Introduction to Basics of Pharmacology and Toxicology: Volume 2: Essentials of Systemic Pharmacology: From Principles to Practice

Description

This book explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences. Foreword Preface Preface to Volume 1: General and Molecular Pharmacology: Principles of Drug Action (https://link.springer.com/book/10.1007/978... Acknowledgments Contents Editors and Contributors Part I: Autonomic Nervous System 1: Cholinoceptor Agonists and Anticholinesterase Agents 1.1 Introduction 1.2 Synthesis and Degradation of ACh 1.3 Cholinergic Receptors 1.4 Action of ACh in Different Organ Systems 1.4.1 Central Nervous System 1.4.2 Heart 1.4.3 Blood Vessels 1.4.4 Lungs 1.4.5 Gastrointestinal Tract 1.4.6 Urinary Tract 1.4.7 Eye 1.4.8 Glands 1.4.9 Skeletal Muscles 1.4.10 Ganglion 1.5 Cholinomimetic Drugs 1.5.1 Classification 1.5.2 Direct Muscarinic Agonists 1.5.3 Toxicology of Muscarinic Alkaloids 1.5.4 AChE and Anticholinesterases 1.5.5 Pharmacological Actions of Anticholinesterases 1.5.6 Therapeutic Uses of Anticholinesterases 1.6 Toxicology of Anticholinesterases: Management of OPC and Carbamate Poisoning 1.6.1 Acute Organophosphorus Poisoning 1.6.2 Acute Carbamate Poisoning 1.6.3 Intermediate Syndrome in OPC Poisoning 1.6.4 Delayed Neuropathy in OPC Poisoning Bibliography 2: Cholinoceptor Antagonists 2.1 Introduction 2.2 Classification 2.3 Chemistry and Structure-Activity Relationship 2.4 Pharmacological Actions 2.4.1 Central Nervous System 2.4.2 Heart 2.4.3 Blood Vessels and Blood Pressure 2.4.4 Respiratory System 2.4.5 Eye 2.4.6 Gastrointestinal Tract 2.4.7 Urinary Bladder 2.4.8 Glands 2.4.9 Body Temperature 2.5 Individual Drugs 2.6 Therapeutic Uses 2.6.1 As Mydriatic and Cycloplegic 2.6.2 As Spasmolytics 2.6.3 Management of Overactive Bladder 2.6.4 As Pre-Anesthetic Medication 2.6.5 Bronchial Asthma and COPD 2.6.6 Motion Sickness 2.6.7 Arrhythmias 2.6.8 Drug-Induced Parkinsonism 2.6.9 In Poisoning 2.6.10 Other Uses with Unproven Efficacy 2.7 Adverse Effects and Contraindications 2.8 Management of Anticholinergic Poisoning 2.9 Ganglion Blockers Bibliography 3: Adrenergic Agonists 3.1 Organ Specific Effects of Adrenergic Agonists 3.1.1 Cardiovascular System 3.1.1.1 Effect of the Alpha 1 Receptor Activation Vascular Tone Cardiac Parameters Blood Pressure 3.1.1.2 Effect of Alpha 2 Receptor Activation Peripheral Action Central Action 3.1.1.3 Effect of Beta 1 Receptor Activation Cardiac Parameters 3.1.1.4 Effect of Beta 2 Receptor Activation 3.1.1.5 Effect of Dopamine Receptor Activation 3.1.2 Effects on Other Organ Systems (Box 3.1) Box 3.1 Effects on Other Organ Systems 3.2 Sympathomimetic Drugs 3.2.1 Endogenous Catecholamines 3.2.1.1 Epinephrine Pharmacokinetics Mechanisms of Action on Various Organ Systems and Uses of Epinephrine Adverse Drug Reactions Uses of Epinephrine 3.2.1.2 Norepinephrine Cardiovascular System Adverse Drug Reactions Therapeutic Uses 3.2.1.3 Dopamine Pharmacokinetics Adverse Drug Reactions Therapeutic Uses Drugs Similar to Dopamine 3.2.2 Non-selective Beta Agonists 3.2.2.1 Isoproterenol Therapeutic Uses Adverse Drug Reactions 3.2.2.2 Dobutamine Pharmacokinetics Therapeutic Uses Adverse Drug Reactions 3.2.3 Beta 2 Selective Receptor Agonists 3.2.3.1 Adverse Drug Reactions Box 3.2 Drugs Used in the Pharmacotherapy of Asthma and COPD 3.2.3.2 Terbutaline 3.2.3.3 Ritodrine 3.2.4 Beta 3 Receptor Agonists 3.2.4.1 Mirabegron 3.2.5 Alpha 1 Agonists 3.2.5.1 Phenylephrine 3.2.5.2 Midodrine 3.2.6 Alpha 2 Agonists 3.2.6.1 Clonidine Box 3.3 Miscellaneous Alpha 2 Agonists 3.2.7 Indirect Sympathomimetic Drugs 3.2.7.1 Amphetamine Box 3.4 Amphetamine-Like Drugs 3.2.7.2 Cocaine 3.2.8 Mixed Acting Agents 3.2.8.1 Ephedrine 3.2.8.2 Metaraminol Bibliography 4: Adrenergic Antagonists 4.1 Alpha Blockers 4.1.1 Effects of Alpha Receptor Blockade 4.1.1.1 Effects of Alpha 1 Blockade 4.1.1.2 Effects of Alpha 2 Blockade 4.1.2 Nonselective Alpha Antagonists 4.1.2.1 Treatment of Pheochromocytoma 4.1.2.2 Other Clinical Uses (Phentolamine) 4.1.2.3 Adverse Drug Reactions 4.2 Alpha 1 Selective Receptor Antagonists 4.2.1 Prazosin 4.2.1.1 Clinical Effects of Prazosin 4.2.1.2 Adverse Drug Reaction 4.2.1.3 Uses of Prazosin 4.2.2 Terazosin 4.2.3 Doxazosin 4.2.4 Tamsulosin 4.2.5 Silodosin 4.3 Alpha 2 Receptor Antagonists 4.3.1 Yohimbine 4.4 Beta Blockers 4.4.1 Effect on the Cardiovascular System 4.4.1.1 Heart 4.4.1.2 Conducting Tissue 4.4.1.3 Vasculature 4.4.2 Pulmonary System 4.4.3 Metabolic Effects 4.4.4 Special Properties of Various Beta Blockers 4.4.4.1 Nonselective Beta Blockers (First Generation) 4.4.4.2 Beta 1 Selective Blockers (Second Generation or Cardioselective Beta Blockers) 4.4.4.3 Beta Blockers with Additional Cardiovascular Effects (Third Generation Beta Blockers) (Box 4.1) Box 4.1: Third Generation Beta Blockers 4.4.5 Common Uses of Beta Blockers 4.4.6 Adverse Effects of Beta Blockers (Box 4.2) Box 4.2: Toxicity Profile of Beta Blockers Bibliography Part II: Central and Peripheral Nervous System 5: Neurotransmitters and Neurotransmission 5.1 Introduction 5.2 Relevant Anatomy 5.2.1 Cerebral Cortex 5.2.2 Diencephalon 5.2.3 Limbic System 5.2.4 Midbrain and Brainstem (Pons and Medulla) 5.2.5 Cerebellum 5.2.6 Spinal Cord 5.3 Neurochemical Transmission in the CNS 5.3.1 Neurotransmitters 5.3.2 Neuromodulators 5.3.3 Neuromediators (Second Messengers) 5.3.4 Neurohormones 5.3.5 Neurotrophic Factors 5.3.6 Co-transmission 5.4 Classification of Neurotransmitters 5.5 Receptors Involved in Neurotransmission 5.6 Amino Acids as Neurotransmitters 5.6.1 Gamma-Aminobutyric Acid (GABA) 5.6.2 Glycine 5.6.3 Glutamate 5.7 Amine Neurotransmitters 5.7.1 Acetylcholine 5.7.2 Dopamine 5.7.3 Norepinephrine 5.7.4 Epinephrine 5.7.5 Serotonin (5-hydroxytryptamine) 5.7.6 Histamine 5.8 Peptides as Neurotransmitters 5.9 Purines 5.10 Gaseous Neurotransmitters 5.10.1 Nitric Oxide 5.10.2 Carbon Monoxide 5.11 Lipid Mediators Bibliography 6: Hypnotics and Sedatives 6.1 Introduction 6.1.1 History 6.2 Benzodiazepines 6.2.1 Introduction Box 6.1: Classification of Benzodiazepines Based on Their Pharmacological Action 6.2.2 Mechanism of Action 6.2.2.1 Molecular Pharmacology of GABAA Receptor-Cl- Channel Complex Box 6.2: Pharmacological Actions Mediated by Different Benzodiazepines Based on Subtype Binding of α Subunit of GABAA Receptor... 