Iranian Journal of Pharmaceutical Research
Year:2018 | Volume:17 | Issue:SUPPLEMENT|Papers Count:20

Different branches of science are expanding very fast and there are vast volumes of new information which are progressively discovered and added to the present human knowledge. With no doubt, pharmaceutical sciences is amongst the most dynamic disciplines of science that its content isattributed to different basic and applied researches including studies in the field of physical and organic chemistry, engineering, biochemistry, biology, pharmacology and pharmacotherapy. These researches are aimed to understand how to develop new drugs, optimize their delivery to the body and translate these integrated understanding into new therapies against human disease as well as improved community health.

Treatment of acute pain and hemodynamic changes after surgery is extremely important. Various drugs for pain relief after surgery have been studied. The aim of this study was to evaluate the effect of a single dose of oral pregabalin on hemodynamic changes and duration of analgesia after spinal anesthesia in orthopedic surgeries of tibia fractures. This clinical trial was carried out on 120 patients with fractures of the tibia bone in 2014 in city of Zahedan. Sampling was conducted using randomized blocks and patients were placed into pregabalin (150 mg PO 1 h before anesthesia) and placebo groups. Duration of analgesia, severity of anxiety, mean arterial pressure, and pulse rate were evaluated in both groups. The mean age of the patients was 34.8 ± 21.7 years and 84 patients (70%) were male and 36 (30%) were female. There were nosignificant differences at baseline characteristics of the patients in two arms of the study. After surgery, mean arterial pressure, pulse rate and anxiety, were significantly lower in intervention group. Also the duration of analgesia was significantly longer in intervention arm (185.3 ± 4.9 vs 36.9 ± 13.9, P<0.01). Dizziness as a side effect of pregabalin was observed in 21 and 11 subjects in intervention and placebo groups, respectively (P<0.01). The present study showed that a single dose of oral pregabalin increases the duration of analgesia and maintains hemodynamic stability in orthopedic surgery patients.

Hyperalgesia is a common clinical phenomenon among opioid dependent patients on methadone maintenance therapy (MMT) and it may be associated with undertreated pain and/ or therapeutic failure. This study aimed to investigate association between serum methadone concentration (SMC) and cold pressor pain responses. Cold pressor pain responses in 147 opioid dependent patients on MMT were assessed using cold pressor test (CPT) at 0 h and at 2, 4, 8, 12, and 24 h after the dose intake. Blood samples were collected at 24 h after the dose. Serum methadone concentrations were measured using the Methadone ELISA kit andclassified into two categories: <400 ng/mL and ³ 400 ng/mL. Eighty-eight patients (59.9%) had trough concentrations of <400 ng/mL and 40.1% had trough concentrations of ³ 400 ng/mL. There were significant effects of SMC on the cold pressor pain threshold (p=0.019). Patients with concentrations <400 ng/mL had significantly higher (almost 60% higher) cold pressor pain threshold (adjusted mean (95% CI) =30.15 (24.29, 36.01) s) compared to those with concentrations of ³ 400 ng/mL (18.93 (11.77, 26.08) seconds). There was also a 20% difference in pain tolerance, and 6% difference in cold pressor pain intensity score, neither of which were significant statistically (p>0.05). Our results suggest an association of trough methadone concentration with the cold pressor pain threshold among opioid dependent patients on MMT. It would be useful to study the mechanisms underlying this association to help managing pain in such a population.

Cancer constitutes a huge burden on societies in countries with any level of economic development. Prostate cancer is the first most diagnosed cancer of men in developed countries and the forth one in developing countries in terms of incidence rate. It is also the third incident cancer of men in Iran along with a prevalence of about 10, 000 cases. Castration-resistant prostate cancer (CRPC) is a severe stage of the disease with a number of newly discovered treatment options. These therapeutic alternatives including abiraterone acetate, enzalutamide, cabazitaxel, immunotherapy with sipuleucel-T, radiopharmaceuticals and bone-targeted therapies (zoledronic acid, denosumab) along with docetaxel have made the decision making process complex and challenging for clinicians. In addition to the challenges of selecting the best-fit treatment, high costs of new pharmaceuticals and technologies necessitates the health policy-makers to develop practice guidelines in adaptation with local resources and limitations. The aim of this paper is to review the clinical guidelines for the management of CRPC. For better comprehension of guideline recommendations, the main clinical trials on new treatments were also identified. The efficacy and safety outcomes including but not limited to overall survival, progression free survival, quality of life and adverse effects were summarized. The guidelines of American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EUA), Spanish Oncology Genitourinary Group (SOGG), Asian Oncology Summit, Saudi Oncology Society-Saudi Urology Association combined guideline, National Institute for Health and Care Excellence (NICE) and Canadian Urological Association-Canadian Urologic Oncology Group (CUA-CUOG) were covered in this paper.

