Comparison of Effect of Leukotriene Biosynthesis Blockers and Inhibitors of Phosphodiesterase Enzyme in Patients with Bronchial Hyperreactivity

Abstract

Aim: Blocking effect of leukotriene biosynthesis-zileuton and blocking the effect of phosphodiesterase enzyme-diprophylline in the treatment of patients with bronchial asthma and bronchial increased reactivity, and tiotropium bromide as an antagonist of the muscarinic receptor studied in this work.

Methods: Parameters of the lung function are determined with Body plethysmography. The resistance of the airways (Raw) was registered and measured was intrathoracic gas volume (ITGV), and specific resistance (SRaw) was also calculated. For the research, administered was zileuton (tabl. 600 mg) and diprophylline (tabl. 150 mg).

Results: Two days after in-house administration of leukotriene biosynthesis blocker-zileuton (4 x 600 mg orally), on the day 3 initial values of patients measured and afterwards administered 1 tablet of zileuton, and again measured was Raw and ITGV, after 60, 90 and 120 min. and calculated was SRaw; (p < 0.01). Diprophylline administered 7 days at home in a dose of (2 x 150 mg orally), on the day 8 to same patients administered 1 tablet of diprophylline, and performed measurements of Raw, ITGV, after 60, 90 and 120 min, and calculated the SRaw (p < 0.05). Treatment of the control group with tiotropium bromide - antagonist of the muscarinic receptor (2 inh. x 0.18 mcg), is effective in removal of the increased bronchomotor tonus, by also causing the significant decrease of the resistance (Raw), respectively of the specific resistance (SRaw), (p < 0.05).

Conclusion: Effect of zileuton in blocking of leukotriene biosynthesis is not immediate after oral administration, but the effect seen on the third day of cys-LTs' inhibition, and leukotriene B4 (LTB4) and A4 (LTA4) in patients with bronchial reactivity and bronchial asthma, which is expressed with a high significance, (p < 0.01). Blockage of phosphodiesterase enzyme-diprophylline decreases the bronchial reactivity, which is expressed with a moderate significance, (p < 0.05).

Keywords: Bronchial asthma; Diprophylline and tiotropium bromide; Zileuton.

Figure 1

Effect of zileuton (p < 0.01), (2 x 600 mg, tablet), and tiotropium bromide (p < 0.05), (2 inh. x 18 mcg); in Raw, ITGV and SRaw. 2 days after in-house administration of zileuton (4 x 600 mg); (n = 7; X ± SEM)

Figure 2

Effect of diprophylline (p < 0.05), (2 x 150 mg, tablet), and tiotropium bromide (p < 0.05), (2 inh. x 18 mcg); in Raw, ITGV and SRaw. 2 days after in-house administration of diprophylline (n = 7; X ± SEM)