Pharmacological Treatment of Alzheimer's Disease: Scientific and Clinical Aspects

Description

Alzheimer’s disease is the most prevalent form of dementia. Although it was discovered about a century ago, the first drugs applied in treatment were only introduced in therapy in the last 30 years. This book focuses on the clinical pharmacology of drugs that aim to delay the progression of Alzheimer’s disease, such as anticholinesterases and glutamate receptor antagonists, as well as treatment for the behavioral changes caused by the progression of the disease: antidepressants, antipsychotics, anxiolytics, and mood stabilizers. In addition, it describes important information about the pathophysiology and diagnostic methods of Alzheimer’s disease, emergency situations conditioned by the dementia process, and presents new perspectives for the treatment of Alzheimer’s disease. The ten chapters cover topics such as mechanism of action, dosage regimen, adverse reactions, drug interactions, toxicity profiles, among other information of clinical relevance. The work comprises evidence-based studies, providing a valuable resource for analyzing, prescribing and monitoring patients being treated for Alzheimer’s disease. Written by experts with solid professional experience, this book will appeal to pharmacologists, geriatricians, neurologists, psychiatrists, biomedical clinicians, and other healthcare professionals. Preface Acknowledgments Contents Contributors Chapter 1: Introduction 1.1 The Origin of the Alzheimer’s Disease and Advances in Pharmacology 1.1.1 Pharmacological Treatment: Therapy Through the Use of Medications 1.1.2 Advances in the Treatment of Alzheimer’s Disease References Chapter 2: Principles of Pharmacology in Dementia 2.1 Introduction 2.1.1 Pathophysiology 2.1.1.1 The Cholinergic Hypothesis 2.1.1.2 The Amyloid Cascade Hypothesis 2.1.2 Diagnosis 2.1.3 Treatment 2.1.4 Lewy Body Dementia and Dementia in Parkinson’s Disease 2.1.5 Frontotemporal Dementia 2.1.6 Vascular Dementia 2.1.7 Alzheimer’s Disease 2.2 Non-pharmacological Treatment 2.2.1 Therapies for Improved Cognitive Functioning References Chapter 3: The Viability of Treatment Conditioned to the Pathophysiology of Alzheimer’s Disease 3.1 Cholinergic Hypothesis 3.1.1 The Cholinergic Hypothesis and the Metabolism of Acetylcholine 3.1.2 Pharmacological Implications of the Cholinergic Hypothesis 3.1.3 Impact of Cerebrovascular Risk Factors on Cholinergic Activity 3.1.4 Interactions of Cholinergic Pathways with Other Neurotransmitter Systems in the Brain 3.1.5 The Cholinergic Hypothesis and the Amyloid Cascade 3.2 Tau Protein and Amyloid-β 3.2.1 Metabolism of Amyloid-β 3.2.2 Proteolysis of the Amyloid Precursor Protein 3.2.3 Pathogenesis of Amyloid-β Plaques 3.2.4 Degradation and Clearance of Amyloid-β 3.2.5 Metabolism of Tau 3.2.6 Clinical-Biomarker Correlations 3.2.7 Interactions of Cerebrovascular Metabolism with Amyloid-β and Tau Pathology 3.2.8 Interactions of Hormonal and Inflammatory Mechanisms with Amyloid-β and Tau Pathology 3.2.9 Interactions of Amyloid-β and Tau Pathology with Excitotoxic Mechanisms 3.2.10 Future Prospects References Chapter 4: The Use of Esterase Inhibitors 4.1 Galantamine 4.1.1 A Big Picture of Galantamine 4.1.2 Protocols with Galantamine 4.1.3 Drug Interactions Involving Galantamine 4.2 Donepezil 4.2.1 A Big Picture of Donepezil 4.2.2 Protocols with Donepezil 4.2.3 Drug Interactions Involving Donepezil 4.3 The Failure of Tacrine 4.4 Rivastigmine 4.4.1 Pharmacology of Rivastigmine 4.4.2 Clinical Trials 4.4.3 Carbamate 4.4.4 Pharmacokinetics 4.4.5 Adverse Events 4.4.6 Drug Interactions 4.4.7 Doses and Administration 4.4.8 Transdermal