6.2.3 Pharmacological Actions 6.2.3.1 CNS Effects 6.2.3.2 Systemic Effects 6.2.4 Pharmacokinetics Box 6.3: Routes of Administration of Benzodiazepines Box 6.4: Benzodiazepines Categorized Based on Their Elimination Half-Lives 6.2.5 Drug Interactions 6.2.6 Adverse Effects 6.2.7 Therapeutic Uses (Table 6.3) 6.3 Barbiturates 6.3.1 Introduction 6.3.2 Mechanism of Action 6.3.3 Pharmacological Actions 6.3.4 Pharmacokinetics Box 6.5: Routes of Administration of Various Barbiturates 6.3.5 Adverse Effects 6.3.6 Contraindications 6.3.7 Drug Interactions 6.3.8 Acute Barbiturate Poisoning 6.3.9 Therapeutic Uses 6.4 Non-Benzodiazepines or Non-Benzodiazepine Receptor Agonists (Non-BzRAs) 6.5 Benzodiazepine Antagonist: Flumazenil 6.5.1 Mechanism of Action 6.5.2 Pharmacokinetics 6.5.3 Adverse Effects 6.5.4 Uses 6.6 Newer Sedative-Hypnotics Acting Through Other Mechanisms 6.6.1 Melatonin Receptor Agonists 6.6.1.1 Ramelteon 6.6.1.2 Tasimelteon 6.6.2 Orexin Receptor Antagonists (Sleep-Enabling Drugs) 6.6.2.1 Dual Orexin Receptor Antagonists (DORAs) 6.6.2.2 Suvorexant 6.6.3 Tricyclic Antidepressant: Doxepin 6.7 Management of Insomnia Box 6.6: Classification of Insomnia Box 6.7: Management of Insomnia 6.8 Sedative-Hypnotics in the Evolving Stage Box 6.8: Newer Drugs Under Trial for the Treatment of Insomnia 6.8.1 Molecular Targets for Newer Sedative-Hypnotics Bibliography 7: Pharmacotherapy of Seizures 7.1 Introduction 7.2 Pharmacokinetics of Anti-Seizure Medications 7.3 Drug Interactions of Anti-Seizure Medications 7.4 Mechanism of Action of Anti-Seizure Medications 7.5 Classification of Anti-Seizure Medications 7.5.1 Drugs Acting Primarily on GABA 7.5.1.1 Barbiturates: Phenobarbitone, Primidone 7.5.1.2 Benzodiazepines: Diazepam, Clonazepam, Lorazepam, Clobazam, Clorazepate 7.5.1.3 Valproate 7.5.1.4 Gabapentin and Pregabalin 7.5.1.5 Tiagabine 7.5.1.6 Vigabatrin 7.5.1.7 Stiripentol 7.5.1.8 Ganaxolone 7.5.2 Sodium Channel Modulators 7.5.2.1 Phenytoin 7.5.2.2 Carbamazepine 7.5.2.3 Oxcarbazepine 7.5.2.4 Lamotrigine 7.5.2.5 Felbamate 7.5.2.6 Topiramate 7.5.2.7 Lacosamide 7.5.2.8 Rufinamide 7.5.3 Calcium Channel Modulators 7.5.3.1 Ethosuximide 7.5.3.2 Zonisamide 7.5.4 Drugs with Novel Mechanisms of Action 7.5.4.1 Levetiracetam 7.5.4.2 Perampanel 7.5.4.3 Lamotrigine 7.5.4.4 Acetazolamide 7.5.4.5 Phenobarbitone and Topiramate 7.6 Newer Drugs in Development 7.6.1 Brivaracetam 7.6.2 Eslicarbazepine Acetate 7.6.3 Retigabine (Ezogabine) 7.6.4 Carisbamate 7.7 Clinical Management of Epilepsy 7.8 Status Epilepticus Bibliography 8: General Anesthetics 8.1 Evolution of Anesthetic Agents 8.2 Inhalational Anesthetic Agents 8.2.1 Classification: Based on Mechanism of Action 8.2.2 Pharmacokinetics of Inhalational Anesthetic Agents 8.2.2.1 General Considerations 8.2.2.2 Determinants of Partial Pressure Gradients 8.2.2.3 Solubility and Partition Coefficient 8.2.2.4 Tissue Blood Partition Coefficients 8.2.3 Pharmacodynamics of Inhaled Anesthetic Agents 8.2.3.1 Minimum Alveolar Concentration 8.2.3.2 Mechanism of Action of Inhalational Anesthetic Agents 8.2.4 Effect of Inhalational Anesthetic Agents on Organs 8.2.4.1 CNS 8.2.4.2 CVS 8.2.4.3 RS 8.2.4.4 Liver 8.2.4.5 Renal 8.2.4.6 Other Systems 8.2.5 Comparison of Inhalational Anesthetic Agents 8.3 Inducing (Parenteral) Anesthetic Agents 8.3.1 Introduction 8.3.2 Ideal Properties of Inducing Agents 8.3.3 Classification: Based on Mechanism of Action 8.3.4 Comparison of Inducing Agents Used in Anesthesia 8.4 Clinical Pharmacology of General Anesthetic Agents 8.4.1 Anesthesia in Liver Failure 8.4.2 Anesthesia in Renal Failure 8.4.3 Anesthesia in Seizure Disorders 8.4.4 Anesthesia in the Pediatric Population 8.4.5 Anesthesia in Pregnancy Bibliography 9: Drug Therapy of Psychosis and Mania 9.1 Pharmacotherapy of Psychosis 9.1.1 Typical Antipsychotics 9.1.2 Atypical Antipsychotics 9.2 Pharmacotherapy of Mania (Mood Stabilizers) 9.2.1 Lithium as Mood Stabilizer 9.2.2 Antiepileptics as Mood Stabilizers 9.2.3 Antipsychotics as Mood Stabilizers 9.2.4 Other Adjuvants for Bipolar Disorder Bibliography 10: Pharmacotherapy of Depression and Anxiety Disorders 10.1 Pharmacotherapy of Depression 10.1.1 Introduction 10.1.2 Drugs Used for Depression: Antidepressants 10.1.3 Common Mechanistic Pathways for Antidepressants 10.1.4 Classification of Antidepressants 10.1.4.1 Tricyclic Antidepressants (TCAs) 10.1.4.2 Selective Serotonin Reuptake Inhibitors (SSRIs) 10.1.4.3 Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) 10.1.4.4 Atypical Antidepressants 10.1.4.5 Monoamine Oxidase Inhibitors (MAOIs) 10.1.5 Clinical Uses of Antidepressants (Other than in Depressive Disorders) Box 10.1 Alternative Uses of Antidepressants 10.1.6 Advances in Antidepressant Therapy 10.2 Pharmacotherapy of Anxiety Disorders 10.2.1 Drugs for Treatment of Anxiety Disorders (Anti-Anxiety Drugs) 10.2.1.1 Antidepressants as Anti-Anxiety Drugs 10.2.1.2 Benzodiazepines Box 10.2 BZDs Used in Anti-Anxiety Therapy 10.2.1.3 Anticonvulsants 10.2.1.4 Beta Blockers 10.2.1.5 Azapirones 10.2.1.6 Sedative Antihistaminics 10.2.2 Advances in Anti-Anxiety Drugs