Effectiveness and Properties of Hydrazide Drugs that Inhibit Growth of Mycobacterium tuberculosis | Chapter 12 | Modern Advances in Pharmaceutical Research Vol. 2

Aims: To examine the properties of hydrazide compounds shown to inhibit Mycobacterium tuberculosis. To identify properties that affect efficiency of bacterial inhibition.

Study Design: Utilizing data from previous studies of compounds that inhibit Mycobacterium tuberculosis, then statistical and pattern recognition methods are applied to identify interrelationships.

Place and Duration of Study: Department of Chemistry, Durham Science Center, University of Nebraska at Omaha, from January 2016 to July 2016.

Methodology: Interrelationships of pharmacological properties were identified by use of various pattern recognition techniques, such as hierarchical cluster analysis and path analysis. Molecular properties and descriptors for all compounds were determined, with additional characteristics such as structure scaffolding and functional group position was accomplished. Statistical analysis, including Pearson r correlation, Mann-Whitney test, one-way ANOVA, Kruskal-Wallis, and descriptive statistics were determined. Multiple regression analysis of molecular property values allows prediction of similar compounds. Determination of any numerical outliers was accomplished by applying Grubb’s test.                                                                                                    

Results: Compounds inhibiting the growth of Mycobacterium tuberculosis contained an aromatic ring or were non-aromatic structures (no ring). There was weak negative correlation of MIC to formula weight. The average formula weight, polar surface area, and Log P, is 183.55 grams/mole, 63.70 A2, and 0.768, respectively. Values of MIC ranged from 14.7 µg/mL to 100 µg/mL. Extent of bacterial inhibition was similar between aromatics to non-aromatics. No outliers were identified by Grubb’s test for all values of MIC taken together. Path analysis showed polar surface area to have most effect on MIC.

Conclusion: The measured level of growth inhibition MIC, showed strong positive relationship to polar surface area, number of hydroxyl and amine groups, oxygen and nitrogen atoms. Two aromatic compounds having a pyridine ring were found to be most similar to isoniazid. Aromatic and non-aromatic compounds showed similar levels of bacterial inhibition overall.

Author(s) Details

Dr. Ronald Bartzatt
Durham Science Center, University of Nebraska, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

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Prodrugs Design | Chapter 11 | Modern Advances in Pharmaceutical Research Vol. 2

Prodrug design can be used in the following cases: improving active drug solubility and consequently bioavailability, increasing permeability and absorption and modifying the drug’s distribution profile. In the prodrug design, a computational approach consisting of calculations using Molecular Orbital (MO) and Molecular Mechanics (MM) methods and correlations between experimental and calculated values can be utilized.

Author(s) Details

Professor Rafik Karaman
Department of Bioorganic Chemistry, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine and Department of Sciences, University of Basilicata, Viadell’Ateneo Lucano 10, 85100, Potenza, Italy.

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Role and Effectiveness of Simulation-based Training in Raising Family Medicine Residents’ Clinical Resuscitation and Critical Care Skills | Chapter 10 | Modern Advances in Pharmaceutical Research Vol. 2

Background: Family medicine (FM) physicians are bound to providing healthcare services at a variety of clinical and community settings. They should be equipped to competently handle health emergencies in a multitude of professional procedures. Medical education on patients often raises safety issues; simulation-based medical education (SBME) was a solution enabling education in a risk free environment.

Aim: To analyze the impact of a SBME on Family medicine residents’ performance in critical resuscitation procedures.

Methods: A systematic review of published articles between 1996 and 2016 was conducted. Systematized literature search through ranked search engines was done. All original research articles on SBME published between 1997 and 2012 were examined.

Results: The analysis included 6 relevant studies selected. The studies’ venues included either academic or healthcare settings in Netherlands, Switzerland; Greece, and Canada. The studies’ populations were mainly family medicine, and general practitioner, residents who participated in simulated resuscitation/life support educational activities. The number of participants in each SBME activity ranged between 28 and 72. The study of the Greek experiment included 434 residents. An interventional design was advocated, and a self-reported questionnaire to evaluate participants’ skills pursuant to SBME activities before and/or after the learning activities was unanimously utilized. The main SBME focus involved patient resuscitation and critical event care. Most studies came to significantly positive conclusions about SBME in raising residents’ resuscitation knowledge, skill, and behavior.

