STUDENTSKÁ VĚDECKÁ KONFERENCE

Zuzana Kubiszová ¹, Miriama Chmúriková ¹, Jiří Zeman ¹, Sylvie Pavloková ¹, David Vetchý ¹, Zdeněk Moravec ², Lukáš Matějovský ³

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, Masaryk University
² Department of Chemistry, Faculty of Science, Masaryk University
³ Oritest Ltd., Prague, Czech Republic

Keywords: lyophilization, pellets, metasilicate, porosity, detection tube

Introduction

Due to the escalation of international military tensions, chemical warfare agents (CWAs) are once again becoming a major threat. Rapid detection of their presence in air or water, even in extremely low concentrations, is an essential part of safety precautions. Detection tubes (DTs) are a commonly used type of chemosensor and the development of their innovative second-generation involves the search for suitable highly porous carriers with a high specific surface area. Such carriers should more effectively adsorb detection reagents and CWAs, which should lead to an overall improvement in sensitivity and detection rate.

Methods

This study aimed to prepare highly porous carriers in form of pellets using lyophilization as a drying method. Initially, different process parameters were tested to optimize the lyophilization process. In addition, a highly porous material – magnesium aluminometasilicate (Neusilin^® US2) was utilized in increasing concentrations. The physicochemical properties of prepared batches were evaluated. The most important aspect – the specific surface area was measured by the Brunauer-Emmett-Teller (BET) method. Selected samples were provided to the Oritest Ltd. company, where these pellets were impregnated with the detection reagent o-phenylenediamine-pyronine and tested for the presence of phosgene/diphosgene.

Results

Lyophilization was found to be an efficient method to prepare highly porous pellets. Freezing of the pellets at −30 °C or −80 °C without additional heating of the lyophilizer shelves during lyophilization was evaluated as the most suitable condition. Pellets containing Neusilin^® US2 had better physicochemical properties than samples without metasilicate. The highest specific surface area was measured in pellets containing 50 % (w/w) of Neusilin^® US2. On the one hand, the mechanical resistance of the pellets decreased with increasing metasilicate concentration, on the other hand, the color change during detection was more pronounced.

Conclusions

In conclusion, all batches of pellets containing Neusilin^® US2 showed potential to be used as the carriers in DTs or prospectively as carriers for active substances in modern dosage forms.

Acknowledgment: The study was supported by the Security Research Program of the Ministry of the Interior of the Czech Republic, no. VI20192022172.

Supervisors: PharmDr. Jiří Zeman, Ph.D., prof. PharmDr. Mgr. David Vetchý, Ph.D.

Radka Slavíčková ¹, Dana Mazánková ¹

¹ Department of Applied Pharmacy, Faculty of Pharmacy, Masaryk University

Key words: analgesics, coanalgesics, medical cannabis, chronic pain, sleep quality, Pittsburgh sleep quality index, sleep record, sleep diary

Background and Aims

Chronic pain is still an underestimated disease despite a wide range of available analgesic therapies. The research aimed to evaluate the effect of analgesic treatment on the quality of sleep and its development in patients with chronic pain.

Methods

A total of 34 patients with chronic pain were included in the research. The source of data was the Department of Pain Treatment, University Hospital Brno. Based on pharmacotherapy, patients were divided into two groups, which were compared with each other (Group 1: patients using analgesics or co-analgesics, Group 2: patients using medical cannabis alone or in combination with analgesics or co-analgesics). Medical cannabis was prescribed to patients in different proportions of THC (tetrahydrocannabinol) and CBD (cannabidiol) – THC in the ratio of 6–8.7% and CBD in the ratio of 6.2–8.7%. The evaluation was performed according to the internationally recognized questionnaire PSQI – Pittsburgh Sleep Quality Index; all 7 components were evaluated. The next part of the evaluation was based on two prepared documents: Sleep record and Sleep diary. Evaluation of sleep quality development took place in three-time intervals; evaluated parameters were: sleep efficiency, feelings after waking up, subjective evaluation of sleep, evaluation of the effect of caffeinated beverages on sleep quality, influence of physical activity on sleep, general wakefulness during the day and pain according to VAS (Visual Analog Scale). Statistical evaluation of PSQI was performed using Pearson's Χ² good agreement test and Student's two-sample t-test.

