Bakgrund Intresse för användning av geler i läkemedelsindustrin har ökat de senaste åren. Geler kan fungera som läkemedelsbärare och därmed skydda känsliga läkemedel från nedbrytning. De kan också användas som system för kontrollerad frisättning. För att kunna tillverka säkra och effektiva läkemedel är det viktigt att förstå självaggregeringsegenskaper. Syftet med denna studie var att studera självaggregeringsegenskaper hos en katjonisk amfifila ämne, amitriptylinhydroklorid (AMT), i polyakrylat makrogeler med lågvinkelröntgenspridning (SAXS) vid två olika jonstyrkor samt att beräkna aggregationstalet med hjälp av SAXS och fluorescenslivslängdsmätning.  Metod Beredning av makrogeler och buffert utfördes enligt tidigare studier därefter tillsattes AMT och gelen fick jämviktas före analysen med SAXS. Pyren och 3,4-dimetylbenzofenon användes för fluorescensanalys.  Resultat Gelens volym minskade med ökad AMT-koncentration och en skal/kärna-fasseparation kunde tydligt observeras i 10 mM buffert. SAXS-resultatet visade oordnade fasstruktur och det genomsnittliga aggregationstalet i denna studie var ca 50.  Diskussion och Slutsats Det är oväntat att AMT inte bildar ordnad faser vid riktigt hög koncentration, vilket betyder fler studier med olika metoder behövs göras i framtiden. Däremot ses en systematisk förändring med ökad AMT-koncentration. Det genomsnittliga aggregationstalet innebär att miceller är inte helt sfäriska. En oordnad fasstruktur kan förklara dynamiken för omorganisationen av AMT i geler är snabbare än för vanliga tensider, vilket är av betydelse för läkemedlets frisättnings kinetik.

Irritable bowel syndrome (IBS) är en av de vanligaste diagnostiserade GI-tillstånden idag och är en störning av gastrointestinalkanalen (GI-kanalen). Det finns inget botemedel mot IBS på grund av att patogenesen är oklar och därför är fokusen symtomlindring vid behandling.  De vanligaste symtom som förekommer är buksmärta, obehag i buk, uppblåsthet, utspänd buk och förändring av avföringens konsistens och frekvens. Patofysiologin är inte fullt klarlagd men en rubbning i tarm-hjärn-axeln kan leda till förändring i GI-rörelser. Neurotransmittorerna noradrenalin och serotonin (5-HT) är troligen viktiga faktorer för patofysiologin kopplad till tarm-hjärn-axeln. Syftet var att undersöka effektiviteten och säkerheten för de antidepressiva läkemedlen vid behandling av IBS. De antidepressiva som undersöktes i arbetet var tianeptin, amitriptylin, escitalopram, venlafaxin, vortioxetin och mirtazapin. De fem artiklarna som användes i detta arbete upptäcktes med hjälp av databaserna Pubmed och Onesearch. Sökord som användes var ”IBS” AND ”antidepressants” och ”IBS” AND ”SSRI”.  Alla antidepressiva visade en signifikant förbättring för livskvalitén hos deltagarna i studierna. Tianeptin, amitriptylin, escitalopram, venlafaxin och mirtazapin undersökte förändring av buksmärta och alla hade en signifikant förbättring förutom escitalopram. Escitalopram jämfördes mot rektal ballongutvidgning vid behandling hos IBS med förstoppning (IBS-C). Ballongutvidgningen visade bättre resultat än escitalopram och denna jämförelse gör det svårt att dra någon slutsats om escitalopram i arbetet. Amitriptylin, tianeptin och mirtazapin undersökte förändring av avföringskonsistensesn och frekvensen och visade en signifikant förbättring hos IBS med diarré (IBS-D). Venlafaxin visade signifikant förbättring för både lös och hård avföringsfrekvens och studerade ingen specifik IBS-grupp. Vortioxetin undersökte alla IBS-grupper och endast förändring av livskvalitén, depression och ångest vilket också gör det svårt att dra slutsats om effekt hos IBS. Det var inga av de depressiva medlen som gav allvarliga biverkningar, dock kan vissa biverkningar tolkas som mer obehagliga än andra. För vissa antidepressiva var det deltagare som avslutade studien på grund av biverkningar. Amitriptylin, tianeptin, venlafaxin vortioxetin och mirtazapin visade alla god effekt och säkerhet. Om effektiviteten ock säkerheten jämförs bland dessa har tianeptin det bästa resultatet. / Irritable bowel syndrome (IBS) is one of the most diagnosed conditions in the gastrointestinal (GI) tract today and is a disorder of the GI tract. There is no cure for IBS, which is probably due to the fact that the pathogenesis is unclear, and therefore the focus has been a symptom-relieving treatment. The most common symptoms that occur are abdominal pain, abdominal discomfort, bloating, distension of the abdomen, and change in the consistency and frequency of the stool. The pathophysiology is not fully understood, but a disorder of the gut-brain axis can lead to a change in GI movements. The neurotransmitters norepinephrine and serotonin (5-HT) are probably important factors for pathophysiology and linked to the gut-brain axis.  The aim was to investigate the effectiveness and safety of antidepressants used in IBS treatment. The antidepressants examined in this literature were tianeptine, amitriptyline, escitalopram, venlafaxine, vortioxetine, and mirtazapine. The five articles on which current litter tour work is based were obtained using the PubMed and OneSearch databases. Keywords used were "IBS" AND "antidepressants" and "IBS" AND "SSRI."  All the antidepressants examined showed a significant improvement in the participants' quality of life in the studies. The studies also examined changes in abdominal pain using tianeptine, amitriptyline, escitalopram, venlafaxine, and mirtazapine. All participants showed a significant improvement and reduced abdominal pain except when ingesting escitalopram. Intake of escitalopram was compared against rectal balloon enlargement as a treatment for IBS with constipation (IBS-C). The balloon expansion showed better results than escitalopram, and this comparison makes it difficult to draw any conclusion about escitalopram and its actual effect in different types of IBS. Amitriptyline, tianeptine, and mirtazapine investigated stool consistency and stool frequency changes and showed a significant improvement in these symptoms in IBS with diarrhea (IBS-D). Venlafaxine showed significant improvement for both loose and hard stool frequency; however, no specific IBS group was studied in this study. When ingesting vortioxetine, all different IBS groups and changes in quality of life, depression, and anxiety were examined, making it difficult to conclude about the effect of the drug in IBS. None of the antidepressant medicines produced severe side effects. However, some side effects can be interpreted as more unpleasant than others, and hence there was some loss during some studies.  Amitriptyline, tianeptine, venlafaxine vortioxetine, and mirtazapine showed good efficacy and safety. If the effectiveness and safety were to be compared between these drugs, tianeptine would be the first choice in treating IBS.

Background: Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Methods: Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. results: Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. conclusion: Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.

Background: Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Methods: Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. results: Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. conclusion: Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients’ comorbidities and co-medication.