Bibliography 11: Pharmacotherapy of Neurodegenerative Disorders 11.1 Parkinson´s Disease 11.1.1 Function of Basal Ganglia 11.1.2 Causes of PD 11.1.3 Symptoms of PD Include 11.1.4 Treatment of PD 11.1.4.1 Levodopa (L-DOPA, L-Dihydroxyphenylalanine) 11.1.4.2 Dopamine Receptor Agonists (Ropinirole and Pramipexole) 11.1.4.3 Catechol-O-Methyltransferase (COMT) Inhibitors 11.1.4.4 Selective MAO-B Inhibitors 11.1.4.5 Anti-cholinergic Agents 11.1.4.6 Newer Drugs 11.2 Alzheimer´s Disease (AD) 11.3 Amyotrophic Lateral Sclerosis (ALS) Bibliography 12: Opioid Agonists and Antagonists 12.1 Definitions 12.2 Endogenous Opioid Peptides 12.3 Opioid Receptors 12.4 Effects of Clinically Used Opioids (Table 12.1) 12.5 Classification of Opioids (Box 12.1 and 12.2) Box 12.1 Opioid classification based on synthetic process Box 12.2 Opioid classification based on chemical structure/activity 12.6 Opioid Agonists 12.6.1 Morphine and its Congeners 12.6.1.1 Morphine 12.6.1.2 Codeine 12.6.1.3 Heroin 12.6.1.4 Hydromorphone 12.6.1.5 Oxycodone 12.6.1.6 Hydrocodone 12.6.1.7 Oxymorphone 12.6.1.8 Levorphanol 12.6.2 Piperidine Analgesics 12.6.2.1 Meperidine 12.6.2.2 Diphenoxylate 12.6.2.3 Loperamide 12.6.3 Fentanyl and its Congeners (Phenylpiperidine Analgesics) 12.6.3.1 Fentanyl and Sufentanil 12.6.3.2 Remifentanil 12.6.4 Other Opioid Agonists 12.6.4.1 Methadone 12.6.4.2 Tramadol 12.6.4.3 Tapentadol 12.6.4.4 Dextromethorphan 12.6.4.5 Pholcodine and Benzonatate 12.7 Opioid Partial Agonists 12.7.1 Pentazocine 12.7.2 Nalbuphine 12.7.3 Butorphanol 12.7.4 Buprenorphine 12.8 Opioid Antagonists 12.8.1 Pharmacological Properties 12.8.2 Effects in the Absence of Opioid Agonist 12.8.3 Effects in the Presence of Opioid Agonists 12.8.4 Effects in Opioid Dependent Patients 12.8.5 ADME 12.8.6 Therapeutic Uses 12.8.6.1 Treatment of Opioid Overdoses 12.8.6.2 Managing Constipation 12.8.6.3 Management of Abuse Syndromes 12.9 Routes of Analgesic Drug Administration 12.9.1 Patient Controlled Analgesia 12.9.2 Spinal Delivery 12.9.3 Rectal Administration 12.9.4 Transmucosal (Oral) Administration 12.9.5 Transnasal Administration 12.9.6 Transdermal Administration 12.10 Guidelines for Opiate Dosing 12.11 Factors Affecting Opioid Variability 12.12 Nonanalgesic Uses of Opioids 12.12.1 Dyspnoea 12.12.2 Anaesthetic Adjuvants 12.13 Acute Opioid Toxicity 12.13.1 Symptoms and Diagnosis 12.13.2 Treatment Bibliography 13: Cognition Enhancers, Psychostimulants, and Psychedelic Drugs 13.1 Introduction Box 13.1 List of Drugs Which Act as Cognition Enhancers, Psychostimulants, and Psychedelics 13.2 Cognition Enhancers 13.2.1 Cholinergic Activators 13.2.1.1 Tacrine 13.2.1.2 Rivastigmine 13.2.1.3 Donepezil 13.2.1.4 Galantamine 13.2.2 NMDA Antagonist 13.2.3 Miscellaneous 13.2.3.1 Piracetam 13.2.3.2 Pyritinol 13.2.3.3 Dihydroergotoxine 13.2.3.4 Citicoline 13.2.3.5 Ginkgo biloba 13.3 Psychostimulants 13.3.1 Methylxanthines 13.3.2 Reuptake Inhibitors 13.3.2.1 Cocaine 13.3.2.2 Amphetamine 13.3.2.3 Methylphenidate 13.3.2.4 Modafinil 13.3.2.5 Atomoxetine 13.4 Psychedelic Drugs 13.4.1 Indole Amines 13.4.1.1 Lysergic Acid Diethylamide (LSD) 13.4.1.2 Psilocybin 13.4.2 Phenylalkyl Amine 13.4.2.1 Methylenedioxymethamphetamine (MDMA, `Ecstasy´) 13.4.3 Arylcyclohexyl Amine 13.4.3.1 Phencyclidine 13.4.4 Cannabinoids 13.4.4.1 Marijuana 13.4.4.2 Synthetic Cannabinoids Bibliography 14: Drug Dependence and Abuse 14.1 Ethanol 14.1.1 Acute Intoxication 14.1.2 Long-Term Complications 14.1.3 Treatment of Alcohol Dependence 14.2 Nicotine 14.2.1 Pharmacology 14.2.2 Treatment 14.3 Cannabinoids 14.3.1 Symptoms of Cannabis Abuse Bibliography 15: Local Anesthetics 15.1 Introduction and Historical Overview 15.2 Chemical Properties of Local Anesthetics 15.3 Clinical Classification of Local Anesthetics 15.4 Mechanism of Action of Local Anesthetics 15.5 Pharmacological Actions of Local Anesthetics 15.5.1 Local Actions 15.5.2 Systemic Actions 15.5.2.1 CNS Effects 15.5.2.2 CVS Effects 15.6 Pharmacokinetics of Local Anesthetics 15.7 Adverse Effects of Local Anesthetics 15.8 Drug Interactions 15.9 Techniques of Local Anesthesia (Box 15.1) Box 15.1 Overview of Local Anesthesia Techniques 15.10 Key Features of Individual Local Anesthetic Agents 15.10.1 Cocaine 15.10.2 Lignocaine 15.10.3 Bupivacaine 15.10.4 Other Agents 15.11 Recent Advances in Local Anesthesia Bibliography 16: Skeletal Muscle Relaxants 16.1 Introduction 16.2 Peripherally Acting Muscle Relaxants 16.2.1 Non-Depolarizing Blockers 16.2.2 Depolarizing Blockers 16.2.3 Monitoring the Depth of Neuromuscular Block 16.3 Centrally Acting Muscle Relaxants 16.3.1 Mephenesin Group 16.3.2 Benzodiazepines 16.3.3 GABA Derivative 16.3.4 Central Alpha 2 Agonist 16.3.5 Other Centrally Acting Muscle Relaxants 16.4 Directly Acting Muscle Relaxants 16.5 Miscellaneous 16.5.1 Botulinum Toxin Type A and B 16.5.2 Other Drugs Bibliography Part III: Autacoids and Other Chemical Mediators 17: Histamine, Serotonin, Bradykinin, and the Ergot Alkaloids 17.1 Histamine 17.1.1 Structure and Chemistry 17.1.2 Biosynthesis and Catabolism 17.1.3 Distribution, Release, and Receptors 17.1.4 Physiopathological and Pharmacological Effects 17.1.4.1 Cardiovascular System 17.1.4.2 Nervous System 17.1.4.3 Gastrointestinal System 17.1.4.4 Bronchiolar Smooth Muscle 17.1.5 Antihistamines 17.2 Serotonin 17.2.1 Structure and Chemistry 17.2.2 Biosynthesis, Release, and Catabolism 17.2.3 Distribution and Receptors 17.2.4 Physiopathological and Pharmacological Effects 17.2.4.1 Central Nervous System 17.2.4.2 Cardiovascular System 17.2.4.3 Gastrointestinal System 17.2.4.4 Miscellaneous Effects Serotonin Syndrome 17.2.5 Migraine Pharmacotherapy 17.2.5.1 Migraine Pathophysiology 17.2.5.2 Migraine Therapy Triptans