Efficacy, Safety and Tolerability of Valsartan and Hydrochlorothiazide Compared to Valsartan and Amlodipine in Stage 2 Hypertension

Background: Hypertension is a growing medical and public health issue. The United States and European treatment guidelines have been issued to attain smooth control of hypertension in various categories of patients. It is a need of time to unveil safe combination therapies in various populations. Objectives: (i) To determine the efficacy of valsartan and hydrochlorothiazide versus valsartan and amlodipine (ii) To determine the safety and tolerability of both combinations. Materials & Methods: This experimental study was conducted at Shalamar Hospital Lahore. 126 patients with stage 2 hypertension were recruited from the medical outdoor of Shalamar Hospital Lahore after getting informed consent. In group A, 63 patients were given valsartan and hydrochlorothiazide. In group B, 63 patients were given valsartan and amlodipine. Blood pressure (BP) of both study groups was recorded on day zero, 2nd, 4th, and 8th weeks and the readings were entered on a Proforma. The efficacy of drug combinations was accessed in both groups by recording the change in mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP). The safety and tolerability of the drug combinations were assessed in terms of side effects and laboratory findings. Results: In group A, there was a 39±7mmzHg and 18±1mmHg decrease in MSBP and MDBP, respectively, from baseline BP. In group B, there was a 26.7±4mmHg and 14±2 mmHg decrease in MSBP and MDBP, respectively, from baseline BP. Both combinations were safe, and no significant difference in the efficacy of both combinations was observed after 8-week of treatment. Conclusion: Both combinations are effective for control of BP, but the valsartan and hydrochlorothiazide combination (group A) appears to have better tolerability and greater effect in decreasing BP as compared to the combination of valsartan and amlodipine (group B), although this difference is not statistically significant.  

Phytochemical Investigation on the Chemical Constituents of Caralluma Flava

The research work embodied in this thesis deals with the isolation of chemical constituents from the Omani plant named Caralluma flava (N.E.Br) Meve & Liede along with the spectral characterization, biological activities and computational studies. Crude crystals (CR) obtained from the squeezed sap of succulent C. flava showed significant anticancer activity against MDA-MB-231 breast cancer cells and provided nine new pregnane glycosides namely Desmiflavaside A (1), Desmiflavaside B (2), Desmiflavaside C (3), Desmiflavaside D (4), Nizwaside (5), Desflavaside A (6), Desflavaside B (7), Desflavaside C (8) and Desflavaside D (9). The structures of these isolates were elucidated through spectral analysis using UV, IR, HRSEIMS, NMR and by comparing with literature reports. Treatment of MDA-MB-231 breast cancer and SKOV-3 ovarian cancer cells with compounds 3-5 demonstrated a prominent reduction in the viability of both types of cancer cells. Furthermore, 3-5 were also tested for their effect on normal breast epithelial cells (MCF-10-2A) which displayed no significant cytotoxicity on normal cells. The molecular docking studies of 3-5 revealed that these molecules have a good potential to bind with the target protein tyrosine phosphatase. The methanolic extract (ME) of squeezed residual plant and its different fractions also showed good anticancer activity against MDA-MB-231 cells. Different fractions of ME, CR and compounds (1-5) were additionally evaluated for enzyme inhibition (urease, acetylcholinesterase and α-glucosidase) and DPPH antioxidant activities which displayed no remarkable results. The research work embodied in this dissertation has resulted four publications as mentioned in the end of the thesis.