Results

The average outcome value of sleep efficiency in patients with analgesics was 74.04% and in patients with medical cannabis 74.33%. The statistical analysis did not show a significant difference between the evaluated groups. However, based on the evaluation of sleep records and diaries, there was a significant improvement in sleep efficiency in patients with analgesics – by almost 9%, compared to patients with medical cannabis, where this value was practically stable throughout. The change in pharmacotherapy (transition from conventional analgesic to opioid treatment, transition from weak opioids to strong opioids, increase in analgesic therapy or addition of infusion therapy) had a positive effect on sleep efficiency in patients taking analgesics – there was an improvement from 85.12% to 93.83%. Improvement was also seen in both waking sensations (from 2.2 to 1.5) and overall wakefulness during the day (from 2.6 to 2.75). Positive changes were also noted in the subjective evaluation of sleep (improvement from 3.3 to 4.25). At the same time, the pain was reduced from the original value of 5.9 to 4.5 (evaluated according to VAS). This fact was also reflected in the increased mobility of patients – patients ranged on average 60–120 minutes a day. Patients consumed an average of 2 cups of coffee per day throughout the survey. There were no significant changes in patients using medical cannabis. The sleep efficiency value did not differ much – 84.78% in the first phase, 82.98% in the second phase, and in the third phase, there was a slight improvement to 84.95% in a small group of patients. Patients also rated their sleep (2.5) and their alertness during the day (on average 1.8). There was a positive change in feelings after waking up from 2.6 to 2.2, which means that patients feel sleepy rather than tired. Patient mobility varied, with some less than 30 minutes of exercise daily, others up to 2 hours. Cannabis patients drink an average of 1 cup of coffee a day.

Conslusions

We can see that changing analgesic pharmacotherapy in Group 1 – whether switching from conventional analgesic treatment to opioids or increasing current therapy – has had a positive effect not only on the quality of sleep but also on reducing patient pain. During the research, there were no major differences in Group 2 in patients with medical cannabis.

Author's CV: Radka Slavíčková is completing master's degree program Pharmacy at the Faculty of Pharmacy of Masaryk University.

Supervisor: PharmDr. Bc. Dana Mazánková, Ph.D.

Jana Mečiaková  ¹, Dana Mazánková ¹

¹ Department of Applied Pharmacy, Faculty of Pharmacy, Masaryk University

Key words: effective communication, dispensing minimum, cross-selling, up-selling,
down-selling

Background and Aims

The diploma thesis deals with methods leading to increased patient compliance with treatment, which can be supported by using effective communication, managing patient objections, providing a dispensing minimum, and the correct application of sales techniques in pharmacy. In this way, the maximum effect of pharmacotherapy can be achieved. This thesis aimed to process dispensing minima and suitable sales techniques (up-selling,
cross-selling, down-selling) for selected nine active substances, which are grouped thematically into four groups.

Methods

The active substances were selected according to their frequency of deliveries to pharmacies in the Czech Republic in the fourth quadrant in 2020. The first group consisted of rosuvastatin and atorvastatin, the second group consisted of acetylsalicylic acid, the third group consisted of ramipril, perindopril, amlodipine, telmisartan and furosemide in the treatment of arterial hypertension, the fourth group consisted of omeprazole. The structure of the processed dispensing minimum includes the following information: registered medicinal products containing the given active substance in the Czech Republic, dosage, explanation of drug effect and basic indications, side effects, interactions with other drugs, food or beverages, expected duration of treatment, proper storage of drugs, other recommendations for the patient. Only the cross-selling technique is processed within the sales techniques for prescription-only medicine. Cross-selling, up-selling and down-selling techniques are processed for over-the-counter (OTC) medicines.