Ditans Gepants Ergot Alkaloids Nonsteroidal Anti-Inflammatory Drugs Antiemetics Migraine Prophylaxis β-Adrenergic Blockers Anticonvulsants Antidepressants Calcium Channel Blockers Methysergide Anti-CGRP Monoclonal Antibodies 17.3 Bradykinin 17.3.1 Structure and Chemistry 17.3.2 Biosynthesis and Metabolism 17.3.3 Receptors 17.3.4 Physiopathological Effects 17.3.4.1 Cardiovascular System 17.3.4.2 Pain and Inflammation 17.3.4.3 Respiratory System 17.3.4.4 Renal System 17.3.5 Therapeutic Applications 17.4 Ergot Alkaloids 17.4.1 Therapeutic Effects 17.4.2 Adverse Effects Bibliography 18: Prostaglandins, Leukotrienes, and Related Compounds 18.1 Prostaglandins 18.1.1 History 18.1.2 Chemistry of Prostaglandins 18.1.3 Biosynthesis of Prostaglandins 18.1.4 Metabolism of Prostaglandins and Thromboxanes 18.1.5 Prostaglandin Receptors and Their Physiological Actions 18.1.6 Prostaglandin Analogs 18.2 Leukotrienes 18.2.1 Biosynthesis of Leukotrienes 18.2.2 Metabolism of Leukotrienes 18.2.3 Leukotriene Receptors and Its Physiological Action 18.2.4 Inhibitors of Leukotrienes 18.3 Platelet-Activating Factor (PAF) 18.4 Levuglandins (LGs) 18.5 Prostamides (PMs) 18.6 Esterified Eicosanoids Bibliography 19: Non-Steroidal Anti-Inflammatory Medicines 19.1 Introduction 19.2 Mechanism of Action 19.3 Classification 19.3.1 Chemical Classification 19.3.2 Clinical Classification 19.4 Comparison of NSAIMs Based on Clinical Classification 19.5 Clinical Pharmacology of NSAIMs 19.5.1 NSAIMs in the Geriatric Population 19.5.2 NSAIMs in Pediatrics Population 19.5.3 NSAIMs During Pregnancy 19.5.4 NSAIMs in Liver Disease 19.5.5 NSAIMs in Renal Disease 19.5.6 NSAIMs in Cardiac Patients Bibliography 20: Drug Used in Rheumatoid Arthritis 20.1 Pathophysiology 20.2 Management 20.2.1 Non-Steroidal Anti-Inflammatory Medicines (NSAIMs) 20.2.2 Corticosteroids 20.2.3 Methotrexate (MTX) 20.2.3.1 Side-Effects 20.2.4 Sulfasalazine (SSZ) 20.2.4.1 Side-Effects 20.2.5 Chloroquine and Hydroxychloroquine (HCQ) 20.2.5.1 Mechanisms 20.2.5.2 Side-Effects 20.2.6 Leflunomide (LEF) 20.2.7 Gold Salts 20.2.8 Immunosuppressants: Cyclosporine, Azathioprine 20.2.9 Tumor Necrosis Factor-Alpha (TNFα) Inhibitors 20.2.9.1 Side-Effects 20.2.10 Non-TNF Alpha Inhibitor Biologics 20.2.11 Tofacitinib 20.2.11.1 Side-Effects 20.3 Key Points on Usage of DMARDs Bibliography 21: Pharmacotherapy of Gout 21.1 Introduction 21.2 Aetiology and Risk Factors 21.3 Pathophysiology of Gout 21.4 Clinical Features of Gout 21.4.1 Asymptomatic Stage 21.4.2 Acute Gout 21.4.3 Inter-Critical Stage 21.4.4 Chronic Gout 21.5 Investigation and Diagnosis 21.5.1 Laboratory Investigations 21.5.2 Diagnostic Criteria 21.6 Drugs Used in the Treatment of Gout 21.6.1 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 21.6.2 Colchicine 21.6.3 Corticosteroids 21.6.4 Urate Lowering Agents 21.6.4.1 Allopurinol 21.6.4.2 Febuxostat 21.6.4.3 Probenecid 21.6.4.4 Sulfinpyrazone and Benzbromarone 21.6.4.5 Lesinurad 21.6.5 Uricase 21.6.5.1 Pegloticase 21.6.5.2 Rasburicase 21.7 Management of Gout 21.7.1 Non-Pharmacological Treatment 21.7.2 Pharmacological Treatment 21.7.2.1 Asymptomatic Hyperuricaemia 21.7.2.2 Treatment of Acute Gouty Attack 21.7.2.3 Prophylaxis for Prevention of Acute Flares 21.7.2.4 Urate Lowering Therapy (ULT) 21.8 Drugs in the Pipeline 21.8.1 Interleukin-1 Antagonist 21.8.2 Arhalofenate 21.8.3 Verinurad 21.8.4 Pegsiticase 21.8.5 Tranilast 21.8.6 Levotofisospam 21.8.7 Ulodesine Bibliography 22: Nitric Oxide, Vasoactive Peptides, and Purines 22.1 Nitric Oxide: Introduction Box 22.1 Overview of agents related to Nitric oxide (NO) 22.2 Functions of NO 22.2.1 Smooth Muscle 22.2.2 Cell Adhesion 22.2.3 Inflammation 22.2.4 Others 22.3 NO Synthase (NOS) 22.4 NO Donors 22.5 Vasoactive Peptides: Introduction 22.6 Peptide Antagonists 22.7 Peptide Receptors 22.8 Peptides with Their Vasoactive Properties 22.8.1 Angiotensins 22.8.2 Cholecystokinin (CCK) 22.8.3 Vasoactive Intestinal Peptide (VIP) 22.8.4 Somatostatin 22.8.5 Substance P 22.8.6 Neurotensin (NT) 22.8.7 Opioid Peptides 22.8.8 Oxytocin (OT) 22.8.9 Parathyroid Hormone (PTH) 22.8.10 Prolactin 22.8.11 Thyrotropin-Releasing Hormone (TRH) 22.8.12 Urotensin I 22.8.13 Vasopressin 22.9 Purines: Introduction 22.10 Importance of Purines 22.11 Purine Catabolism 22.12 Biological Activities of Purine Analogues 22.12.1 Anti-Leishmanial Activity 22.12.2 Antiviral Activity 22.12.3 Antifungal Activity 22.12.4 Antibacterial Activity 22.12.5 Antitumor Activity 22.12.6 Antiprotozoal Activity Bibliography Part IV: Cardiovascular and Renal Pharmacology 23: Drugs Affecting Renal Excretory Function 23.1 Carbonic Anhydrase Inhibitors 23.1.1 Mechanism of Action 23.1.2 Clinical Effects 23.1.3 Therapeutic Uses 23.1.4 Adverse Drug Reactions 23.2 Osmotic Diuretics 23.2.1 Mechanism of Action 23.2.2 Therapeutic Uses 23.2.3 Adverse Drug Reactions 23.3 Na+-K+-2Cl- Symport Inhibitors 23.3.1 Mechanism of Action 23.3.2 Clinical Effects of Loop Diuretics 23.3.3 High-Ceiling Diuretics 23.3.4 Relevant Pharmacokinetics 23.3.5 Special Properties of Torsemide that Are Beneficial Clinically 23.3.6 Therapeutic Uses 23.3.7 Adverse Drug Reactions 23.3.8 Drug Interactions (Box 23.1) Box 23.1 Drug Interactions of Loop Diuretics 23.4 Na+-Cl- Symporter Inhibitors 23.4.1 Mechanism of Action 23.4.2 Clinical Effects of Thiazide Diuretics 23.4.3 Differences Between Hydrochlorothiazide, Chlorthalidone and Indapamide 23.4.4 Therapeutic Uses 23.4.5 Adverse Drug Reactions 23.5 Renal Epithelial Na+ Channel Inhibitors 23.5.1 Mechanism of Action 23.5.2 Clinical Effects of ENaC Inhibitors 23.5.3 Therapeutic Uses 23.5.4 Adverse Drug Reactions 23.6 Aldosterone Antagonists 23.6.1 Mechanism of Action 23.6.2 Clinical Effects 