Methotrexate as a single agent chemotherapy in most women with low risk gestational trophoblastic neoplasia (GTN) has been associated with high treatment rate. Combination of methotrexate with Vitamin A due to reduced number of chemotherapy regime courses is one of the treatment options for patients with low-risk GTN. Therefore, this study was performed with aim to determine the efficacy of combination therapy of Methotrexate with Vitamin A in low risk GTN treatment. This randomized clinical trial was performed on 49 patients with low risk gestational trophoblastic neoplasia. The treatment group (Group A=19 cases) weekly received Methotrexate 50 mg/m2, and Vitamin A 200000 IU, intra-muscular, and the control group (Group B=30 cases) only received Methotrexate 50 mg/m2 weekly. All patients were followed up for 8 weeks. Then, treatment outcomes were compared between two groups, and response to therapy was assessed in two groups by evaluation of HCG serum level. P<0.05 was considered significant. Mean of B-HCG serum level after 4 weeks in Group A and Group B was 68.5 mIu/mL and 360 mIu/mL, respectively (P=0.018), and after 8 weeks was 1 mIu/mL and 12 mIu/mL, respectively (P=0.074). Combination therapy of Methotrexate and Vitamin A in low risk GTN is associated with shorter duration of chemotherapy.

Cytotoxicity and mitochondrial parameters were studied in isolated lymphocytes and their mitochondria obtained from occupationally exposed nurses through inhalation exposure to antineoplastic drugs and results were compared to those of unexposed nurses. The group of occupationally exposed nurses consisted of 50 individuals ranging in age from 30 to 35 years. The control group included 50 nurses who were not occupationally exposed to the preparation and handling of antineoplastic drugs and their anthropometric and biochemical characteristics were similar to those of the expose group. All cytotoxicity and mitochondrial parameters evaluated in exposed group were significantly increased (P<0.05) compared to the unexposed control group. Finally, the results of our study suggest that using antioxidant, mitochondrial and lysosomal protective agents can be promising drug candidates for the hospital staff in the risk of exposure to exposure to antineoplastic drugs.

Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Despite the progress in the treatment of AMI, streptokinase is still being used in many countries. Because of the critical condition of patients with AMI and complications of streptokinase therapy, this study was performed to evaluate the pattern of adverse drug reaction (ADRs) induced by streptokinase and its associated risk factors in patients with acute ST elevation MI.A prospective cross-sectional study in a 14-month period was done at the university affiliated referral cardiovascular center. The Naranjo probability scale and Food and drug administration (FDA) criteria for severity of ADRs were performed for assessing the ADRs. The linear and logistic regression tests were used to evaluate the correlation between ADRs and study risk factors.During the study period, 217 patients who received streptokinase were entered. The majority of patients (n=191) experienced at least one ADR. Six patients died in-hospital mainly because of cardiac causes. The history of drug allergy was the main predictor in occurring of ADRs (Odds ratio: 3.26; 95% CI: 1.48-457.6; p=0.026). The most serious ADR was hemorrhagic stroke with a 1.4% incidence. Hypotension was one of the most occurred ADR (n=75). Anaphylactic shock was not detected in this study.In summary, our study showed that the history of drug allergy is the main predictor in occurring of ADRs by streptokinase. Furthermore, streptokinase therapy was associated with a higher rate of hemorrhagic stroke in Iranian population.