Results

Omeprazole was chosen to present the results of this thesis. This substance is on the market in the Czech Republic available both as a prescription medicine and as an OTC medicine. Thus, all three sales techniques (cross-selling, up-selling and down-selling) can be presented. Within cross-selling, it is possible to recommend using antacids (in case of difficulties maximum for 3 days after starting omeprazole therapy), vitamin B12 (reduced blood levels of vitamin B12 due to hypochlorhydria may cause hematopoietic or nervous system disorders, dosage 25–1000 mg per day), calcium (reduced blood levels of calcium due to hypochlorhydria may increase the risk of fractures, dosage 1000 mg per day) or magnesium (reduced blood levels of magnesium due to hypochlorhydria may cause for example fatigue of muscle cramps, dosage 250–400 mg per day). The use of professional up-selling is explained by the dispensing of a product containing another active substance with a lower interaction potential (pantoprazole). The economic up-selling is explained by the dispensing of a larger package of the product. Down-selling is presented in the example of dispensing a cheaper generic drug or a cheaper product containing another active substance (e.g. famotidine).

Conclusions

Sales techniques should primarily maximize the effect of pharmacotherapy because the patient can benefit from a suitably chosen product (for example, by shortening the duration of treatment or alleviating difficulties). Effective communication should be used throughout the communication process to support the effect of pharmacotherapy and increase patient compliance. Thanks to effective communication, the pharmacist can choose a suitable product for the patient´s specific problems and improve his adherence to treatment and thus the effectiveness of pharmacotherapy.

Author's CV: Jana Mečiaková, a fifth-year student at the Faculty of Pharmacy of Masaryk University.

Supervisor: PharmDr. Bc. Dana Mazánková, Ph.D.

Eva Federičová ¹

¹ Department of Applied Pharmacy, Faculty of Pharmacy, Masaryk University

Key words: marketing communication, pharmacy, advertisement on over-the-counter medicines, questionnaire

Background and aims:

The main role of advertisement with other marketing tools in pharmacy is to satisfy patients' needs by increasing product sales. This work aimed to find out the ability of advertisements to bring new data about OTC (over-the-counter) medicines to pharmacists and pharmacy assistants and the effect of advertisements on dispensing these medicines.

Methods:

To obtain the data, an anonymous questionnaire was created on the website Survio for a period of 4 months, from July 2021 to October 2021. A questionnaire was distributed by e-mail address to 2678 pharmacies in the Czech Republic, which were published on the website named SÚKL. The questionnaire contained 30 questions; respondents were pharmacists and pharmacist assistants. Questions found out basic demographic information, OTC advertisement as the source of information, conscious and unconscious effect on respondents, and how advertisements on OTC affect later respondents' manners. Six hypotheses were made from acquired data, which were tested by the statistical χ2 test of independence (α=0.05).

Results:

The total number of evaluated questionnaires was 584. The questionnaire survey proved that the advertisement on OTC is not a reliable source of information for 69% of respondents. The respondents can't find the information they need in OTC advertisements (89,6%) because it does not provide them. Information presented in advertisements on OTC drugs isn't synoptical, graspable, and content enough, according to 85,1% of respondents. Advertisement on OTC is perceived as confusing and making a mess in reclaimed information (68,5%). Although the majority of respondents don't consider an advertisement as a reliable source of information, advertisements inform respondents about the existence of the drug, but they are looking for more detailed information from different sources later (91%). Different types of advertisement platforms were evaluated within the reliability of advertisement. There was a best-placed advertisement in the professional press, which was marked with the highest level of reliability (79,5% respondents). The second part of the questionnaire examines advertisements' conscious and unconscious effects on respondents. According to obtain data, advertisement isn't a factor in reconsidering dispensing OTC drugs (89,2%), and 72,6% of respondents don't recommend OTC drugs due to the lower price mentioned in the advertisement. In comparing the credibility of the advertised OTC drug with the not promoted OTC drug, respondents don't consider advertised OTC drug for more trustworthy (89%). The last part of the questionnaire survey analyzed the effect of advertisement on later respondents' manners. Respondents recognize the higher interest of patients for OTC drugs promoted by advertisement in 89%. Respondents don't prefer dispensing OTC drugs because is a higher chance of good patient compliance (76,7%), and according to 67,1% of respondents, advertisements contribute to a higher amount of drug interactions. According to the results, we can say that, in general, advertisements on OTC drugs contribute to higher patients' knowledge about OTC drugs (72,6%), increase higher manufacturer profit (65,9%), and increase the selling of advertised OTC drugs (62,2%).