23.6.3 Relevant Pharmacokinetics 23.6.4 Therapeutic Uses 23.6.5 Adverse Drug Reactions 23.7 Natriuretic Peptides 23.7.1 Mechanism of Action 23.7.2 Clinical Effects of Nesiritide 23.8 Adenosine Receptor Antagonists 23.9 Vasopressin Receptor Agonists 23.9.1 Therapeutic Uses of Vasopressin 23.9.2 Adverse Drug Reaction to Vasopressin 23.9.3 Use of Nitroglycerin with Vasopressin 23.9.4 Uses of Desmopressin 23.9.5 Adverse Drug Reactions to Desmopressin 23.9.6 Drugs Affecting Vasopressin Response in the Kidneys 23.10 Vasopressin Antagonists 23.11 Clinical Pharmacology of Diuretic Use 23.11.1 Diuretic Braking 23.11.2 Use in Chronic Renal Disease 23.11.3 Treatment of Oedema 23.11.4 Diuretics in Acute Renal Failure Bibliography 24: Antihypertensive Agents 24.1 Introduction 24.2 ACE Inhibitors (ACEIs) 24.3 Angiotensin-II Type 1-Receptor b\Blockers (ARBs) 24.4 Calcium Channel Blockers (CCBs) 24.5 Diuretics 24.6 Beta-Blockers 24.7 Less Commonly Used Antihypertensive Agents 24.7.1 Alpha-1 Adrenergic Blockers 24.7.2 Centrally Acting Sympatholytic Drugs 24.7.3 Direct Vasodilators 24.7.4 Direct Renin Inhibitors 24.8 Antihypertensive Agents of Choice in the Different Subpopulation 24.9 Management of Hypertensive Emergencies Bibliography 25: Treatment of Ischemic Heart Disease 25.1 Introduction 25.2 Pathophysiology of IHD Box 25.1 Factors Associated with Myocardial Imbalance 25.3 Clinical Features of IHD 25.4 Principles of IHD Treatment 25.5 Treatment Strategies for IHD 25.5.1 Organic Nitrates 25.5.2 Beta-Adrenoceptor Antagonists (beta-Blockers) 25.5.3 Calcium Channel Blockers 25.5.4 Potassium Channel Openers 25.5.5 Specific Sinus Node Inhibitors 25.5.6 Late Sodium Current Inhibitors 25.6 Surgical Therapy for IHD Bibliography 26: Drugs Used in Heart Failure 26.1 Pathophysiology 26.2 Treatment of Congestive Heart Failure 26.2.1 Diuretics 26.2.1.1 Loop Diuretics (Furosemide, Torsemide, Ethacrynic Acid, Bumetanide) 26.2.1.2 Thiazides (Hydrochlorothiazide, Chlorthalidone, Indapamide) 26.2.1.3 Potassium Sparing Diuretics 26.2.1.4 Diuretic Resistance 26.2.2 Angiotensin Converting Enzyme Inhibitors (ACEIs) 26.2.3 Beta-Blockers 26.2.4 Digoxin 26.2.5 Nitrates 26.2.6 Atrial Natriuretic Peptide and Vasopeptidase Inhibitors Box 26.1 Mortality Reducing Drugs in CHF 26.3 Treatment of Severe Decompensated and Acute Heart Failure Bibliography 27: Drugs Used in Cardiac Arrhythmias 27.1 Introduction 27.2 Electrophysiology of the Heart 27.2.1 The Ventricular Action Potential 27.2.2 The Electrocardiogram 27.3 Pathophysiology of Cardiac Arrhythmias 27.3.1 Abnormality in Impulse Formation 27.3.2 Abnormality in Impulse Conduction 27.4 Pharmacology of the Antiarrhythmic Drugs 27.4.1 Classification of Antiarrhythmic Drugs 27.4.2 Specific Antiarrhythmic Drugs 27.5 Therapeutic Use of Antiarrhythmic Drugs 27.5.1 Guiding Principles for Antiarrhythmic Drug Use 27.5.2 Non-Pharmacological Therapies 27.6 Conclusion Bibliography 28: Pharmacotherapy of Shock and Drugs Used in Cardiopulmonary Resuscitation 28.1 Pharmacotherapy of Shock 28.1.1 Types of Shock Box 28.1 Major Types and Related Causes of Shock 28.1.2 Principles of Shock Management 28.1.3 Fluid Management in Shock 28.1.3.1 Crystalloid Fluids/Plasma Substitutes 28.1.3.2 Colloidal Fluids/Plasma Substitutes Box 28.2 Similarities and Differences Among the Colloidal Plasma Substitutes 28.1.3.3 Whole Blood, Blood Products, and Plasma 28.1.4 Inotropes in Shock 28.1.5 Type-Specific Management of Shock Box 28.3 Management Protocols for Different Types of Shock 28.2 Drugs Used in Cardiopulmonary Resuscitation Bibliography 29: Pharmacotherapy of Pulmonary Arterial Hypertension 29.1 Introduction 29.2 Endothelin-1 Receptor Antagonists 29.3 Drugs Targeting Nitric Oxide Pathway 29.3.1 Phosphodiesterase-5 Inhibitors 29.3.2 Soluble Guanylate Cyclase Stimulators 29.4 Drugs Targeting Prostacyclin Pathway 29.5 Approach to a Patient with PAH Bibliography 30: Antiplatelets, Anticoagulants, and Fibrinolytics 30.1 Hemostasis 30.1.1 Primary Hemostasis 30.1.2 Secondary Hemostasis 30.1.3 Fibrinolysis 30.2 Antiplatelet Drugs 30.2.1 Aspirin 30.2.2 Clopidogrel 30.2.3 Prasugrel 30.2.4 Ticagrelor and Cangrelor 30.2.5 Abciximab, Eptifibatide, and Tirofiban 30.2.6 Vorapaxar 30.2.7 Dipyridamole and Cilostazol 30.2.8 Adverse Effects, Complications, and Contraindications of Antiplatelet Drugs 30.3 Anticoagulants 30.3.1 Heparin and Other Indirect Thrombin Inhibitors 30.3.2 Warfarin and Other Vitamin K Antagonists 30.3.3 Direct Thrombin Inhibitors 30.3.4 Adverse Effects, Complications, and Contraindications of Anticoagulant Drugs 30.4 Fibrinolytics 30.4.1 Recombinant T-PA and Its Variants 30.4.2 Adverse Effects, Complications, and Contraindications of Fibrinolytic Drugs 30.5 Conclusion Bibliography 31: Drugs Used inDyslipidemia 31.1 Introduction 31.2 Biochemistry of Lipoproteins 31.3 Statins 31.3.1 Mechanism of Action 31.3.2 Effects on Lipids 31.3.3 Pleiotropic Effects of Statins 31.3.4 Adverse Effects 31.3.5 Drug Interaction 31.3.6 Clinical Use 31.4 Fibrates 31.4.1 Mechanism of Action 31.4.2 Effect on Lipids 31.4.3 Other Effects of Fibrates 31.4.4 Adverse Effects and Contraindication 31.4.5 Drug Interaction 31.4.6 Uses 31.5 Niacin 31.5.1 Mechanism of Action 31.5.2 Effect on Lipoproteins 31.5.3 Pharmacokinetics 31.5.4 Adverse Effect 31.5.5 Use 31.6 Acipimox 31.7 Bile Acid Sequestrants 31.8 Ezetimibe 31.9 Mipomersen 31.10 Lomitapide 31.11 PCSK9 Inhibitors 31.12 Gugulipid 31.13 Other Hypolipidemic Agents Developed but Withdrawn/Failure 31.14 Clinical Pharmacology Bibliography Part V: Pulmonary Pharmacology 32: Treatment of Asthma and COPD 32.1 Pathophysiology of Asthma and COPD 32.1.1 Clinical Presentation 32.2 Routes of Drug Administration