Biochemistry of Drug Resistance

Foreword
Preface
Contents
1 Introduction to Drugs, Drug Targets and Drug Resistance
1.1 Drugs
1.1.1 Classification of Drugs
1.2 Receptors (Drug Targets)
1.2.1 Types of Receptors
1.3 Drug Resistance
1.3.1 Mechanisms of Drug Resistance
1.3.2 Multidrug Resistance
1.3.3 Drug Resistance in Tumor
1.3.4 Economic Impact of Drug Resistance
References
2 Drugs Resistance in Bacterial Diseases
2.1 Introduction
2.2 Prevention and Control
2.3 Recent Developments in the Prevention of Antibiotic Resistance
2.4 Antibiotic Discovery and Supremacy
2.5 Causes of Antibiotic Resistance
2.6 Common Antibiotics Used Against Bacteria
2.6.1 Aminoglycosides
2.6.2 Amphenicols
2.6.3 Antifolates
2.6.4 β-lactams
2.6.5 Glycopeptides
2.6.6 Rifamycins
2.6.7 Macrolides
2.6.8 Quinolones
2.6.9 Tetracyclines
2.7 Conclusion
References
3 Drugs Resistance Against Viral Diseases
3.1 Introduction
3.2 Types of Viral Infections
3.3 History
3.4 Clinical Diagnostics
3.5 Pathogenesis
3.6 Management
3.6.1 Therapy and Chemoprophylaxis
3.6.2 Immunization
3.7 Viral Drug Therapy (Principles and Their Kinetics)
3.7.1 Viral Proteins
3.7.2 RNA Interference
3.7.3 Viral Mutagens
3.7.4 Cell Targets
3.7.5 Interferons
3.7.6 Maturation Inhibitors
3.8 Drug Resistance as Adaptive Process in Viral Infections (Possible Factors)
3.9 Evolution and Mechanism of Drug Resistance in Viral Infected Patients
3.9.1 Mutation in Virus Physiology and Biology
3.9.2 Adherence and Non-adherence of Antiviral Agent
3.9.3 Life Cycle Synchronization
3.10 Effect of Drug Resistance on Viral Replication and Pathogenesis
3.10.1 Molecular Mechanisms of Mutation Rates
3.11 Pharmacological Model for Viral Dynamics in Antiviral Treated Patients
3.11.1 Derivation of Models
3.12 Antiviral Drug Resistance Testing (In-Vitro Evaluation) in Viral Infected Patients
3.12.1 Principal of Drug Resistance Testing
3.13 Strategies for Improvement in Antiviral Agents Efficiency
3.14 Future of Antiviral Drug Resistance
3.15 Conclusion
References
4 Drug Resistance in Protozoal Infections
4.1 Introduction
4.2 Malaria
4.2.1 Drugs Related to Malaria (Mode of Action and Mechanism of Resistance)
4.2.2 Resistance to Chloroquine
4.2.3 Resistance to Primaquine
4.2.4 Resistance to Arylamino Alcohols
4.2.5 Resistance to Antifolate Drugs
4.2.6 Resistance to Artemisinin-Based Combination Therapy (ACT)
4.3 Toxoplasmosis
4.3.1 Drugs Related to Toxoplasmosis (Mode of Action and Mechanism of Resistance)
4.3.2 Resistance to Pyrimethamine
4.3.3 Resistance to Atovaquone
4.4 Babesiosis
4.4.1 Drugs Related to Babesiosis (Mode of Action and Mechanism of Resistance)
4.4.2 Resistance to Diminazene Aceturate
4.4.3 Resistance to Atovaquone
4.5 Cystoisosporiasis
