Original Research article

Anticoagulants are used to treat different thrombotic conditions, and patients should be educated on administration, safety, and adverse reactions associated with their medication to achieve the optimum therapeutic effect. Pharmacists are an essential part of providing pharmaceutical care and a reliable source of information for patients; therefore, their knowledge of medications must be up-to-date. This study aimed to assess Urmia’s community pharmacists’ knowledge about the utilization, safety, and interactions of commonly prescribed anticoagulants.

This questionnaire-based cross-sectional study was conducted from September 1st, 2020, to February 31st, 2021, in Urmia, Iran. A 35-item questionnaire was designed based on previous studies and researchers’ experience. The questionnaire was validated, and its final version was presented to randomly selected community pharmacists in Urmia. Filled-out forms were collected and analyzed in the context of three main areas of safety, adverse reactions, and administration.

Ninety-five participants filled out the questionnaire, for whom a mean score of 16.53±4.56 was calculated. Out of 95 pharmacists, only 30 scored ≥50% correct answers. No significant correlation was observed between age, years of employment, and pharmacists' competency in correctly answering the questions (p-value>0.05). The participants' overall knowledge was more reliable for warfarin than for enoxaparin and DOACs, with a p-value<0.001.

The results of this study suggest a lack of sufficient knowledge among Urmia’s community pharmacists concerning commonly prescribed anticoagulants. This puts patients at risk for therapy complications and should be addressed accordingly.

Toward a Recognition of Key Role players in Community Pharmacy

Monireh Afzali, Ali Rajabzadeh, Soroush Ahmadi, Fatemeh Soleymani, Abbas Kebriaeezadeh, Shekoufeh Nikfar

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e2: 1-8

Although private community pharmacies are identified as health care facilities, they are highly affected by business management issues. As an example of public-private partnership in the health sector, private community pharmacies have multiple key stakeholders. This study is a comprehensive stakeholder analysis which aims to identify, classify, and analyze multiple key stakeholders involved in the community pharmacy business and their interests, relationship, and behavior. This understanding of the context and evaluation of the above factors will help community pharmacy managers develop suitable strategies to properly manage the stakeholders in order to better achieve organizational goals. A focus group was conducted with key informants. The first phase of the focus group identified stakeholders through brainstorming techniques. In the second phase, stakeholder analysis and classification were performed using a three-dimensional matrix. Identified stakeholders were differentiated by levels of relationship with community pharmacies. They were analyzed regarding three attributes of power, legitimacy, and urgency, and were grouped into eight classes including definitive, dormant, dominant, discretionary, dependent, demanding, and dangerous stakeholders and non-stakeholders. The results of the focus group were converted to a structured questionnaire and confirmed in several face-to-face interviews until reaching a consensus. Four main levels of relationship and eight categories of stakeholders were identified by qualitative analysis through conducting a focus group with key informants. The core stakeholders include pharmacy licensee, licensee-owner, responsible pharmacist, customer, prescriber, health insurance, regulatory body, and staff. The core stakeholders possess three saliences of power, legitimacy, and urgency. Therefore, they are directly involved in decision making. Further deliberations are necessary to analyze the behavior of stakeholders and investigate the communication model.

Antibacterial Effect of Aqueous and Ethanol Extracts of Moringa oleifera Leaves on Methicillin Resistant Staphylococcus aureus (MRSA) Isolates obtained from sampled in a University Community.

Methicillin Resistant Staphylococcus aureus (MRSA) are strains of the Staphylococcus aureus that are resistant to the action of methicillin and related beta-lactam antibiotics. MRSA infections have now become a major public health concern and its prevalence is also increasing globally. This study focused on the prevalence of MRSA obtained from clinical samples. The failed antibacterial agent conventional used for treatment necessitated the investigation of Antibacterial Effect of Aqueous and Ethanol Extracts of Moringa oleifera Leaves on Methicillin Resistant Staphylococcus aureus (MRSA) Isolates. A total of 296 samples were collected from Armpit, Ear, High Vaginal, Mouth, Nose swabs, Urine and Semen, from which 143 (48.3%) isolates of S. aureus were obtained. The MRSA prevalence 105(35.5%). There were no association (no significant difference P>0.05) in the prevalence of S. aureus and MRSA with regards to Age distribution, Sex and Sample types. A Total of 35 selected isolates of MRSA were analyzed for their antibiotic susceptibility and effect of Aqueous and Ethanol Extracts of Moringa oleifera Leaves. They were highly susceptibility to Ciprofloxacin 26(74.3%), Gentamicin 31(88.6%), Streptomycin 32(91.4%) and Levofloxacin 32(91.4%). However, low levels of MRSA susceptibility were recorded for Vancomycin 21(60%) and Ampiclox 31(88.6%). Multidrug resistant (isolates resistant to drug agents ≥ 4) recorded is 9(25.7%) of the 35 isolates studied. Comparing the anti-MRSA property of Moringa oleifera leave extracts between aqueous at ≤ 12.5 mg/mL and 70% ethanol extracts at 25 mg/mL on 35 selected MRSA isolates using Mann Whitney test their Mean ± SD zones of minimal inhibition are (1.86 ± 5.91 mm) and (0.54 ± 2.16 mm) respectively. Statistically at P˂0.0.5 the null hypothesis was rejected P= 0.047. Meaning aqueous extract mean zones of inhibition is higher than that of 70% ethanol extracts. Therefore, aqueous extraction of M. oleifera leaves should be studied intensively as a potential source for drug development for the treatment of MRSA infections.