in Asthma and Pulmonary Diseases 32.3 Drug Classes 32.3.1 Beta-2 Agonists 32.3.2 Corticosteroids 32.3.3 Muscarinic Antagonists 32.3.4 Leukotriene Inhibitors 32.3.5 Methylxanthines and Phosphodiesterase Inhibitors 32.3.6 Mast Cell Stabilizers 32.3.7 Monoclonal Antibody 32.4 Stepwise Management of Bronchial Asthma (Fig. 32.4) 32.5 Management of COPD Bibliography 33: Drugs Used in Cough and Rhinitis 33.1 Cough 33.1.1 Drugs for Cough Management 33.1.1.1 Antitussives 33.1.1.2 Expectorants (Mucokinetics) 33.1.1.3 Mucolytics 33.1.1.4 Demulcents 33.1.2 Treatment of Specific Types of Cough 33.2 Rhinitis 33.2.1 Drugs for Rhinitis Bibiliography Part VI: Gastrointestinal Pharmacology 34: Drugs Used in Acid Peptic Disorders 34.1 Introduction 34.2 Physiology of Acid Secretion and Mucosal Defense Mechanism 34.3 Drugs Used in the Management of Peptic Ulcer 34.3.1 Antacids 34.3.2 Prostaglandin Analogs 34.3.3 Ulcer Protectants 34.3.4 Histamine Receptor (H2) Blockers 34.3.5 Proton Pump Inhibitors (PPIs) 34.3.6 Potassium-Competitive Acid Blockers (P-CAB) 34.3.7 Anti-H. pylori Drugs 34.3.8 Obsolete Anti-Ulcer Drugs 34.3.9 Clinical Pharmacology Bibliography 35: Drugs Affecting Gastrointestinal Motility 35.1 Introduction 35.2 Regulation of Gastrointestinal Motility by the Enteric Nervous System Box 35.1: Classification of Drugs Affecting Gastrointestinal Motility 35.3 Prokinetic Agents 35.3.1 Dopamine Receptor Antagonists 35.3.2 Serotonin Receptor Agonists 35.3.3 Motilin and Macrolide Antibiotics 35.3.4 Miscellaneous Agents for Stimulating GI Motility 35.4 Agents Suppressing GI Motility Bibliography 36: Antiemetics 36.1 Introduction 36.2 Pathophysiology of Emesis 36.3 Pathophysiology of Nausea: An Entity Distinct from Emesis 36.4 Classification of Antiemetics Box 36.1: Classification of Antiemetics 36.4.1 5HT3 Receptor Antagonists 36.4.2 D2 Dopamine Receptor Blockers 36.4.3 Anticholinergic Agents 36.4.4 Antihistamines 36.4.5 Neurokinin (NK1) Receptor Antagonists 36.4.6 Cannabinoids 36.4.6.1 Dronabinol (Delta-9-Tetrahydrocannabinol, THC) 36.4.6.2 Nabilone 36.4.7 Glucocorticoids 36.4.8 Benzodiazepines Bibliography 37: Drug Therapy for Constipation 37.1 Introduction 37.2 Mechanism and Etiology of Constipation 37.3 Drugs for Constipation 37.4 Bulk Forming Agents 37.4.1 Bran 37.4.2 Psyllium (Ispaghula) 37.4.3 Methylcellulose 37.5 Stool Softeners (Emollients) 37.5.1 Liquid Paraffin (Mineral Oil) 37.5.2 Dioctyl Sulfosuccinate (DOSS or Docusate) 37.6 Stimulant Purgatives 37.6.1 Bisacodyl 37.6.2 Sodium Picosulfate 37.6.3 Senna and Cascara 37.6.4 Castor Oil 37.7 Osmotic Purgatives (Salts and Lactulose) 37.8 Prokinetics 37.8.1 Prucalopride and Cisapride (5-HT4 Receptors Agonists) 37.8.2 Macrolide Antibiotics (Motilin Agonists) 37.8.3 mu-Opioid Receptor Antagonists 37.9 Active Secretors 37.9.1 Prostaglandin Analogue (Lubiprostone) 37.9.2 Membrane Spanning Guanylate Cyclase-C Receptor Agonists: Linaclotide and Plecanatide 37.10 Clinical Pharmacology Bibliography 38: Antidiarrheal Agents 38.1 General Definition of Diarrhea 38.2 General Principles in the Treatment of Diarrhea 38.3 Inhibition of Intestinal Motility-Antisecretory Drugs 38.3.1 Opioids 38.3.2 Octreotide and Somatostatin 38.3.3 Enkephalinase Inhibitors 38.3.4 Alpha 2 Agonists 38.3.5 5HT3 Receptor Antagonists 38.3.6 Apical Chloride Channel Inhibitor 38.3.7 Bismuth Subsalicylate 38.3.8 Zinc 38.4 Intraluminal Agents 38.4.1 Clays 38.4.2 Bile Salt Binding Resins 38.4.3 Fiber 38.5 Pro-Absorptive Agents 38.5.1 Teduglutide 38.6 Oral Rehydration Solution 38.7 Treatment of Specific Diarrhea 38.7.1 Secretory Diarrhea in Tumors [Like Carcinoid Syndrome, VIPomas] 38.7.2 Drugs That Are Used in Traveler´s Diarrhea Bibliography 39: Irritable Bowel Syndrome 39.1 Introduction 39.2 Pathophysiology 39.3 Pharmacotherapy of IBS 39.3.1 Current Pharmacological Treatment for IBS 39.3.1.1 Medications for Abdominal Pain 39.3.1.2 Medications for Diarrhea 39.3.1.3 Medications for Constipation 39.3.1.4 Anti-inflammatory Approaches 39.3.2 Newer Drugs Under Study for IBS Box 39.1 Medications Used in Management of Irritable Bowel Syndrome Bibliography 40: Pharmacotherapy of Inflammatory Bowel Disease 40.1 Introduction 40.2 Pharmacological Management of IBD 40.2.1 Aminosalicylates 40.2.2 Corticosteroids 40.2.3 Thiopurines 40.2.4 Methotrexate and Cyclosporine 40.2.5 Novel Therapies for IBD 40.2.5.1 TNF-alpha Inhibitors 40.2.5.2 Anti-IL-12/IL-23 Agents 40.2.5.3 Selective Anti-IL-23 Agents 40.2.5.4 Anti-IL-17 Agents 40.2.5.5 Anti-Adhesion Agents 40.2.5.6 Antibiotics and Probiotics 40.2.5.7 Other Modalities of Pharmacological Management Bibliography 41: Miscellaneous Drugs Acting on the Gastrointestinal System 41.1 Appetite Stimulants or Orexigenic Drugs 41.1.1 Alcohol as Appetite Stimulant 41.1.2 Drugs as Appetite Stimulants 41.2 Digestants 41.2.1 Pharmacokinetics of Digestants 41.2.2 Scope of Digestants 41.2.3 Adverse Effects of Digestants 41.3 Anti-Flatulence Drugs and Carminatives Bibliography Part VII: Endocrine Pharmacology 42: Hypothalamic and Pituitary Hormones 42.1 Introduction 42.2 Anatomy of Hypothalamus-Pituitary Box 42.1 Classification of Endocrine Hormones Based on the Site of Secretion Box 42.2 Classification of Hormones Based on Its Site of Binding 42.3 Physiology of Hypothalamus-Pituitary-Organ Axis 42.4 Pathophysiology of Hypothalamus-Pituitary 42.5 Drugs Affecting the Hypothalamus-Pituitary-Organ Axis 42.5.1 Somatostatin Analogues 42.5.2 Pegvisomant 42.5.3 Growth Hormone (Somatropin) 42.5.4 Mecasermin 42.5.5 Drugs for Hyperprolactinemia 42.5.6 GnRH Agonists Box 42.3 Various Formulations of GnRH Analogues Box 42.4 Indications for Pulsatile and Non-pulsatile GnRH Therapy 42.5.7 GnRH Antagonists 42.5.8 