ABSTRACT
Objective: To observe two drugs [captopril and imidapril] action on smooth muscle tone of trachea and to facilitate safe and rational use of ACE inhibitors, particularly in patients with chronic obstructive airway disease
Study Design: Comparative controlled in-vitro experimental Study
Place and Duration of Study: This study was conducted at the Pharmacology Department, Army Medical College, Rawalpindi from December 2012 to May 2013
Materials and Method: First the effect of bradykinin acetate on the smooth muscle of trachea has been observed. Cumulative concentration-effect relationship was studied with different concentrations of bradykinin on the smooth muscle starting with 22 micro g to 132 micro g/dl. The method was done again with captopril 10[-5] M concentration and imidapril 10[-5] M respectively. In second set of experiments cumulative concentration-response curves were prepared by increasing concentrations of captopril and imidapril separately with fixed concentration of bradykinin 66 micro g/dl
Results: Dose related vacillating contraction of smooth muscle of trachea is produced by bradykinin. The average value of effect received with 132 micro g/dl of bradykinin in the presence of captopril was 51.33 +/- 2.79 and in the presence of imidapril was 25 +/- 7.26. All these ACE inhibitors displaced the concentration effect curves of bradykinin to left and upward. On comparison among themselves it was observed that imidapril produced least enhancement of tracheal contraction. Similar results were produced by second set of experiments
Conclusion: Imidapril is found to cause least enhancement of contraction caused by bradykinin on tracheal muscle. Further clinical trials may be conducted to establish the differential effects of various clinically used ACE inhibitors on the respiratory passages in hypertensive patients concomitantly suffering from COAD
ABSTRACT
Objective: To compare the inhibitory effects of Glibenclamide and Repaglinide on loperamide induced relaxation of isolated ileum of Rabbit. Study Design: Comparative controlled in-vitro experimental Study. Place and Duration of Study: This study was conducted at Department of Pharmacology, Yusra Medical and Dental College Islamabad from February to April 2014. Materials and Methods: Isolated pieces of small intestine of rabbits placed in freshly prepared Tyrode nutritional solution. Six groups were designed. In group I, effect of Acetylcholine on the intestine was observed. In group I1 ileum was exposed to serial dilutions of acetyl choline in the presence of fixed concentration of loperamide dose response curve was plotted. In group 111 fixed dose of Glibenclamide 1u6 was given and dose response curve was plotted with Acetylcholine. In group IV fixed dose of Repaglinide was given and dose response curve was lotted with Acetylcholine. Group V was given Loperamidffilibenclamide and dose responce curve was plotted with Acetylcholine, while group VI was given Loperamide+Repaglinide and dose response curve was plotted with Acetylcholine. The effects were observed and recorded on Power lab. Results: Acetyl choline has produced dose dependent increase in force of contraction from 4.9 to 7.2 mN. In the presence of glibenclamide the force of intestinal smooth muscle contraction increase from 6.4 to 7.8mN and in the presence of loperamide the force decreased from 4.8 to 3.03mN. In the end effect observed with acetyl choline in the presence of loperamide and glibenclamide is 6.5 to 7.7mN. Similarly with repaglinide alone the force of contraction increased from 5.4 to 9.6mN and with repaglindie + loperamide from 4.3 to 21.5 mN. On statistical analysis 't' test as applied and P value was found to be significant that is PK0.05. The dose response curve of acetylcholine on intestinal smooth muscle of rabbit shifted towards left side with glibenclarnide and rapaglinide alone. In the presence of Loperamide the curve shifted towards right side. Glibenclamide and repaglinide when given together with loperamide respectively lead to leftwards shift of the dose response curve. Conclusion: Hence sulfonylurea glibenclamide and repaglinide, the oral anti-diabetics effectively reversed the relaxation of intestinal smooth muscle by loperamide