4.5.1 Drugs Related to Cystoisosporiasis (Mode of Action and Mechanism of Resistance)
4.5.2 Resistance to Trimethoprim-Sulfamethoxazole
4.6 Trypanosomiasis
4.6.1 Drugs Related to Trypanosomiasis (Mode of Action and Mechanism of Resistance)
4.6.2 Resistance to Pentamidine
4.6.3 Resistance to Suramin
4.6.4 Resistance to Melarsoprol
4.7 Leishmaniasis
4.7.1 Drugs Related to Leishmaniasis (Mode of Action and Mechanism of Resistance)
4.7.2 Resistance to Sodium Stibogluconate
4.7.3 Resistance to Pentamidine
4.7.4 Resistance to Paromomycin
4.8 Giardiasis
4.8.1 Drugs Related to Giardiasis (Mode of Action and Mechanism of Resistance)
4.8.2 Resistance to Metronidazole
4.8.3 Resistance to Albendazole
4.9 Conclusion
References
5 Antifungal Drugs: Mechanism of Action and Resistance
5.1 Introduction
5.2 Problems with Comparing Antifungal and Antibacterial Resistance
5.3 Assessing Resistance Factors
5.4 Common Drugs Used Against Fungal Infections
5.4.1 Allylamines
5.4.2 Azoles
5.4.3 Echinocandin
5.4.4 Flucytosine
5.4.5 Polyenes
5.5 Conclusion
References
6 Drug Resistance in Ear, Nose, and Throat Infections
6.1 Introduction
6.2 Ear Infection
6.2.1 Otitis Media (Middle Ear Infection)
6.2.2 Swimmer’s Ear (Outer Ear Infection)
6.2.3 Otomycosis (Outer Ear Infection)
6.3 Nose Infection
6.3.1 Acute Rhinosinusitis
6.3.2 Chronic Rhinosinusitis
6.3.3 Allergic Rhinitis
6.4 Throat Infection
6.4.1 Colds and Flu
6.4.2 Pharyngitis
6.5 Conclusion
References
7 Drug Resistance in Skin Diseases
7.1 Introduction
7.2 Acne Vulgaris
7.2.1 Propionibacterium Acnes/Cutibacterium Acnes
7.2.2 Treatment Modalities of Acne
7.2.3 Antibiotic Resistance in Acne Vulgaris
7.2.4 Mechanism of Resistance to Tetracycline
7.3 Drug Resistance in Staphylococcus aureus
7.3.1 Mechanism of Action of Methicillin
7.3.2 Mechanism of Methicillin Resistance in S. aureus
7.3.3 Active Efflux System and Organization of Bacterial Cell Wall
7.3.4 Resistance to the β-Lactam Drugs
7.3.5 Resistance of S. aureus to Vancomycin
7.4 Skin Cancer
7.4.1 Melanoma Skin Cancer Treatment
7.4.2 Mechanism of Resistance to Chemotherapy in Melanoma
7.4.3 Resistance to Immunotherapy and Targeted Drug Therapy in Melanoma
7.4.4 Basal Cell Carcinoma
7.5 Herpes Simplex Virus (HSV)
7.5.1 Treatment Modalities of HSV
7.5.2 Acyclovir—A Nucleoside Analog
7.5.3 Mechanism of Viral Resistance
7.6 Leprosy
7.6.1 Treatment Modalities
7.6.2 Mechanism of Action of Dapsone
7.6.3 Drug Resistance in M. leprae
7.6.4 Mechanism of Resistance
7.7 Conclusion
References
8 Drugs Resistance in Lungs Diseases
8.1 Asthma
8.2 Severe Asthma in Children
8.2.1 Systemic Corticosteroids
8.2.2 Intramuscular Triamcinolone
8.2.3 Omalizumab
8.2.4 Mepolizumab
8.2.5 Dupilumab
