The estimation of pharmacokinetics and pharmacodynamics of drugs used in the leukaemia multidrug therapy is of great importance. The multidrug therapy of high effectiveness carries the risk of side effects and an increase of therapeutic action of free fractions of drugs. This can be dangerous when exhibiting toxic effect. Regulation of cysteine proteinases and their inhibitors are of utmost importance in diseases like lung cancer, chronic inflammatory conditions such as asthma, emphysema, and idiopathic pulmonary fibrosis. Protease-antiprotease imbalance accelerates disease progression. In the present study, Thiol Protease inhibitors was purified from Lungs using simple and efficient chromatographic techniques. Further, the effect of methotrexate (MTX) (an antineoplastic and antirheumatic) drug on lung cystatin was studied to explore the drug induced protein dysfunction. In addition, we have studied the effect of free radicals on thiol protease inhibitors and their preventive measurement by Polyphenols like Curcumin and Quercetin. Finally we have reported the toxicity of Cigarette smoke on thiol protease inhibitors implicated in cardiovascular disease and Emphysema.