Use of Rivastigmine 4.4.9 Storage References Chapter 5: Pharmacology of NMDA (N-Methyl-D-Aspartate) Receptor Antagonists in Alzheimer’s Disease 5.1 Glutamate and Its Receptors 5.2 NMDA (N-Methyl-D-Aspartate) Receptors and Alzheimer’s Disease 5.3 Pharmacology of NMDAr and Alzheimer 5.3.1 The Big Picture and Beginning of the Clinical Use 5.3.2 NMDAR Pharmacology 5.4 Memantine 5.4.1 Big Picture of Memantine 5.4.2 Dose and Administration of Memantine 5.4.2.1 Memantine as a Single Agent (Table 5.1) 5.4.2.2 Combination Therapy with Memantine 5.5 Drug Interactions Involving Memantine and Clinical Conditions That Can Alter Its Pharmacology 5.5.1 Raised Urinary pH 5.5.1.1 Raised Urinary pH by Diet 5.5.1.2 Renal Conditions: Renal Tubular Acidosis and Severe Infections of the Urinary Tract 5.5.1.3 Carbonic Anhydrase Inhibitors 5.5.1.4 Sodium Bicarbonate 5.5.1.5 Drugs Eliminated via Renal Mechanism References Chapter 6: Supportive Pharmacological Treatment 6.1 Antidepressants 6.2 Antipsychotics 6.2.1 Typical 6.2.2 Atypical 6.3 Anxiolytics 6.4 Mood Stabilizers 6.5 Vitamins 6.6 Antioxidants 6.7 Secondary Treatment References Chapter 7: Herbal Medicines and Supplements 7.1 Introduction 7.2 Traditional Proposals of Indian Medicine 7.3 Proposals of Traditional Chinese Medicine 7.4 Proposals of Western Phytotherapy 7.4.1 Acetylcholine 7.4.2 Gamma-Aminobutyric Acid (GABA) 7.4.3 Glutamate 7.4.4 Phytocompounds Absorbed by Western Pharm Therapy 7.4.5 Adaptogenic Phytotherapies and New Ways 7.4.5.1 Neurotrophins: A New Way 7.5 The Alliance of Phytotherapy with Nanotechnology 7.5.1 Lipid Nanoparticles (NLs) 7.5.2 Transcytosis 7.5.3 Transport Mechanisms Through BBB 7.5.4 Pharmacological Carriers for the Central Nervous System: Lipid Nanoparticles 7.5.5 Nanoparticles (NPs) 7.6 Neurodegenerative Diseases References Chapter 8: Emergency Situations 8.1 Acute Mental Changes in Alzheimer’s Disease 8.1.1 Delirium in Alzheimer’s Disease 8.1.2 Epileptic Seizures in Patients with Alzheimer’s Disease 8.1.3 Behavioral and Psychological Symptoms of Dementia 8.1.4 Drug Reactions 8.2 Acute Motor Deficits in Alzheimer’s Disease 8.2.1 Stroke and Stroke Mimics in Alzheimer’s Disease 8.2.2 Acute Subdural Hematoma and Other Acute Traumatic Brain Injury in Alzheimer’s Disease 8.3 Conclusion References Chapter 9: Relationships Between Treatment and Clinical Evaluations 9.1 The Laboratory Tests 9.1.1 Aspects of Treatment and Relationship with Laboratory Tests and Clinical Evolution of Alzheimer’s Disease 9.1.2 Clinical-Laboratory Aspects 9.2 Image 9.3 Magnetic Resonance Imaging 9.4 Computed Tomography 9.5 Behavior Assessments References Chapter 10: New Perspectives for Treatment in Alzheimer’s Disease 10.1 Introduction 10.2 Oxidative Stress 10.2.1 Oxidative Stress 10.2.2 Chelators 10.2.2.1 Clioquinol (5-Chloro-7-Iodo-Quinolin-8-Ol) and PBT2 (a 8-Hydroxyquinoline Analog) 10.2.2.2 Bis-8-Aminoquinoline Derivatives (PA1637) 10.2.3 Metamorphosizers 10.2.4 Receptors for Advanced Glycation End Products (RAGE) 10.3 Active and Passive Immunotherapy 10.3.1 Vaccines 10.3.1.1 ABvac40 10.3.1.2 GV1001 10.3.1.3 AADvac1 10.3.2 Amyloid-Based Passive Immunotherapy 10.3.2.1 Bapineuzumab (AAB-001) 10.3.2.2 Solanezumab (LY2062430) 10.3.2.3 Gantenerumab (RO4909832) 10.3.2.4 Crenezumab (MABT5102A) 10.3.2.5 Aducanumab (BIIB037) 10.3.2.6 Donanemab (LY3002813) 10.4 Enzyme Inhibitors 10.4.1 BACE Inhibitors 10.4.1.1 Atabecestat (JNJ-54861911) 10.4.1.2 Verubecestat (MK8931) 10.4.1.3 Lanabecestat (AZD3293) 10.4.1.4 Umibecestat (CNP520) 10.4.1.5 Elenbecestat (E2609) 10.5 Other Perspectives 10.5.1 Tau-Based Therapies 10.5.2 Lithium 10.5.3 Other Mechanisms of Action 10.6 Conclusion References Index