Availability and affordability of medicines are crucial to achieving success in prevention programs, particularly in developing countries. The aim of this study was to determine the availability and affordability of cardiovascular medicines for secondary prevention in Tehran province of Iran. A cross-sectional survey was conducted in Tehran province in 2015, using the 2nd edition of the World Health Organization/Health Action International methodology. Data on the availability and affordability of 21 selected cardiovascular medicines were collected from the public and private healthcare sectors. A total of 120 facilities were included in the survey and the medicines in this survey were both original and lowest-price generic. Lowest-price generic equivalent medicines were highly available (>80%) in almost all pharmacies of both public and private sectors, while the availability of original brand medicines was highly poor in public and private pharmacies. The median price ratios were 0.72 to 0.76 for generic medicines. The treatment of cardiovascular diseases with lowest-price generic equivalent medicines was generally affordable; moreover, less than a single day’s wage was adequate to purchase a monthꞌs supply of the lowest priced generic of the surveyed medicines. The availability of the selected generic medicines for the secondary prevention of cardiovascular diseases is high in both public and private sectors and they were affordable for low-paid unskilled government workers in the province. The result of this study demonstrates that the supply policies pertaining to generic medicines have been implemented successfully.

According to studies, a significant association exists between the low levels of vitamin D and cardiovascular diseases such as myocardial infarction (MI). In a prospective case control study, 88 patients with acute coronary syndrome (ACS) including ST elevation myocardial infarction (STEMI) and Non-STEMI were enrolled. The plasma level of 25-hydroxy vitamin D [25 (OH) D] was obtained at the time of acute MI. To assess the association between study variables logistic regression analysis was done. The overall rate of vitamin D deficiency was documented in 59.1% with the significantly higher prevalence rate in STEMI group (77.5% versus 43.7%; p=0.001). In STEMI group, the plasma level of 25 (OH) vitamin D was significantly lower than non-STEMI group (13.5 7.7 ± versus 24.3 14.9 ±; p=0.001). Vitamin D deficiency was the main predictor in occurring the ST elevation type of MI (Odd ratio: 8.1, 95% CI: 2.3 – 28.2; p=0.001). The results of the present study demonstrated a higher prevalence of vitamin D deficiency among ACS patients. Furthermore, vitamin D deficiency was responsible for occurring ST elevation type of MI among ACS patients. Large studies are needed to confirm these findings.

The current study was conducted to determine prevalence and antimicrobial susceptibility patterns, ESBL, AmpC and carbapenemase- producers among clinical isolates of Enterobacteriaceae. Three hundred and seven non-duplicative clinical isolates were collected from hospitalized patients in five medical centers in Azerbaijan, Iran. Initial screening for β-lactamase production was performed using disc agar diffusion according to Clinical Laboratory Standards Institute (CLSI) guidelines. Phenotypic confirmatory tests was done using total ESBL/AmpC confirm kit, KPC/MBL and OXA-48 confirm kit according to manufacturer’s instructions. The overall prevalence of ESBL, AmpC, and carbapenemase-producing strains were 42.7% (131.307), 14.0% (43.307) and 4.9% (15.307), respectively. The prevalence of ESBLs was 38.35%, 64.9% and 35.7% for E. coli, K. pneumoniae and E. cloacae, respectively. Carbapenemase activity was only observed among 15 K. pneumoniae isolates and detected phenotypes include MBL (9.57, 15.8%), KPC (4.57, 7.0%), and OXA-48 (2.57, 3.5%). Fourteen out of 307 isolates (4.6%) were recognized to have ESBL or AmpC hyper-producer with decreased cell wall permeability phenotype. All 4 shigella strains were positive for ESBL and 4 isolates of P. mirabilis, 2 isolates of M. morganii and 1 seratia spp. were detected as AmpC producer. The only C. freundii strain isolated was positive for both ESBL and AmpC. This study reveals high prevalence of multidrug-resistant (MDR) b-lactamase-producing Enterobactericeae reaching 89.5%. Imipenem and meropenem showed potent antibacterial activities against all MDR b-lactamase-producers except for carbapenemase producers. After carbapenems, amikacin, piperacillin/tazobactam and amoxicillin/clavulanic acid were second the most effective drugs against b-lactamase-producing E. coli isolates.