Diuretic Activity of the Flavonoid Pinostrobin Previously Identified from the Species Renealmia alpinia

Carolina Lopera-Londoño, Cristhian Melan, Julieta Vásquez, Alejandro Serna, Arley C. Patiño, Dora M. Benjumea

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e4: 1-6

Renealmia alpinia is a plant traditionally employed as antiophidic, pain reliever, antipyretic, and antiemetic. Its main metabolites are flavonoids, with pinostrobin as the most abundant compound of this plant species. In this study, we determined the diuretic activity of pinostrobin, previously identified from the species Renealmia alpinia in normal mice.

The evaluation of the diuretic activity of the flavonoid pinostrobin was carried out at doses of 5, 10, and 20 mg/kg of body weight. The diuretic activity was evaluated using the Kau et al. (1984) method with modifications made by Benjumea et al. (2005), using mice instead of rats. Metabolic cages equipped with graduated cylinders were used to measure the volume of urine excretion at 2, 4, and 6 hours. At 6 hours, pH and conductivity were measured, and the concentration of excreted sodium, potassium, magnesium, and calcium ions was estimated by ion chromatography. Creatinine, albumin, blood urea nitrogen, and urea of mice blood were analyzed.

There was an increase of 32% and 38% at a dose of 10 and 20 mg/kg, respectively, in the urinary excretion of water by pinostrobin, an elimination of sodium concentration similar to furosemide at 5 and 10 mg/kg, An increase in potassium concentration of 52% at 10 mg/kg and a higher magnesium excretion of 85% at 5 mg/kg, were statistically significant compared to furosemide.

Pinostrobin showed a diuretic effect increasing the volume of urinary excretion in mice and excretion of sodium, potassium, magnesium, and calcium ions, with a possible mechanism in the loop of Henle.

Many drugs and regular exercise may have effect on male fertility. Therefore in the present study we investigated the effect of Atorvastatin and Endurance training on serum levels of testosterone,Leydig ,spermatogonia, Spermatocyte cells numbers and testicular morphology and  morphometric evaluation in rats. 30Wistar rats(230±10g)were randomly divided into 6 groups:control, endurance training,atorvastatin(5 mg/kg and 10 mg/kg),the endurance training + atorvastatin (5 mg/kg and 10 mg/kg),5 rats per group. Drug intervention groups received atorvastatin for 4 weeks using gavage.Training groups also run a rodent treadmill 5 days a week for 4 weeks(speed of 10 m/min for 10 min in first week and other week: 16 m/min for 50 min) Serum testosterone level was measured by ELISA Kit.The results showed in the endurance training+atorvastatin 10 mg/kg, morphological disruption of testicular was observed.The number of Leydig, spermatogonia and Spermatocyte as well as blood testosterone level and germinal epithelium thickness were significantly decreased in the endurance training+atorvastatin 10 mg/kg compared to the control group(p< 0.05). In conclusion,the results of this study showed the negative effect of the combination of endurance training and  high dose atorvastatin (10 mg/kg ) on testicular tissue and male reproductive system due to decreased levels of testosterone in rats.

Optimizing Outpatient Medication Management: The Impact of Clinical Pharmacists on Identifying and Addressing Drug-Related Problems

Soheil Roshanzamiri, Niloufar Taherpour, Kaveh Eslami, Reza Ganji, Kourosh Sadeghi, Farhad Najmeddin, Elham Hadidi, Mandana Izadpanah, Masoud Mahdavinia