Conclusions: The role of interactive SBM teaching in preparing FM residents to rescuing and resuscitating the critically ill independently is now sufficiently evident. Despite such success potential, methods to achieve improved critical care competence advocating low cost simulated medical education solutions in low economic circumstances should be sought.

Author(s) Details

Dr. Majed Kh. Al Harthi
Department of Family and Community Medicine, Medical Education Fellowship, University of Toronto, Canada.

Raouf M. Afifi (MD, PhD, MSc, MPH, MHA, FACHCE)
Community Health Research Institute, International Management-Health Services, Indianapolis, Indiana, USA and National Research Excellence Institute, Cairo, Egypt.

Dr. Mohamed A. Tashkandi
Department of Preventive Medicine, Directorate of Health Affairs, Makkah, MoH, Kingdom of Saudi Arabia.

Dr. Ashraf E. Saad (MBBS, MPH, CIC)
Department of Preventive Medicine, Armed Forces Hospital, Wadi Al-Dawasir, Kingdom of Saudi Arabia.

Yousef Afifi
Community Health Research Institute, International Management-Health Services, Indianapolis, Indiana, USA and National Research Excellence Institute, Cairo, Egypt.

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Spectrum of Thyroid Diseases in Makurdi, Benue State of Nigeria: A Review of 94 Consecutive Cases | Chapter 09 | Modern Advances in Pharmaceutical Research Vol. 2

This study aims to review the spectrum of thyroid diseases in Makurdi, Benue State of Nigeria through a histopathological survey. It is a retrospective study covering 1st January, 2005 to 31st December, 2016.


Ninety four (94) consecutive cases of thyroidectomy specimens collected from Holy Trinity Specialist Hospital, Makurdi, Nigeria a private hospital and Benue State University Teaching Hospital, Makurdi, Nigeria between January 1st, 2005 to December 31st, 2016 were examined histologically and analyzed with regards to age and sex.


There were 7 male specimens as against 87 female specimens giving a male: female ratio of 1:12.43. Nodular colloid goiter was the commonest histological lesion accounting for 72%, followed by thyroid carcinoma which accounted for 11.66%, adenoma 10.60%. Thyroiditis, 5.30% was the fourth commonest pathology and thyroglossal cyst/duct accounted for 1.06%. Follicular carcinoma was the commonest malignancy seen accounting for 7.51% of all specimens and most occurred in females. However, most of these thyroid malignancies occurred in younger age groups (20-49years) compared to other studies in Nigeria and Africa. There is need for a large scale study in Makurdi on the relatively younger age of our thyroid malignancies, higher incidence of follicular carcinoma when compared to other African studies and the relatively high incident of thyroiditis found in this study
.

Author(s) Details

B. A. Eke
Department of Surgery, College of Health Sciences, Benue State University, Makurdi, Benue State, Nigeria.

B. A. Ojo
Department of Anatomic Pathology, College of Health Sciences, Benue State University, Makurdi, Benue State, Nigeria.

A. Adekwu
Department of Surgery, College of Health Sciences, Benue State University, Makurdi, Benue State, Nigeria.

M. Efu
Department of Anaesthesia, College of Health Science, Benue State University, Makurdi, Benue State, Nigeria.

E. I. Ogwuche
Department of Surgery, College of Health Sciences, Benue State University, Makurdi, Benue State, Nigeria.

P. Abayol
Department of Surgery, Federal Medical Center, Makurdi, Benue State, Nigeria.

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TNF-α Inhibitor Treatment for Crohn’s Disease: Comparative Review of Post Therapy Malignancy between Infliximab and Adalimumab | Chapter 08 | Modern Advances in Pharmaceutical Research Vol. 2

The association between chronic inflammatory disease and cancer has been well established through years of research. In corollary, progressive resistance to chimeric monoclonal antibodies has been reported in literature. The purpose of this investigation was to establish the overall trend of the chimeric monoclonal antibody (Infliximab) failure compared with human monoclonal antibody (Adalimumab). It was opined that this failure may result in subclinical yet cancer-inducing inflammation that could be measurable in patient populations undergoing the therapy by examining cancer prevalence. An overall trend of increased incidence of new malignancy in patient populations on Infliximab compared with Adalimumab was confirmed from the literature reviewed. There was also a significant trend of developing Gastrointestinal (GI) related cancer in patients on Infliximab, which corresponds with the majority of the progression process in Crohn’s disease. It was opined that future observations in clinical practice will lead to the phasing out of Infliximab as a front-line monoclonal antibody in the treatment of Crohn’s disease in favor of less immunogenic monoclonal antibodies. In conclusion an increased incidence of both general and GI malignancies has been widely reported in patient populations undergoing Infliximab therapy than with Adalimumab.

