Evaluation of anti-inflammatory and immunomodulatory potential of Lawsone (2-hydroxy-1,4-naphthoquinone) using pre-clinical rodent model of rheumatoid arthritis.

Background: Lawsone (2-hydroxy-1,4-naphthoquinone) is naturally present in Lawsonia Inermis and flowers of Eicchornia crassipes. This study assessed the anti-arthritic potential of Lawsone, using FCA-induced Sprague-Dawley rats. Methods: Arthritic progress was analyzed through a macroscopic scoring scale, measurement of paw edema, and histopathological changes. Effects of Lawsone on mRNA expression levels of inflammatory markers were examined using the reverse transcription PCR technique. ELISA technique was used to evaluate the PGE2 levels. Moreover, levels of biochemical and hematological parameters were also analyzed. Results: The research elucidated that Lawsone showed an inhibitory potential towards arthritic progress and ameliorated the paw edema. The histopathological analysis also validated the inhibition in arthritic development. Treatment with Lawosne reduced the expression levels of inflammatory markers in rats i.e., VEGF, TNF-α, MMP-2, MMP-3, NF-κB, IL-1ß, and IL-6. PGE2 levels (all p < 0.001) were also found reduced in treatment groups. Lab investigations showed improved results of hematological and hepatic parameters in the treated groups as compared to the positive control. This study found no hepatotoxic or nephrotoxic effects of Lawsone in the test doses. Conclusion: Lawsone possesses an anti-arthritic property which could be ascribed to its immunomodulatory and anti-inflammatory effects.

Correct administration aid for oral liquid medicines: Is a household spoon the right choice?

Background: Correct medicine dosing is an important component in the safe and effective delivery of medicines, particularly for the pediatric population. However, there is a scarcity of public campaigns on the correct administration and choice of dosing aids for oral liquid dosage form in many countries, leading to medicine safety issues and therapeutic failures. Methods: The study targeted the assessment of the knowledge and practice of university students. It utilizes pre- and post-intervention surveys administered through google forms as a survey tool during online zoom and in-person sessions. The intervention included a short video presentation detailing the selection and use of medicine spoons and other aids for the administration of oral liquid dosage. The Fischer Exact test was used to assess the pre- and post-test shift of responses. Results: Nine-degree programs were engaged in the activity, and 108 students attended this health awareness activity after obtaining formal consent. A significant decline (CI = 95%, **** p-value < 0.05) in the choice of selecting tablespoon and a shift to a low-volume spoon, as well as rejection of an entire variety of household spoons, were observed. A significant improvement in the correct naming of spoons, the meaning of the abbreviation "tsp," and the correct volume of a standard teaspoon were also observed with a p-value of <0.001. Conclusion: A deficit in the knowledge of the proper use of measuring devices for oral liquid medicines in the educated population was observed, which can be enhanced through simple tools like short video presentations and awareness seminars.

Availability of Access, Watch, and Reserve groups of essential antibiotics: a cross-sectional survey.

Background: Lower-middle income countries face drastic challenges in Access to essential medicines. Data regarding Pakistan is scarce with no comprehensive study in this regard. The objectives of the study are to document and compare public and private sector availability of all essential antibiotics as well as to conduct a comparison among the AWaRe groups. Methods: The study analyzed 103 essential antibiotics comprising 51 Access, 29 Watch, 6 Reserve, and 17 anti-tuberculosis drugs from 15th August to 10th September 2020 in Lahore, Pakistan. It included on-spot physical availability and availability trend surveys. The survey sites included five public tertiary care hospitals with one as anchor and four randomly selected. Their hospital pharmacies and one randomly selected private retail pharmacy from the vicinity each hospital comprised the ten sampling sites. Percentage availability for each antibiotic was categorized as high (>80%), fairly high (50-80%), low (30-<50%), very low (<30->0%), and not available (0%). Results: The mean percentage on-spot availability was 23.76% ± 5.19 (14-25%) for public facilities and 59.20% ± 4.45 (54-66%) for private sector retail pharmacies. The overall percentage of available essential antibiotics varied significantly (p** < 0.001) in public and private sector sampling sites. Except for the Watch group, all other groups showed the mode of 0% availability. A significant difference (p**** < 0.00001) was seen in percentage availability by Access, Watch, Reserve, and anti-TB-all groups of essential antibiotics. The availability trend survey revealed a list of 18 medicines as 'as never been available', and five medicines were 'not available for 5 years or more than 5 years.' Fourteen medicines as 'never been heard.' Conclusion: Non-availability of essential medicines is a significant public health challenge at public-sector facilities in Pakistan. It was observed that a number of essential antibiotics were not available in both public and private sectors. A number of corrective strategies are required. This includes the engagement of stakeholder and government bodies. This can help to improve supply chain barriers.

Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan.

Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan. Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration-time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks. Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively. Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.

Availability of essential medicines in Pakistan-A comprehensive document analysis.

INTRODUCTION: Access to essential medicines (EMs) is a basic human right. Non-availability and shortages of EMs are reported for Pakistan but there is insufficient data to define the nature and magnitude of this problem. The current study is designed to systematically analyze the medicines included in the National Essential Medicines List (NEML) for their availability through comprehensive document analysis. METHODS: An expanded list of medicinal items was developed using the NEML of Pakistan (2018) to enlist individual medicines with their specifications. Registration status of the medicines was searched using three publicly accessible information sources; Pharmaguide 25th Edition, 2018-19, the on-line Drug Information System, and the Mobile Application Pharmapedia followed by a later 3-step validation of the data. The unregistered EMs were then further categorized into three subgroups in accordance with their possible remedial strategies. FINDINGS: The 19 studied categories comprised 690 EMs and it was found that 179 (26%) of these EMs don not have a registration status. However, it was also identified that the availability of 47 (26.2%) out of 179 unregistered EMs can be enssured by strengthening compounding services, and prioritizing registration of age-appropriate formulations. Availability of another 39 (21.7%) such medicines can be ensured by revising the NEML or the product registrations for the slight differences in their different specifications. The categories showing high proportion of unregistered medicines included anti-Parkinson's medicines (100%), antidotes and other substances used in poisoning (60%), diuretics (47%), anticonvulsants/antiepileptics (42%), hormones and other endocrine medicines and contraceptives (38%), medicines for mental and behavioral disorders (30%), anti-infectives (27%), medicines for pain and palliative care (26%), medicines for neonatal care (25%), medicines for diseases of joint (25%), gastrointestinal medicines (24%) and cardiovascular medicines (15%). CONCLUSION: The study shows the absence of registration status of a significant number of EMs in Pakistan. This could be major barrier in their access. Strategies are needed to strengthen the processes of their registration on priority basis.