in the usual conditions, giving a potential application for this polymerization technique in the preparation of adsorbents for SPE. The polymers with higher adsorption capacity at the test performed in citrateacetate buffer pH 6,5 was MIP/NIP 12 (AMI:MAA:TRIM 1:8:10) with adsorption rate of 83 and 88% for NIP and MIP, respectively. The recognition of MIP was due to ionic interaction between MAA and AMI promoted by pH control, but was not specific. The polymer MIP/NIP 12 was used as a solid-phase extraction sorbent and the recoveries of AMI was evaluated using different loading and elution conditions. The loading with buffer citrate-acetate pH 6,5 was optimal, due to ionic interaction of the polymer with the analyte. Total elution of AMI bound to the polymers only occurs after washing with a acid-containing solvent, because of protonation of the carboxyl groups of the polymer and disrupting the ionic interaction with the analyte