Author(s) Details

Danil Hammoudi, MD
Department of Pathology, Saint James School of Medicine, BWI, Anguilla.

Adekunle Sanyaolu, PhD
Department of Medical Microbiology and Immunology, Saint James School of Medicine, BWI, Anguilla

Nirav Nagarsheth, MD, MBA
Department of Pathology, Saint James School of Medicine, BWI, Anguilla.

Jason Kimbel, M.D., MHA
Department of Pathology, Saint James School of Medicine, BWI, Anguilla.

Amos Abioye, PhD
Department of Pharmacy, Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, United Kingdom.

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The Question of Prodrug Naming | Chapter 07 | Modern Advances in Pharmaceutical Research Vol. 2

Prodrug is a term used to define a pharmacologically inactive chemical entity that can be used to temporarily alter the physicochemical properties of a drug to increase its usefulness and decrease its associated toxicity. According to the definition, the inactive prodrug converts to its active parent drug and a non-toxic linker upon exposure to a physiological environment. Albert stated in his Selective Toxicity book, that the term prodrug is incorrect and should be replaced with the term predug. He apologized for having invented the term, however, now it is too widely used to alter.

Author(s) Details

Professor Rafik Karaman
Department of Bioorganic Chemistry, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine and Department of Sciences, University of Basilicata, Viadell’Ateneo Lucano 10, 85100, Potenza, Italy.

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Pharmacological Profile and Indications of Non-Vitamin K Antagonist Oral Anticoagulants: Updated Review | Chapter 06 | Modern Advances in Pharmaceutical Research Vol. 2

The non-vitamin K antagonist oral anticoagulants have been approved since 2008 for the prevention of systemic embolism and stroke in patients with non-valvular atrial fibrillation with prior stroke, transient ischemic attack, or CHA2DS2-VASc score ≥2. According to the latest guidelines, if CHA2DS2-VASc score ≥2 for all male patients or if CHA2DS2-VASc score ≥3 for all female patients, oral anticoagulants are recommended, and considering shared decision between doctor and patient. However, they are contraindicated in patients with mechanical prosthetic valve and in patients with moderate-to-severe mitral stenosis and atrial fibrillation. They have also been approved for prevention and treatment of deep vein thrombosis and pulmonary embolism. Dabigatran, a direct thrombin inhibitor, was the first to be approved, followed by the factor Xa inhibitors, rivaroxaban, apixaban, and in 2015, edoxaban. They have advantages such as the use of fixed-dose, with infrequent drug interaction, rapid onset of action and do not require monitoring of their anticoagulant action. Nonetheless, they have different half-lives, the need for dose adjustment according to renal function, weight and age of the patient. Its use in pregnant women and children or adolescents is not well established. There are also peculiarities about the risks of bleeding, effects on coagulation tests and specific antidotes. Through this review we discuss the pharmacokinetics and pharmacodynamics characteristics of direct oral anticoagulants, its indications, interactions and contraindications. Analysis of its efficacy, safety, risk-benefit ratio and costs will also be addressed.

Author(s) Details

Rose Mary Ferreira Lisboa da Silva
Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Brazil.

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Prodrugs Designed by DFT and Molecular Mechanics Methods | Chapter 05 | Modern Advances in Pharmaceutical Research Vol. 2

The accumulation of knowledge on intramolecular processes, enzymes and transporters along with the vast progress in molecular revolution have accelerated the search for prodrugs having the capability to replace their corresponding current marketed drugs and to provide therapeutics with better pharmacological profiles. Utilizing the different available computational methods has led to the design and synthesis of a variety of prodrugs to replace their corresponding parent drugs.

It has been proven that prodrugs can significantly improve the life quality of patients.