8.3 Cystic Fibrosis/Bronchiectasis
8.3.1 Aminoglycosides
8.3.2 Fluoroquinolones
8.3.3 Beta-Lactams
8.3.4 Colistin
8.3.5 Other Antibiotics
8.4 Bronchitis
8.5 COPD (Chronic Obstructive Pulmonary Disease)
8.6 Chronic Cough
8.7 Blocked Lung Artery (Pulmonary Embolus)
8.8 Pulmonary Edema
8.8.1 Vasodilators
8.8.2 Morphine and Opiates
8.8.3 Angiogensin Converting Enzyme Inhibitors
8.8.4 Natriuretic Peptides
8.8.5 Inotropic and Inodilator Drugs
8.9 Treatment of Arrhythmias and/or Atrioventricular Resynchronization
8.10 Tuberculosis
8.11 Varied Lung Diseases
8.11.1 COVID-19—Coronavirus
8.11.2 Atelectasis
8.12 Lung Cancer
8.13 Sarcoidosis
8.14 Pleural Effusion
8.15 Conclusion
References
9 Neurological Disorders: Biochemistry of Drug Resistance and Future Challenges
9.1 Introduction
9.2 Huntington’s Disease
9.2.1 Treatment of Huntington Diseases and Drug Resistance
9.2.2 Tominersen (IONIS-HTTRx)
9.3 Parkinson Disease (PD)
9.3.1 Mechanisms of Disease and Genetics
9.3.2 Resistance Mechanism of PD Drugs
9.3.3 Monoamine Oxidase B (MAO-B) Inhibitors and Catechol-O-Methyl Transferase (COMT) Inhibitors
9.4 Epilepsy
9.4.1 Molecular Mechanisms of Epilepsy Drug Resistance Through Ion Channels, Transporters, Receptors and Metabolic Enzymes
9.5 Schizophrenia
9.5.1 Treatment of Schizophrenia
9.6 Conclusion
References
10 Drug Resistance in Kidney Diseases
10.1 Introduction
10.2 Genetic Basis of Kidney Disorders
10.3 Antiviral Drugs and Kidney Disease
10.4 Bacterial Resistance in Kidney Diseases
10.5 Drugs Resistance in Kidney Cancer
10.6 Anti-cytomegalovirus (CMV) Drug Resistance
10.7 Drug Resistance Prevention
10.8 Conclusion
References
11 Drugs Resistance in Heart Diseases
11.1 Introduction
11.2 Types of Heart Diseases
11.2.1 Congenital Heart Disease
11.2.2 Drugs Used in Congenital Heart Diseases
11.2.3 Dilated Cardiomyopathy
11.2.4 Coronary Artery Disease (CAD)
11.2.5 Cardiac Arrhythmia
11.2.6 Myocardial Infarction
11.2.7 Hypertension
References
12 Drug Resistance in Liver Diseases
12.1 Introduction
12.2 Hepatocellular Carcinoma
12.2.1 Multidrug Resistance Phenotype
12.2.2 ATP Binding Cassette (ABC) Transporters and Drug Resistance
12.2.3 Mechanism of Doxorubicin Antitumor Effects
12.2.4 Molecular Mechanisms of Doxorubicin Resistance
12.2.5 Resistance Mechanism of Etoposide
12.3 Hepatitis B
12.3.1 Molecular Mechanisms of Resistance Against (Nucleic Acids) NAs
12.4 Drug Resistance in Infectious Liver Cirrhosis
12.4.1 What is Liver Cirrhosis?
12.4.2 Antibiotics Resistance in Liver Cirrhosis
12.4.3 Quinolones
12.5 Pyogenic Liver Abscess
12.5.1 Bacteriology
12.5.2 K. Pneumoniae Genotype K1: An Emerging Pathogen that Causes Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess
