Leflunomide (LF) represents the prototype member of dihydroorotate dehydrogenase (DHODH) enzyme inhibitors. DHODH is a mitochondrial inner membrane enzyme responsible for catalytic conversion of dihydroorotate into orotate, a rate-limiting step in the de novo synthesis of the pyrimidine nucleotides. LF produces cellular depletion of pyrimidine nucleotides required for cell growth and proliferation. Based on the affected cells the outcome can be attainable as immunosuppression, antiproliferative, and/or the recently gained attention of the antiviral potentials of LF and its new congeners. Also, protein tyrosine kinase inhibition is an additional mechanistic benefit of LF, which inhibits immunological events such as cellular expansion and immunoglobulin production with an enhanced release of immunosuppressant cytokines. LF is approved for the treatment of autoimmune arthritis of rheumatoid and psoriatic pathogenesis. Also, LF has been used off-label for the treatment of relapsing-remitting multiple sclerosis. However, LF antiviral activity is repurposed and under investigation with related compounds under a phase-I trial as a SARS CoV-2 antiviral in cases with COVID-19. Despite success in improving patients’ mobility and reducing joint destruction, reported events of LF-induced liver injury necessitated regulatory precautions. LF should not be used in patients with hepatic impairment or in combination with drugs elaborating a burden on the liver without regular monitoring of liver enzymes and serum bilirubin as safety biomarkers. This study aims to review the pharmacological and safety profile of LF with a focus on the LF-induced hepatic injury from the perspective of pathophysiology and possible protective agents.

IntroductionWorldwide, thyroid diseases are among the most prevalent endocrine disorders. According to the Saudi Arabian Ministry of Health (MOH), many thyroid disease cases remain undiagnosed and, as a result, are not treated because the patient has no symptoms or is unaware of them. Hence, this study aims to assess the knowledge about hypothyroidism and hyperthyroidism among Saudi Arabia's population. MethodologyA cross-sectional survey was conducted among Saudi adults in five randomly selected regions in Saudi Arabia from December 2022 -January 2023. An Arabic self-administered questionnaire was sent to randomly selected participants via an online link. The questionnaire was composed of four parts: Sociodemographic; knowledge related to hypothyroidism and hyperthyroidism diseases and their differences; knowledge about the thyroid gland in terms of functions and causes of thyroid dysfunction. The Statistical Package for Social Sciences was used for data analysis. ResultsOut of 996 participants (66.2% women), 70.1% knew the function of the thyroid gland, 66.4% knew that women are more susceptible to thyroid disease, and 49.5% knew the association between thyroid dysfunction and heart disease. Female sex, higher education, and old age were associated with good knowledge, and no differences were evident regarding nationality and residence. The results showed inadequate awareness regarding thyroid diseases in Saudi Arabia, with some parts of this population being very clearly below average. ConclusionKnowledge regarding thyroid disorders was sub-optimal in Saudi Arabia; older women with higher education had the best knowledge. With even larger samples, we recommend that future studies be made to develop clear and decisive public health strategies that can be implemented at once.