The directed enzyme prodrug therapy (DEPT) approach to employ the design of artificial enzymes to activate prodrugs at specific sites along with use of intramolecular processes to design prodrugs are the most attractive strategies to obtain more efficient therapeutics.

Author(s) Details

Professor Rafik Karaman
Department  of  Bioorganic  Chemistry,  Faculty  of  Pharmacy,  Al-Quds  University,  P.O.Box  20002,  Jerusalem,  Palestine and Department of Sciences, University of Basilicata, Via dell’ateneo Lucano 10, 85100, Potenza, Italy.

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In vitro and ex vivo Studies of Nonionic Surfactant Vesicles Using 23 Factorial Design: Metoprolol Tartrate Used as Model Drug | Chapter 04 | Modern Advances in Pharmaceutical Research Vol. 2

The purpose of this study was to formulate and investigate metoprolol tartrate (MT) loaded non-ionic surfactant vesicles using 23 factorial designs. Preparation of niosomal drug delivery of MT increased its bioavailability which led to being better therapeutic effects, reduced the frequency of dosing and decreased side effects of hypertensive patients. Ether injection method (EIM) and thin film hydration method (TFHM) were used for the preparation of all formulations as per full factorial design to study the effect of two independent variables X1 (amount of span-60), and X2 (amount of cholesterol) on three dependent variable Y1 (percent drug entrapment efficiency), Y2 (percent drug content) and Y3 (percent cumulative drug release) respectively. The relation between the dependent and independent variables was drawn out from the mathematical equation and response surface methodology (RSM). Statistical analysis was performed using ANOVA. Microscopic observation confirmed that all particles were uniform in size and shape. The particle size of niosomes measured by SEM was between 3 μm to 4.5 μm that given the evidence of large uni-lamellar vesicles formed by EIM and TFHM. The percent drug entrapment efficiency was found to be highest for formulations MTEIM-8 and MTTFHM-8 with values 97.11% and 95.56% respectively. In vitro dissolution studies were carried out in phosphate buffer (pH 6.8) for 8 hours at 100 rpm and maintained at 37 ± 0.5°C according to USP-II paddle method and absorbance was taken at 226 nm. The probable drug release mechanism may be fickian (class I) diffusion as the correlation coefficient (𝑅2) best fitted with zero order and release exponent (n) was less than 0.43.  The FTIR studies have been done to confirm no interaction along with drug and polymer. In vitro and ex vivo comparative studies showed that non-ionic surfactant vesicle had controlled the release of drug for a longer period. Finally, it can be concluded that non-ionic surfactant vesicle could be an effective for delivery of MT with increased bioavailability.

Author(s) Details

Dr. Irin Dewan
Pharmaceutical Technology Research Laboratory, Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Farmgate, Dhaka – 1215, Bangladesh.

Prof. Dr. S. M. Ashraful Islam
Pharmaceutical Technology Research Laboratory, Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Farmgate, Dhaka – 1215, Bangladesh.

Prof. Dr. Swarnali Islam Khandaker
Pharmaceutical Technology Research Laboratory, Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Farmgate, Dhaka – 1215, Bangladesh.

Waheeda Nasreen
Pharmaceutical Technology Research Laboratory, Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Farmgate, Dhaka – 1215, Bangladesh.

Ohinul Hoque
Pharmaceutical Technology Research Laboratory, Department of Pharmacy, University of Asia Pacific, 74/A, Green Road, Farmgate, Dhaka – 1215, Bangladesh.

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The Future of Prodrugs Design | Chapter 03 | Modern Advances in Pharmaceutical Research Vol. 2

When knowledge fails to provide answers to important questions such as how to improve the bioavailability of vital medications, “Imagination is more important than knowledge,” as Albert Einstein once said. Ingenuity in the design of effective prodrugs has been lacking in quantity and quality. The reasons behind the low quality of ingenuity could be related to the fact that medicinal chemists have expertise in organic and organometalic chemistry not in biochemistry and biology. On the other hand, pharmaceutical chemists, biologists and biochemists do not have the expertise to make sophisticated chemical devices. Therefore, in order for a prodrug strategy to work, a team consisting of all this expertise is necessary.

Author(s) Details

Professor Rafik Karaman
Department of Bioorganic Chemistry, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine and
Department of Sciences, University of Basilicata, Viadell’Ateneo Lucano 10, 85100, Potenza, Italy.

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