12.5.3 Metronidazole Medicate Utilized for Treatment of Liver Abscess Disease
12.6 Conclusions
References
13 Drug Resistance in Cancer
13.1 Introduction
13.1.1 Drug Resistance in Cancer
13.1.2 High Level of Drug Efflux
13.1.3 Lower Level of Drug Efflux
13.1.4 Mutations in Tumor Cells (Epigenetic Alteration)
13.1.5 Non-coding RNA Involvement
13.1.6 Exosome Derived miRNA Involvement
13.1.7 Apoptotic Arrest
13.1.8 Drug Inactivation
13.1.9 Multiple Drug Resistance
13.2 Mechanisms of Cancer Drug Resistance
13.2.1 Ovarian Cancer Drug Resistance
13.2.2 Prostate Cancer Drug Resistance
13.2.3 Breast Cancer Drug Resistance
13.2.4 Colon Cancer Drug Resistance
13.2.5 Lung Cancer Drug Resistance
13.3 How to Combat Cancer Drug Resistance?
13.3.1 Targeted Autophagy
13.3.2 Co-delivery of siRNA and Chemotherapeutic Drugs
13.3.3 Combinational Drug Therapy
13.3.4 Therapeutic Drugs Usage
13.3.5 Use of Natural Compounds
13.4 Proteomic and Genomic Analysis of Cancer Drug Resistance
13.5 Future Recommendations
References
14 Drugs Resistance and Treatment Failure in HIV and/or AIDS
14.1 Introduction
14.2 Current Medication and Related Mutations
14.3 Mechanism of HIV Drug Resistance
14.4 Drug Resistance Testing
14.5 Next Generation Medicine in HIV
14.6 Broadly Neutralizing Antibodies
14.7 Therapeutic HIV Vaccines
14.8 Future Directions for Developing Daily HIV Drugs
14.8.1 Future Perspective
14.9 Conclusion
References
15 Drug Resistance in Reproductive Diseases
15.1 Introduction
15.2 Infections in Reproductive System
15.2.1 Bacterial Infections
15.2.2 Viral Infections
15.2.3 Fungal Infections
15.3 General Mechanism of Drug Resistance in Reproductive Diseases
15.4 Drug Resistance in Reproductive System
15.4.1 Bacterial Drug Resistance
15.4.2 Viral Drug Resistance
15.4.3 Fungal Drug Resistance
15.5 Conclusion
References
16 Drug Resistance in Diabetes
16.1 Introduction
16.1.1 Types of Diabetes
16.1.2 Type-1 Diabetes
16.1.3 Type-2 Diabetes
16.1.4 Gestational Diabetes Mellitus
16.2 Pathophysiology of Type-1 Diabetes
16.3 Pathophysiology of Type-2 Diabetes
16.4 Anti-diabetic Medication-Oral and Insulin
16.5 Factors Affecting the Body’s Response to Drugs
16.6 Interactions Between Drug-Food and Drug-Drug
16.7 Interactions Between Drug, Expectations, and Personal Behavior
16.8 Oxidative Stress: The Pathogenic Mechanism Underlying Insulin Resistance
16.9 Drug Resistance in Diabetes
16.10 Prevention and Treatment of Drug Resistance
16.11 Precautionary Measures and Management of Drug Resistant
16.12 Future Perspectives of Diabetes Treatment and Drug Resistance
16.13 Future Treatment Solutions for Diabetes
16.14 Association Between Diabetes Mellitus, Other Diseases and Their Drug Therapies
16.15 Conclusion
References
17 Drug Resistance in Rheumatological Diseases
17.1 Introduction
17.2 Mechanism of Action of Antirheumatic Drugs
17.3 Conventional DMARDs
17.3.1 Methotrexate
17.3.2 Leflunomide
17.3.3 Sulfasalazine
17.3.4 Hydroxychloroquine
17.3.5 Cyclophosphamide
17.4 Biological DMARDs
17.4.1 Anti-TNF Alpha Monoclonal Antibodies
17.4.2 Etanercept
17.4.3 Abatacept
17.4.4 Rituximab
17.4.5 Tocilizumab
17.4.6 Anakinra
17.4.7 Janus Kinase (JAK) Inhibitors