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e7:1-7

Medication Therapy Management Services (MTMS) are effective strategies to reduce Drug-Related Problems (DRPs) and associated healthcare costs. Given the high prevalence of DRPs in outpatient settings and the lack of an effective process to detect such problems in Iran, we decided to evaluate the type and number of DRPs identified by clinical pharmacists in a university-affiliated Pharmacotherapy Clinic in Khuzestan province, South of Iran. In this cross-sectional study, 150 eligible outpatients were included. At a university-affiliated pharmacotherapy clinic, pharmacy students took patients' histories and referred them to clinical pharmacists for DRP evaluation and detection. Appropriate interventions were then implemented in collaboration with patients and their healthcare providers to resolve the problems. Approximately 3.56 DRPs per patient were identified during a nine-month study period. The most prevalent DRPs were lack of education or information (32.40% [174/537]), undertreated indications (17.31% [93/537]), and patient compliance (15.27% [82/537]). Clinical pharmacists detected 537 DRPs, implemented 525 interventions, and performed 0.977 interventions per DRP. The provision of information (57.52% [302/525]) and change of therapy (21.71% [114/525]) were the most frequent types of clinical pharmacist interventions. This study revealed deficiencies and limitations in our healthcare services, resulting in a significant prevalence of DRPs. Implementing pharmaceutical care practice models, such as Pharmacotherapy Clinics, where clinical pharmacists integrate their experience and knowledge in a patient-centered manner, is the most effective method for preventing and managing these issues

Evaluation of Antioxidant, Anti-Tyrosinase, and Anti-Melanoma Activities of Phlomis Rigida

Erfan Abdoli, Parisa Sarkhail, Mahban Rahimifard, Mona Salimi

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e8: 1-6

The aim of this study is to evaluate in vitro cytotoxicity of Phlomis rigida (P. rigida) aerial parts on the malignant melanoma cells as well as assess its antioxidant and anti-tyrosinase activities. The total phenolic and flavonoid contents along with in vitro antioxidant and anti-tyrosinase activities of P. rigida MeOH (80%) extract were determined using Folin-Ciocalteu, aluminum chloride, DPPH radical scavenging, and mushroom tyrosinase assays, respectively. The cytotoxicity of the extract was investigated by determination of the cell viability using MTT assay on the normal fibroblast (NIH3T3) and malignant melanoma (SKMEL-3) cells. The extract showed a weak scavenging activity with SC50 value higher than 5 mg/mL and the tyrosinase inhibitory activity with an IC50 value of 1.092 mg/mL. Interestingly, the extract was not toxic on NIH3T3 cells at all tested concentrations (0.0001-0.1 mg/mL), however, it could significantly reduce cell viability on SKMEL-3 cells, particularly at higher concentrations than 0.01 mg/mL (the IC50 ≈ 0.148 mg/mL). Based on our results, a selective cytotoxic effect against SKMEL-3 cells was found for the extract of P. rigida compared with NIH3T3 cells. Therefore, it is recommended as a good candidate for further investigation to discover bioactive natural agents in melanoma treatment

The Effect of Ash Water on Viruses

Ishak Afşin Kariper, Saliha Esra Bolsu Kariper

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e9: 1-7

This study conducted tests on various viruses with ash water, which can be obtained very simply. The study aims to produce a liquid that can block viruses and be obtained from waste combustion products, unlike disinfectants that have a place in daily life. The present study tested ash water containing methyl stearate and methyl esters, octadecenoic, octadecanoic acid, and methyl esters and their derivatives against DNA- and RNA-based viruses. Bovine Rotavirus, Bovine Coronavirus, and Parainfluenza virus-3 were used as RNA-based viruses, and Bovine Adenovirus and Bovine Herpesvirus were used as DNA-based viruses. MTT tests were conducted in the in-vitro cytotoxicity analysis of healthy cells. After the MTT tests, ash water was filtered and adjusted to pH 7.4. It was found that, when diluted at the rate of 1/32, ash water showed no harmful effect on healthy cells. In the tests against Bovine Parainfluenza virus, the compound showed no activity. In the first 24 hours, the compound was found to block the Bovine Coronavirus, one of the RNA-based viruses, by 100% at 0.01 MOI (10-6) concentration and by 50% at 0.1 MOI (10-5) concentration. In the first 24 hours, the compound was found to block Bovine Rotavirus by 100% at 0.1 and 0.01 MOI (10-4 and 10-5) concentrations and by 50% at 1 MOI (10-3) concentrations. The compound showed no activity in the test conducted against Bovine Herpesvirus, one of the DNA-based viruses. When tested against Bovine Adenovirus, the compound blocked the virus by 50% in the first 24 hours at 0.01 MOI (10-3) concentration. As a result, it has been observed that ash water, which can be easily produced instead of disinfectants containing chemicals, is effective against two viruses. It has been understood that if the studies on ash water are improved, a natural liquid effective on viruses can be developed.

