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