17.5 Mechanism of Resistance Against Anti-rheumatic Drugs
17.5.1 Efflux Pumps
17.5.2 P-glycoprotein (P-gp)
17.5.3 Breast Cancer Resistance Protein (BCRP)
17.5.4 Multidrug Resistance Associated Protein 1 (MRP1)
17.5.5 Organic Anion Transporter 3 (OAT3)
17.5.6 Antidrug Antibodies
17.5.7 Alternative Inflammatory Mediators
17.5.8 Genetic Polymorphisms
17.5.9 Down-Regulation of Receptors/reprogramming of Stimulatory Signals
17.6 Strategies Adopted to Overcome Resistance and Future Prospects
17.6.1 Reduction/Suppression/Bypass of Transmembrane Carriers
17.6.2 Modifying Signal Transduction
17.6.3 Combination with Other Agents
17.6.4 Alternative Drugs with Similar End-Targets
17.7 Conclusion
References
18 Pherotypes in Streptococcus Pneumoniae and Role of CSP-1 and CSP-2 in Antibiotic Susceptibility and Resistance; Towards Development of Live Attenuated Vaccine Candidates in Inducing Netosis Based Acquired Immune Response
18.1 Introduction
18.2 Detection Mechanisms of the Pherotype and Endonuclease Restriction Phenotype by PCR Method
18.3 Different Methods to Identify Susceptibility and Resistance
18.3.1 Kirby Bauer Method
18.3.2 E Test
18.3.3 Agar Dilution Test
18.4 Quorum Sensing and Immunity
18.5 Current S. pneumoniae Vaccine
18.6 NETosis and Immunity
18.7 Conclusion
References
19 Hypoxia, Obesity and Drug Resistance; Towards Sustainable Development Goals and Globalization
19.1 Introduction
19.2 Effective Mechanism of Role of Hypoxia
19.3 Obesity and Nutrigenetics
19.4 Conclusion
References
20 Genetic and Molecular Mechanisms of Multidrug-Resistance in Uropathogens and Novel Therapeutic Combat
20.1 Urinary Tract Infections
20.2 Types
20.2.1 Pyelonephritis
20.2.2 Cystitis
20.2.3 Urethritis
20.3 Pathogenesis
20.3.1 Portal Of Uropathogens Entry
20.3.2 Mechanism of Urinary Tract Infections (UTIs)
20.4 Uropathogens
20.4.1 Gram-Negative Bacteria
20.4.2 Gram-Positive Bacteria
20.5 Pathogenicity Causing Element
20.5.1 Toxins and Proteases Enzymes
20.5.2 Ureases Enzymes
20.5.3 Uptake of Iron
20.6 Antibiotics and Their Mechanism
20.6.1 Multidrug Resistance Uropathogens
20.6.2 Combination Therapies
20.6.3 Anti-virulence Therapy by Targeting Bacterial Adhesion
20.6.4 Anti-virulence Therapy by Targeting Bacterial Toxins and Proteases
20.6.5 Anti-virulence Therapy by Targeting Bacterial Siderophores
20.6.6 Small Molecules Targeting Urease
20.6.7 Small Molecules Targeting Bacterial Adhesion
20.6.8 Nanoparticle-Based Therapy
20.7 Conclusion
References
21 Drugs Resistance Management
21.1 What is Drug Resistance?
21.2 How Drug Resistance Develops?
21.3 Types of Antibiotics Resistances
21.4 Drug Resistance Sources
21.4.1 Drug Use in Humans
21.5 Environment
21.6 Fungal Cell Wall and Drug Resistance
21.7 Echinocandin
21.8 Need of Drug Resistance Management
21.9 Methods to Combat Drug Resistance
21.10 Clinical Management
21.11 Vaccines or Immunization
21.12 Developing Generation of Antibiotics
21.13 Stable Zone Strategy
21.14 Treatment Cycling
21.15 Altering Doses of Drugs or Combinations
21.16 Health Education
21.17 Stopping Spread of Antibiotic Resistance
21.18 Environmental and Sanitization Management in Combating Resistance
References