Hypoactive sexual desire disorder (HSDD) is the most prevalent female sexual dysfunction(FSD) and its bio-psychosocial multifactorial etiology justifies its multifaceted treatment. In Persian Medicine (PM), the weakness of the main organs (heart, brain and liver) is one of the important causes of lack of sexual desire; hence, their strengthening is a priority during treatment. Melissa officinalis is one of the medicinal plants with tonic characteristics for the main organs in PM and was used for treatment in this study. The aim of the present study was to evaluate the efficacy and safety of M. officinalis in the improvement of HSDD in women. Eighty nine (89) eligible women suffering from decreased sexual desire were randomly assigned to groups. The participants received medication (500 mg of aqueous extract of M. officinalis) or placebo 2 times a day for 4 weeks. Changes in scores of desire, arousal, lubrication, orgasm, satisfaction and pain were evaluated at the end of 4 weeks of treatment using the Female Sexual Function Index (FSFI) questionnaire in the two groups. Forty three participants completed the study. The increase in desire (P<0.001), arousal (P<0.001), lubrication (P<0.005), orgasm (P<0.001), satisfaction (P<0.001), pain (P<0.002) and FSFI total score (P<0.001) in the M. officinalis group was significantly more than that of the placebo group. The willingness to continue treatment was significantly higher in the M. officinalis as compared to the placebo group (P<0.001). M. officinalis may be a safe and effective herbal medicine for the improvement of HSDD in women.

Nipple fissure is a common problem during breastfeeding. Zizyphus Jujube Fruits is one of the oldest medicinal plants which can heal wounds through its antimicrobial and anti-inflammatory properties. This study aimed to determine the effect of jujube lotion on the recovery of breast fissure. This double-blind clinical trial recruited 100 primiparous lactating women who were randomly divided into two groups. In Jujube group, mothers used 0.5 mL of Fruit Lotion, and in control group mothers applied 4-5 drops of their breast milk five times a day, after breastfeeding. Both groups were examined on the 7th and 14th days after childbirth. The damage severity was assessed using the Amir scale and the presence or absence of nipple discharge was recorded. A significant difference was observed between the two groups in the extent of nipple damage before intervention on the 3rd day after childbirth and after intervention on the 7th and 14th days after childbirth (P=0.02, P=0.000). No significant difference was observed in sore nipple discharge between the two groups before the study and on the 7th day, while a statistically significant difference was observed between the two groups on the 14th day (P=0.1, P=0.01). The finding of this study revealed that the Zizyphus jujube fruits lotion heals nipple fissure faster and better than breast milk.

The aim of this study was to investigate the effect of Berberis vulgaris (BV) juice consumption on insulin homeostasis, glycemic profiles of patients with benign breast disease (BBD). This parallel design, triple-blind, randomized and placebo controlled clinical trial was conducted on 85 eligible women diagnosed with BBD who recruited from Nour-Nejat hospital, Tabriz, Iran. Participants were randomly allocated into either intervention group who received BV juice (480 mL/day, n=44) or BV juice placebo at the same time (480 mL/day, n=41). After a 7 day run-in period, treatments were administered for the duration of 8 weeks. Participants, care givers and those who assessed laboratory analyses were blinded to the assignments (IRCT registry no: IRCT2012110511335N2). The relative treatment effects of BV supplementation showed decreased serum levels of insulin for 19%, C-peptide for 8%, homeostasis model assessment of insulin resistance index (HOMA-IR) for 16% and glucose to insulin ratio for 22% but HOMA-B increased 44% relative to placebo group over 8 weeks BV supplementation. Although these changes were not statistical significant, the mean changes for C-peptide and HOMA-B were significant just after adjusting for baseline data and covariates. Administration of BV juice showed controlling effects on HOMA related indices, consequently might have beneficial effects on insulin signaling-related functions in women with benign breast tumor.