Conclusions:

Although the advertisement on OTC isn't a reliable source of information about OTC drugs for the majority of respondents, it presents an impulse for more detailed searching information. According to our results, advertisements don't affect respondents' manners in dispensing OTC drugs, even though many respondents must stand higher patients' interest after publishing the OTC advertisement.

Author's CV: Eva Federičová is a student of 5th year of Faculty of Pharmacy MU. She has chosen the Department of Applied Pharmacy for her diploma thesis. The diploma thesis is focused on advertising for OTC medicines from the perspective of pharmacists and pharmacy assistants.

Supervisor: PharmDr. Bc. Dana Mazánková, Ph.D.

Veronika Mašková ¹, Dana Mazánková ¹

¹ Department of Applied Pharmacy, Faculty of Pharmacy, Masaryk University

Key words: Precision medicine, targeted therapy, neuroblastoma, effectiveness of treatment, toxicity of treatment

Background and aims:

Precision medicine, also known as personalized medicine, is a newly emerging field based on selecting suitable active substances and their combinations administered to a particular patient at the right time and in the correct order. This thesis aimed to evaluate the effectiveness and safety of personalized medicine procedures in pediatric patients with refractory or relapsed neuroblastoma.

Methods:

The tumor response to treatment was evaluated according to RECIST criteria (Response Evaluation Criteria in Solid Tumor), toxicity was assessed using Common Toxicity Criteria (CTC). The group analyzed consisted of 11 pediatric patients at the Clinic of Pediatric Oncology of the Faculty of Medicine in Brno. Treatment of the patients was carried out in three phases: first-line treatment, second-line treatment, and targeted treatment. The effectiveness of targeted therapy was evaluated according to RECIST criteria, including four types of examination: MIBG (metajodobenzylguanidinMRI of the whole body (magnetic resonance imaging), CT scans (computer tomography), bone marrow examination. MIBG, CT scans, and bone marrow examination were evaluated in four stages, MRI examination was evaluated in three stages. The same stages assessed MIBG and CT scans: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Bone marrow scans were assessed as bone marrow progression (BM-P), remission (BM- R), no response (BM-NR), and not evaluable (BM-NE). The most recent MRI of the whole body was assessed by complete response (CR), stable disease (SD), and progressive disease (PD).

Results:

Primary protocols were used in the first-line treatment, which includes the following protocols: RAPID COJEC, COG ANBL0532, COG ANBL02P1, COG ANBL1531, and the MATIN protocol. Patients in the second-line treatment received either the METRO 2012 protocol or COG ANBL1221, or a dendritic vaccine. In the next step, patients received targeted therapy; the medicinal products used included Sutent (Sunitinib malate), Inderal (Propranolol), Vinblastine (Vinblastine succinate), Xalkori (Crizotinib), Lorviqua (Lorlatinib), Kisqali (Ribociclib succinate), Zykadia (Ceritinib), Opdivo (Nivolumab), Ofev (Nintedanib esilate) and Stivarga (Regorafenib). All these medicinal products were used off-label, except Quarziba (dinutuximab beta), where the drug was used in accordance with the SPC. In the MIBG examination, 18% of the 11 patients were in the progressive phase, 9% in complete remission, and 37% in the stable phase, with the remaining 36% not known. In the MRI examination, 18% of the patients were in the progressive phase, 36% in the stable phase, and 46% not known. CT scans were recorded as complete remission in 9%, partial remission in 18%, stable disease in 27%, disease progression in 28% of patients and results unknown in the remaining 18%. Bone marrow scans showed remission of bone marrow in 18%, non-evaluable bone marrow in 18%, non-response in 9%, and results unknown in 55%. The final tumor response to the targeted therapy was generated from these obtained values, which were evaluated in four stages. Complete remission (i.e., the best tumor response to treatment) was in 9% of patients, 27% of patients were in the stable phase, and 64% were in the progressive phase.