Herbal medicine, as defined by WHO, is finished labeled medicinal products that contain active ingredients of plants, whether in the crude state or as plant preparation. Ocimum gratissimum has been traditionally used to alleviate symptoms of illness such as stomach disorders, fever, and cough. This study aimed to evaluate the phytochemical, physiochemical, and comparative antibacterial activity of the methanol and n-hexane extracts of Ocimum gratissimum stems against Methicillin-Resistant Staphylococcus aureus (MRSA) and Proteus vulgaris. Phytochemical screening was conducted using standard methods. Physicochemical analysis was carried out, including moisture content, extractive values, and ash values. Biochemical tests such as catalase, coagulase, indole, and fermentation were carried out to identify the organisms. The minimum inhibitory concentration (MIC) and the susceptibility of the organisms to the various concentrations of the two extracts were determined using the agar well diffusion technique. Phytochemical screening results revealed the presence of phytoconstituents such as alkaloids, saponin, tannins, cardiac glycosides, and terpenoids. The physicochemical evaluation results confirm the quality of the crude drugs as the results obtained fall within standard ranges for the different parameters used for crude drug standardization. Susceptibility test results revealed the zones of inhibition of methanol extracts of Ocimum gratissimum stem against MRSA according to the various concentrations as (19.20, 17.33, 14.66, 14.33, 13.6, and 12.33) with MIC at 25 mg/ml while against P. vulgaris as (16.6, 16.6, 14.30, 13.6, 13 and 12.6) with MIC at 12.5 mg/ml. This study has clearly shown that the methanol extract of the stem of Ocimum gratissimum has a moderate degree of inhibition on both MRSA and P. vulgaris. However, this crude drug is seen to be slightly more effective against MRSA in comparison to its antibacterial activity against P. vulgaris. Further investigations should be conducted to develop newer and more effective drugs for in vivo and in vitro use.

Review article

Investigating effective methods of immune induction as pre-exposure measures for rabies in immunocompromised patients: a mini-review

Saman Pazira, Sepideh Bourenjan Shirazi, Dr Behzad Pourhossain, Rouzbeh Bashar, Ehsan Zafari, Maryam Fazeli

International Pharmacy Acta, Vol. 6 No. 1 (2023), 1 Dey 2023, Page e6: 1-11

Background: Neurotropic rabies virus is the cause of fatal encephalitis. Due to the definite mortality of this disease, after symptoms appear, it is of great importance to implement appropriate prevention methods before and after exposure in rabid-bitten people. Knowing that the immune system plays a key role in preventing symptoms after taking efficient measures to control and prevent rabies, this issue becomes imperative in immunocompromised patients. This study has tried to compare all the effective methods of prevention before and after exposure in people with a weak immune system by reviewing various reliable articles and sources.

Methods: In this study, all articles were found online until March 2022 in English through several search engines, including PubMed, EMBASE, and Google Scholar by searching the keywords immunodeficiency, HIV/AIDS, organ transplantation, bone marrow transplantation, and tumors. Malignancy and chemotherapy, hemodialysis, use of systemic corticosteroids, pregnancy alone, and also together with prevention methods before and after exposure to rabies were searched. All the articles related to the measures of controlling and preventing rabies in all healthy individuals and patients with underlying diseases, immunocompromised patients, and pregnant women were considered and analyzed. Methodological integrity was ensured by utilizing the Cochrane risk and bias assessment tool.

Results: Due to duplicate records, non-citability, and other reasons, 16 out of 60 extracted articles were excluded before the screening. Approximately 44 articles were screened, and all remaining reports were eligible for review. The most frequent methods found in the articles regarding prevention before and after exposure to rabies in individuals suffering from each of the mentioned diseases were investigated.

Conclusion: Paying attention to immunodeficient patients is highly imperative in the mechanisms of the health system. It can be said that since the rabies vaccine is an inactive one, it is safe to use in most immunocompromised cases

Overuse of antibiotics in recent decades has led to the emergence of antibiotic-resistant infections. Drug resistance is now regarded as a major threat to global public health. For this reason, the phenomenon of antibiotic-resistance caused that health care professionals looking for new types of effective antimicrobial agents against the threat of traditional antibiotic-resistant pathogens. In their role as effector molecules in the innate immune response, antimicrobial peptides (AMPs) carry out numerous important tasks. Through interactions with negatively charged phospholipids, cationic AMPs have the ability to damage microbial cell membranes. Positively charged cationic AMPs reduce the risk of resistance, which is a major advantage compared to available antibiotics. In recent decades, a large number of non-disulfide-Bridges peptides (NDBPs) with medicinal properties have been isolated from the venom of the scorpion. Therefore, scorpion venom is a tremendous source of raw AMPs for design and development of novel drugs against antibiotic-resistant pathogens. NDBPs are effective against different types of antibiotic-resistance bacterial strains, including methicillin-resistant staphylococcus aureus (MRSA). In this review, a diversity of NDBPs that are effective against the resistant pathogens was discussed.