Memantine, an uncompetitive antagonist of glutamate receptor of the N-methyl-D-aspartate type is approved for the treatment of moderate to severe Alzheimer disease (1). A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia (2). The aim of this study was to examine the efficacy and safety of memantine as an adjunctive treatment for antipsychotics in patient with psychopathology of schizophrenia and schizoaffective. In this study, we assessed the effect of memantine on the pro-inflammatory cytokines such as IL6, TNFa and CRP. In this double-blind, placebo-controlled study, participants were assigned to receive (5-20 mg/day) memantine (n=29) or placebo (n=29), in addition to continuing treatment with antipsychotic for 12 weeks. The primary efficacy measure was the level of pro-inflammatory cytokines (TNFA, IL6, CRP). Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse event (AEs), and measure of extrapyramidal symptoms. At end point, comparison of biomarkers (IL6, TNFα and CRP) in two groups before and after treatment showed a significant decrease of TNFa (P<0.001), but the difference was not significant in CRP and IL6 level (p=0.92 and p=0.77, respectively). The frequency of serious AEs in the memantine vs. placebo group was similar.

Akathisia is a common adverse effect of antipsychotic drugs and is characterized by subjective feelings of restlessness. First-line treatment usually consists of propranolol, a beta adrenergic antagonist. However, propranolol does not seem to be efficacious in up to 70% of patients. This study was aimed to evaluate the effect of vitamin B6 versus propranolol on antipsychotic-induced akathisia (AIA). This study was a comparative, double-blind, randomized trial. In the present study, 66 adult patients with antipsychotic-induced akathisia were enrolled and randomized into three groups, and received vitamin B6 300 mg/12 h or 600 mg/12 h or propranolol 20 mg/12 h. The diagnosis of AIA was made by clinical examination and its severity was assessed by the Barnes Akathisia Rating Scale.Fifty one patients completed 5 days of the trial. The results showed that there was no significant difference in BARS score among the different groups which means that vitamin B6 attenuated the AIA similar to propranolol. However, there wasn’t any significant difference between high or low dose of vitamin B6. In conclusion, the results of this trial suggest that vitamin B6 may be beneficial for ameliorating of antipsychotic-induced akathisia.

Sulfur mustard (SM) is a toxic agent that targets several tissues. It is the leading cause of persistent lung disease, progressive deterioration in lung function, and mortality among injured patients. Disturbed sleep and poor quality of sleep are common in SM-exposed patients with chronic respiratory problems. Melatonin is an alternative medication that has been widely used to treat poor sleep quality caused by several specific conditions. This study aimed to evaluate the efficacy of melatonin administration in improvement of sleep quality in SM-injured patients. In this randomized, double-blind and placebo-controlled trial study a total of 30 SM-exposed male patients were recruited. Patients received 3 mg melatonin (N=15) or placebo (N=15), orally in a single dose, 1 h before bedtime for 56 consecutive days. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnea was determined by STOP-Bang questionnaire. Compared with placebo, melatonin administration significantly improved global PSQI score, particularly sleep latency (P=0.03) and subjective sleep quality (P=0.004). Mean of global PSQI score was declined significantly (P=0.01) from 10.13±3.44 to 6.66±3.08 in melatonin group. No differences in ESS and STOP-Bang scores were observed between two groups. Melatonin was effective in improving global PSQI score and sleep latency, but not daytime sleepiness and obstructive sleep apnea in SM-exposed patients. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Plasma medicine is an innovative and emerging field used in a broad range of medical conditions. The present study focused on consumption and documentation pattern of plasma-derived medicines in a teaching hospital. A two-step study was conducted from October to December 2015. During the first phase, the patient records receiving plasma-derived medicines including Coagulation Factor VIII, IX, Prothrombin Complex Concentrate, Factor VIII/Von Wilber and Complex, Anti-Hepatitis B Immunoglobulin, Intravenous Immunoglobulin, Anti- Tetanus Immunoglobulin, and Albumin were checked to assess recording details of these medications at the time of administration. Adverse events reported with the mentioned products were examined from traceability viewpoint. The second step concentrated on practical strategies to improve documentation status of plasma-derived medicines in the hospital. We proposed national guideline as the first strategy and a new barcoding system to track and identify drug information of plasma medicines. Of the expected drug information, only generic name, dosage from, and strength were recorded after administration. Post-marketing safety surveillance of the plasma products was poor similarly. Unavailability of suitable instructions was the main reason for documentation deficiency. A guideline was designed and implemented to inform healthcare professionals about essentials of appropriate documentation for plasma-derived medicines. Updated results of the ongoing phase will be submitted soon. Our survey highlights the importance of documentation as a key component of plasma-derived medicines surveillance within the hospitals.