Conclusions:

Tolerance to the targeted therapy was good. No patient experienced life-threatening toxicity, the maximum toxicity was hematological grade IV in one patient (9%), but it spontaneously resolved after discontinuation of the targeted therapy. The results suggest that neuroblastoma is a very aggressive tumor, which is very difficult to treat. However, these treatments, which are based on the knowledge of targeted therapy and precision medicine, open up new modern perspectives for treating high-risk tumors, which can exceptionally be treated with standard treatments.

Acknowledgement: The study was supported by the project SVV MUNI/A/1678/2020

Author's CV: Veronika Mašková, a fifth-year student at the Faculty of Pharmacy of Masaryk University.

Supervisor: PharmDr. Bc. Dana Mazánková, Ph.D.

Simona Bognarová ¹

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University

Key words: phantom pain, phantom limb, amputation, analgesics, non-pharmaceutical intervention, rehabilitation, virtual reality, mirror therapy

Introduction: Phantom pain is pain that can arises after amputation. The theoretical part explains the concepts of pain, amputation and phantom pain. What are its symptoms, causes and how the pain can be solved. A number of analgesics, anesthetics, antidepressants, anticonvulsants, muscle relaxants, benzodiazepines and adrenergic receptor blockers for phantom pain has been found in the literature. Non-pharmaceutical intervention has been used to treatment, such as targeted muscle reinnervation, rehabilitation, transcutaneous electrical nerve stimulation, mirror therapy and virtual reality therapy.

Aim: The aim of the clinical part was to find out the most commonly used drugs and non-pharmaceutical interventions on phantom pain in hospital T.G.M. Hodonín. The presence of side effects and the quality of the respondent was very important.

Methods: The research for the theoretical part was perform using Web of Science database. The research for clinical part was perform using a questionnaire with twenty questions. The questionnaire is composed of demographic data, number and places of amputations for the clinical part. The main part of questionnaire concerned the course, intensity of pain and methods of pain relief. An interview was conduct with the respondents, using a questionnaire. Then I got necessary information for processing the data into pie charts.

Results: There were accept 31 questionnaires for evaluation in total. In cooperation with MUDr. Martina Vojtková and MUDr. Paula Cvachová. More than half of the respondents suffered phantom pain after amputation. These pains occurred in half of the respondents during one week after amputation. 85 % of respondents used the analgesics on phantom pain (Dipidolor, Novalgin, Tramal, Ultracod, Ibuprofen, Paracetamol, Almiral, Dolsin, Palgotal and Zaldiar). 44 % of respondents used non-pharmaceutical intervention. Rehabilitation, massage, ozone therapy and acupuncture were very often. Only 29 % of respondents had reduced quality of life because of phantom pain.

Conclusion: The results showed combination of analgesics the benefits, but only for a short time. Typical side effects were appetite disorders and fatigue. Unfortunately, non-pharmaceutical interventions were not use often. Non-pharmaceutical interventions include mirror therapy and virtual reality therapy. A small number of respondents participated in these methods. I hope will be to conduct bigger randomized studies with a larger number of respondents in the future.

Author's CV: Simona Bognarová is currently studying the fifth year of the Pharmacy master‘s degree programme at the Faculty of Pharmacy of Masaryk University.

Supervisor: PharmDr. Lenka Paráková, Ph.D.

Marie Mieresová ¹

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University

Key words: radiofrequency ablation of atrial fibrillation, postablation recurrence, prognostic factor, prognostic model, RAAS

Introduction: Radiofrequency ablation (RFA) has become a routine treatment approach for atrial fibrillation (AF). The aim of this study was to identify independent predictors of late AF recurrence after RFA, develop a new prognostic model and compare its predictive value with the predicitve value of chosen preexisting prognostic models. The next aim was to investigate the effect of preablation renin-angiotensin-aldosterone system (RAAS) inhibitors use on postablation AF recurrence risk in an individual patient.