Recombinant Gonadotropins 42.5.9 Oxytocin 42.5.10 Vasopressin Box 42.5 Characteristic Features of Vasopressin and Desmopressin 42.5.11 Vasopressin Antagonists Box 42.6 Characteristic Features of Conivaptan and Tolvaptan 42.5.12 ACTH 42.5.13 TSH Bibliography 43: Pharmacotherapy of Diabetes Mellitus 43.1 Introduction 43.2 Classification of Diabetes and Diabetes Clusters 43.3 Screening and Diagnosis of DM 43.4 Pathophysiology of Hyperglycemia 43.5 Treatment of DM 43.5.1 Management of Type 1 DM Box 43.1 Sources of Animal Insulins Box 43.2 Spectrum of Actions of Insulins 43.5.2 Management of Type 2 DM 43.5.2.1 Guideline Recommendations for T2DM Management 43.5.3 Gestational Diabetes Mellitus (GDM) Bibliography 44: Thyroid and Antithyroid Drugs 44.1 Introduction 44.2 Thyroid Hormone Chemistry and Biosynthesis Box 44.1 Major Processes Involved in the Synthesis, Storage, and Secretion of T3 and T4 44.2.1 Iodide Uptake 44.2.2 Oxidation and Iodination 44.2.3 Formation of T4 and T3 from Iodotyrosines (Coupling) 44.2.4 Secretion of Thyroid Hormones 44.2.5 Peripheral Conversion of T4 to T3 44.3 Transport, Metabolism, and Excretion of Thyroid Hormones 44.4 Regulation of Thyroid Hormone Secretion (Fig. 44.2) 44.5 Mechanism of Action of Thyroid Hormone 44.6 Pharmacological Actions of Thyroid Hormone 44.6.1 Growth and Development 44.6.2 Thermogenic Effects 44.6.3 Cardiovascular Effects 44.6.4 Metabolic Effects 44.7 Thyroid Hormone Preparations 44.7.1 Pharmacokinetics of Thyroid Hormone Preparations 44.7.2 Uses of Thyroid Hormone Preparations 44.7.3 Adverse Effects of Thyroid Hormone Preparations 44.8 Antithyroid Drugs and Other Thyroid Inhibitors 44.8.1 Antithyroid Drugs (Thioamides) Box 44.2 Treatment of Thyroid Storm 44.8.2 Ionic Inhibitors 44.8.3 Iodine and Iodides (Hormone Release Inhibitors) 44.8.4 Radioactive Iodine (Destroyers of Thyroid Tissue) Bibliography 45: Adrenocorticosteroids and Their Antagonists 45.1 Introduction 45.2 Biosynthesis of Adrenocortical Hormones 45.3 Regulation of Adrenocortical Hormone Secretion 45.4 Pharmacological Actions of Adrenocortical Hormones 45.5 Mechanism of Action at the Cellular Level 45.6 Glucocorticoid and Mineralocorticoid Preparations 45.7 Pharmacokinetics of Steroids 45.8 Uses of Steroids 45.9 Adverse Effects of Steroids 45.10 Contraindications of Steroids 45.11 Inhibitors of ACTH Secretion, Steroidogenesis and Antagonists of Glucocorticoids and Mineralocorticoids 45.11.1 Inhibitors of ACTH Secretion 45.11.2 Inhibitors of Steroidogenesis 45.11.3 Glucocorticoid Antagonist 45.11.4 Mineralocorticoid Antagonists Bibliography 46: Gonadal Hormones and Their Inhibitors 46.1 Introduction Box 46.1 Sites of Synthesis of Gonadal Hormones (Estrogens, Progestins, and Androgens) 46.1.1 Estrogens Box 46.2 Classification of Estrogens Box 46.3 Preferred Dose of Estrogens (Ethinyl Estradiol) in Different Settings 46.1.2 Actions of Estrogens 46.1.3 Mechanism of Action of Estrogens 46.1.4 Pharmacokinetics of Estrogens 46.1.5 Adverse Drug Reactions Related to Estrogens 46.1.6 Clinical Indications of Estrogens 46.2 Antiestrogens Box 46.4 Classification of Estrogen Synthesis Inhibitors (Aromatase Inhibitors) Box 46.5 Classification of Antioestrogens 46.2.1 Clomiphene Citrate 46.2.2 Fulvestrant 46.2.3 Letrozole 46.3 Selective Estrogen Receptor Modulators (SERMs) Box 46.6 Classification of Selective Estrogen Receptor Modulators (SERMs) 46.3.1 Tamoxifen Citrate 46.3.2 Raloxifene 46.4 Progestins Box 46.7 Classification of Progestins/Progestational Agents/Progestagens/Progestogens/Gestagens/Gestogens 46.4.1 Actions of Progestins Box 46.8 Progestins with Androgenic Actions 46.4.2 Mechanism of Action of Progestins 46.4.3 Pharmacokinetics of Progestins 46.4.4 Adverse Drug Reactions Related to Progestins 46.4.5 Clinical Indications of Progestins 46.5 Antiprogestins Box 46.9 Classification of Antiprogestins 46.5.1 Mifepristone 46.5.2 Ulipristal 46.6 Birth Controlling Measures in Females 46.6.1 Oral Contraceptive Pills (OCPs) Box 46.10 Overview of Preparations of Oral Contraceptive Pills (OCPs) Box 46.11 Mechanism of Action of Oral Contraceptive Pills (OCPs) Box 46.12 ADRs Associated with Estrogen and Progestin Components in OCPs Box 46.13 Incidence of Thromboembolic Events Box 46.14 Major Risks and Benefits of Oral Contraceptive Pills (OCPs) [Containing Both The Components (Estrogens and Progestin... Box 46.15 Mechanism of Common ADRs Associated with Both Components (Estrogen and Progestin) in OCPs Box 46.16 Contraindications of Oral Contraceptive Pills (OCPs) Box 46.17 Salient Updates on Hormone Replacement Therapy (HRT) 46.7 Androgens Box 46.18 Classification of Androgens 46.7.1 Androgen Actions 46.7.2 Mechanism of Action 46.7.3 Pharmacokinetics of Androgens 46.7.4 Adverse Drug Reactions Related to Androgens 46.7.5 Clinical Indications of Androgens 46.8 Antiandrogens Box 46.19 Classification of Antiandrogens 46.9 Conclusion Bibliography 47: Pharmacotherapy of Obesity 47.1 Introduction 47.2 Physiology of Appetite and Satiety 47.3 Drugs Used to Treat Obesity 47.3.1 Lorcaserin 47.3.2 Phentermine and Phentermine-Topiramate Fixed Drug Combination (FDC) 47.3.3 Liraglutide 47.3.4 Naltrexone-Bupropion FDC 47.3.5 Orlistat 47.3.6 Obsolete Drugs Used for Obesity 47.4 Clinical Pharmacology Bibliography 48: Drugs Affecting Bone Mineral Homeostasis 48.1 Introduction 48.2 Hormonal Regulation of Bone Mineral Homeostasis 48.2.1 Vitamin D Box 48.1 Management of Vitamin D Deficiency and Insufficiency 48.2.2 Parathormone (PTH) 48.2.3 Calcitonin 48.2.4 Glucocorticoids 48.2.5 Estrogens 48.3 Non-Hormonal Agents Regulating Bone Mineral Homeostasis 48.3.1 Bisphosphonates 48.3.2 Denosumab Bibliography Part VIII: Hematopoietic System 