This study was aimed at finding the occurrence rate of prescription errors in the outpatients› prescriptions written by faculty and non-faculty physicians practicing in Shiraz, Iran. In this cross-sectional study 2000 outpatient prescriptions were randomly collected from pharmacies affiliated with Shiraz University of Medical Sciences (SUMS) and social security insurance in Shiraz, Iran. Patient information including age, weight, diagnosis and chief complain were recorded. Physicians ‘characteristics were extracted from prescriptions. Prescription errors including errors in spelling, instruction, strength, dosage form and quantity as well as drug-drug interactions and contraindications were identified. The mean ± SD age of patients was 37.91±21.10 years. Most of the patients were male (77.15%) and 81.50% of patients were adults. The average total number of drugs per prescription was 3.19±1.60. The mean ± SD of prescription errors was 7.38±4.06. Spelling error (26.4%), instruction error (21.03%), and strength error (19.18%) were the most frequent prescription errors. The mean ± SD of prescription errors was 7.83±4.2 and 6.93±3.88 in non-faculty and faculty physicians, respectively (P<0.05). Number of prescription errors increased significantly as the number of prescribed drugs increased. All prescriptions had at least one error. The rate of prescription errors was higher in non-faculty physicians. Number of prescription errors related with the prescribed drugs in the prescription.

Medication interactions are associated with various unwanted adverse drug reactions. Medication Reconciliation involves a process in which a complete list of patient's previously prescribed medications are recorded and subsequently evaluated within the context of concomitantly prescribed medications and present medical condition during the hospitalization. Medical records of randomly selected 270 patients hospitalized in internal medicine, cardiovascular and infectious diseases wards were evaluated. Drug interactions were checked by LexiCompÒ database. Each interaction was assigned a risk rating of A, B, C, D, or X. The progression from A to X was based on increased urgency for responding to the data. Completed reconciliation forms were attached to patient charts for evaluation of physicians' compliance. Drug interactions were observed in 65.2% (176/270) of cases. The risk rating of interactions was categorized as C, D and X in 54.2%, 32.4%, and 13.4% of cases, respectively. There was a positive correlation between the number of prescribed medications and the rate of interactions (p -value<0.001, Kendall's correlation coefficient=0.487). Moreover, the length of hospitalization and the rate of drug interactions were significantly correlated (p -value<0.001, Kendall's correlation coefficient=0.350). Cardiovascular agents constituted the largest proportion of interactions (25%) followed by antibiotics (18%) and immunosuppressive agents (6%). In 59.6% of cases, no corrective action was taken by the physicians. Medication discrepancies occur commonly in hospital settings. Structured medication reconciliation may have a positive impact on prevention of medication errors.

Nowadays pharmacists should be involved in patients care and providing pharmaceutical care more than before, but still there is a gap between standard of care and pharmacy practice in pharmacies. In this study we aimed at evaluating the pharmacists experiences and attitudes about ethical professional practice in pharmacies. The study was conducted in the Tehran University of Medical Sciences, Tehran, Iran.This study performed as a mixed method study including 12 semi-structured interviews and two focus group discussions (FGDs). All interviews and FGDs were recorded verbatim. The study evaluates the pharmacy practice based on the Code of Ethics for National Pharmaceutical System requirements.Our study presents the pharmacists ethical challenges in 14 areas of practice such as lack of proper pharmacists-patients and inter and intra-professional relationship; poor management of medication error; lack of pharmacists awareness about their responsibilities, professional rules and regulations; non-OTC drug dispensing without prescription; no collaboration with custodian organizations; dissatisfaction from profession; financial problems; mismanagement in confronting with ads and offers of pharmaceutical companies, and conflict of interest; and uneven drug distribution during shortage.For providing standard pharmaceutical care modification of infra structures, educational system and regulations in pharmaceutical system is highly recommended.