Methods and results: From 296 consecutive patients who underwent RFA of AF during 2019 in St Anne's University Hospital in Brno, 221 were included and their data retrospectively analyzed. During a median follow-up of 13 months, late AF recurrence was detected in 45,2 % patients (N = 100). Univariate analysis showed non-paroxysmal AF, BMI > 30 kg/m², left ventricular ejection fraction < 50 %, left atrial (LA) enlargement > 43 mm, bundle branch block / QRS duration > 120 ms and AF recurrence during blanking period to be significantly associated with recurrent AF. These variables were included in multivariate analysis which identified only non-paroxysmal AF (HR 1,95, 95 % CI 1,26–3,92, p = 0,003), LA enlargement > 43 mm (HR 1,66, 95% CI 1,03–2,70, p = 0,039) and AF recurrence during blanking period (HR 2,48, 95 % CI 1,61–3,14, p < 0,001) as independent predictors of late AF recurrence after RFA. Based on these findings, RF 0–3 PL score composed of two predictors [non-paroxysmal AF (2 points) and LA enlargement > 43 mm (1 point)] was developed. ROC analysis showed RF 0–3 PL model (AUC 0,732, 95 % CI 0,665–0,799) had a predictive value comparable with APPLE, DR FLASH and 0-1-2 PL models and significantly higher than HATCH and CHA₂DS₂-VASc models. The preablation angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers use wasn´t associated with lower late AF recurrence risk after RFA (HR 1,26, 95 % CI 0,84–1,90, p = 0,265).

Conclusion: Non-paroxysmal AF, LA enlargement > 43 mm and early AF recurrence were identified as independent predictors of late AF recurrence following RFA. Developed prognostic model RF 0–3 PL may facilitate the risk assessment of late recurrent AF following RFA in an individual patient. Despite the undoubted benefits of RAAS inhibitors for AF patients, our findings do not support their routine administration before RFA.

Author's CV: Marie Mieresová is a fifth-year student of the Master's degree program at the Faculty of Pharmacy of Masaryk University.

Supervisors: MUDr. Tomáš Parák, Ph.D., MUDr. Karel Lábr, Ph.D.

Veronika Krupicová ¹

¹ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University

Key words: Alzheimer’s disease, dementia, cognitive enhancers

Increasing age is one of the uncontrollable risk factors for developing dementia. It increases the prevalence of cognitive impairment, which can later develop into dementia. Another reported risk factor for developing dementia is female gender.

The progression of dementia can be slowed and the onset of severe phases can be delayed by early detection, diagnosis and appropriate treatment. Treatment is primarily based on the knowledge of the individual neuropsychiatric syndromes of Alzheimer's disease, which cannot currently be cured with drugs, which is why symptomatic or disease-modifying approaches are chosen. Prevention is also emphasized, as preventive measures such as following a healthy lifestyle play an important role in delaying the onset of severe phases of dementia. It is therefore appropriate to raise awareness of the disease among the general public and to encourage an active and healthy lifestyle.

In this thesis I evaluate the pharmacotherapeutic approach to treating patients with dementia that is being used by a type of social care facility and the effect of risk factors on patients' cognitive function. The risk factors assessed are gender, age, patient medication, and social care facility in which a patient is placed. The cognitive function of patients was monitored using three simple tests - POBAV, ALBA and TKH. These tests are quick, easy, and funny for patients, yet they can accurately determine a patient‘s cognitive function.

It was confirmed that increasing age contributed to the deterioration of cognitive function in the observed group of fifty patients with dementia. Female gender also outnumbered the group of patients up to three-fold. The facilities had significantly different pharmacotherapeutic approaches. The AD centre in Třebíč used cognitive enhancing drugs frequently and the Retirement home in Plaveč used them rarely. The facilities also chose different psychopharmaceuticals for patient therapy. After the drugs used in these two facilities were evaluated according to the Beers criteria from 2012 and their updated version from 2019, I observed that potentially inappropriate medication was only minimally used in older adults.

Supervisor: PharmDr. Bc. Hana Kotolová, Ph.D.