JNTU B.Pharmacy III PHARMACOLOGY-III Previous Question Paper (November/December - 2020 - R17)

Corticosteroids exert their effects primarily by binding to glucocorticoid receptors (GR) in the cytoplasm. Upon binding, the receptor-ligand complex translocates to the nucleus, where it interacts with glucocorticoid response elements (GREs) in the promoter regions of target genes. This leads to the upregulation of anti-inflammatory proteins (like lipocortin-1) and the downregulation of pro-inflammatory cytokines (such as IL-1, IL-6, and TNF-alpha). They also inhibit the enzyme phospholipase A2, thereby preventing the release of arachidonic acid and the subsequent synthesis of prostaglandins and leukotrienes.

Adverse effects include: metabolic disturbances such as hyperglycemia, weight gain, and muscle wasting; increased susceptibility to infections due to immunosuppression; osteoporosis and growth retardation in children; skin thinning and delayed wound healing; psychiatric disturbances; and the risk of adrenal insufficiency upon abrupt withdrawal due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Montelukast is a selective and orally active leukotriene receptor antagonist (LTRA). It specifically binds with high affinity and selectivity to the CysLT1 receptor, which is found in human airway smooth muscle and macrophages.

By blocking the binding of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) to these receptors, montelukast inhibits the physiological actions of these potent inflammatory mediators. This prevents leukotriene-induced bronchoconstriction, airway edema, mucus secretion, and the recruitment of eosinophils into the airways. Consequently, it effectively reduces airway inflammation and improves lung function in patients with asthma and allergic rhinitis.