49: Pharmacotherapy of Iron Deficiency and Other Related Anaemia 49.1 Brief Pathogenesis 49.2 Therapeutic Objectives 49.3 Oral Iron Therapy Box 49.1 Oral Iron Preparations 49.3.1 Pharmacokinetics 49.3.2 Dosage Calculation 49.3.3 Adverse Effects of Oral Iron Therapy 49.4 Parenteral Iron Therapy 49.4.1 Indications of Parenteral Iron Therapy 49.4.2 Preparations for Parenteral Use Box 49.2 Parenteral Iron Preparations 49.4.3 Calculating the Dose Required 49.4.4 Adverse Drug Reactions 49.5 Long-Term Considerations of Iron Therapy 49.6 Key Principles in Pharmacotherapy of Iron Deficiency of Anaemia 49.7 Treatment of Hypoproliferative Anaemia 49.7.1 Erythropoietin (Erythropoiesis Stimulating Agents) Bibliography 50: Pharmacotherapy of Vitamin B12 and Folic Acid Deficiency 50.1 Introduction 50.2 Vitamin B12 (Cobalamin) 50.2.1 Chemistry 50.2.2 Source and Requirements 50.2.3 Absorption, Transport, and Storage 50.2.4 Biochemical Role 50.2.5 Drugs Causing Cobalamin Deficiency 50.2.6 Preparations of Cobalamin 50.2.7 Uses of Cobalamin 50.3 Folic Acid 50.3.1 Chemistry 50.3.2 Absorption and Excretion 50.3.3 Biochemical Role of THFA 50.3.4 Source and Daily Requirements 50.3.5 Drugs Interfering with Folate Metabolism 50.3.6 Uses 50.4 Clinical Pharmacology Bibliography 51: Drug-Induced Blood Dyscrasias 51.1 Hemolytic Anemia (Borham 2018) 51.1.1 Immune-Mediated Haemolytic Anemia (IHA) 51.1.2 Non-Immune-Mediated Hemolytic Anemia (Borham 2018) 51.2 Aplastic Anemia (Qahtani 2018) Box 51.1 Drugs Causing Aplastic Anemia 51.3 Megaloblastic Anemia (Qahtani 2018; Borham 2018) 51.4 Sideroblastic Anemia (Mintzer et al. 2009) Box 51.2 Drugs Causing Sideroblastic Anemia 51.5 Methemoglobinemia (Mintzer et al. 2009) Box 51.3 Drugs Causing Methemoglobinemia 51.6 Pure Red Cell Aplasia (Mintzer et al. 2009) Box 51.4 Drugs Causing Pure Red Cell Aplasia 51.7 Immune Thrombocytopenia (Mintzer et al. 2009) Box 51.5 Drugs Associated with Immune Thrombocytopenia 51.8 Thrombotic Microangiopathies (Mintzer et al. 2009) Box 51.6 Drugs Associated with Thrombotic Microangiopathies 51.9 Hypercoagulability (Mintzer et al. 2009) Box 51.7 Drugs Causing Hypercoagulability 51.10 Hypoprothrombinemia (Mintzer et al. 2009) Box 51.8 Drugs Causing Hypoprothombinemia 51.11 Agranulocytosis/Neutropenia (Mintzer et al. 2009) 51.12 Neutrophilia (Mintzer et al. 2009) Box 51.9 Drugs Causing Neutrophilia 51.13 Eosinophilia (Mintzer et al. 2009) Box 51.10 Drugs Causing Eosinophilia 51.14 Polycythemia (Mintzer et al. 2009) 51.15 Myelodysplasia and Acute Leukemia (Mintzer et al. 2009) Box 51.11 Drugs Causing Myelodysplastic Syndrome Bibliography Part IX: Chemotherapy of Microbial Diseases 52: General Principles of Antimicrobial Therapy 52.1 Introduction 52.2 Classification of Antimicrobial Agents 52.3 Antibacterial Agents 52.3.1 Pharmacodynamic Parameters 52.3.2 Pharmacokinetic Parameters of Antimicrobial Therapy 52.3.3 Barriers to Drug Penetration 52.3.4 Concentration vs Time Dependent Killing 52.4 Antiviral Agents 52.5 Antifungal and Antiprotozoal Agents 52.6 Selection of Appropriate Antimicrobial Agents 52.7 Types of Antimicrobial Therapy (Fig. 52.3) 52.7.1 Chemoprophylaxis 52.7.1.1 Immunocompromised Patients 52.7.1.2 Surgical Prophylaxis 52.7.1.3 Prophylaxis for Infective Endocarditis 52.7.1.4 Pre- and Post-Exposure Prophylaxis 52.7.1.5 Suppressive Prophylaxis 52.7.2 Empirical Treatment 52.7.3 Definitive Therapy 52.8 Combination Therapy 52.9 Problems Encountered in Antimicrobial Therapy 52.9.1 Resistance to Therapy 52.9.1.1 Mechanism of Drug Resistance 52.9.1.2 Types of Drug Resistance 52.9.2 Adverse Drug Reactions 52.9.3 Super Infection and Masking of Infection Bibilography 53: Sulfonamides, Quinolones, and Agents for Urinary Tract Infections 53.1 Sulphonamides 53.1.1 Classification of Sulphonamides Box 53.1 Classification of Sulphonamides (Values in Parentheses Indicate the Half-Lives) 53.1.2 Chemical Nature of Sulphonamides 53.1.3 Mechanism of Action of Sulphonamides 53.1.4 Antibacterial Spectrum of Sulphonamides 53.1.5 Pharmacokinetics of Sulphonamides 53.1.6 Clinical Uses of Sulphonamides 53.1.7 Adverse Effects of Sulphonamides 53.1.8 Drugs Interactions of Sulphonamides 53.1.9 Sulphonamide Resistance 53.1.10 Key Points on Individual Sulphonamides Box 53.2 Characteristics of Individual Sulphonamide Agents 53.2 Cotrimoxazole/Trimethoprim-Sulphamethoxazole 53.2.1 Mechanism of Action of Cotrimoxazole 53.2.2 Antibacterial Spectrum of Cotrimoxazole 53.2.3 Clinical Uses of Cotrimoxazole 53.2.4 Adverse Effects of Cotrimoxazole 53.2.5 Cotrimoxazole Resistance 53.3 Quinolones 53.3.1 Mechanism of Action of Quinolones 53.3.2 Antibacterial Spectrum of Quinolones 53.3.3 Classification of Quinolones Box 53.3 Modern Classification of Quinolones 53.3.4 Pharmacokinetics of Quinolones 53.3.5 Clinical Uses of Quinolones 53.3.6 Adverse Effects of Quinolones 53.3.7 Quinolone Resistance 53.3.8 Key Points on Individual Quinolones Box 53.4 Characteristics of Individual Quinolone Agents 53.4 Other Agents for Urinary Tract Infections 53.4.1 Urinary Antiseptics 53.4.2 Urinary Analgesics Bibliography 54: Penicillins, Cephalosporins, and Other beta-Lactam Antibiotics 54.1 Penicillins 54.2 Cephalosporins and Cephamycins 54.2.1 First-Generation Cephalosporins 54.2.2 Second-Generation Cephalosporins 54.2.3 Third-Generation Cephalosporins 54.2.4 Fourth-Generation Cephalosporins 54.3 Carbapenams 54.4 Monobactams 54.5 Carbacepham 54.6 beta-Lactamase Inhibitors Bibliography 55: Protein Synthesis Inhibitors 55.1 Introduction 55.2 Aminoglycosides 55.2.1 Sources of Aminoglycosides Box 55.1 Sources of Aminoglycoside Antibiotics and their Nomemclature 55.2.2 Chemistry and Nomenclature 55.2.3 Mechanism of Action 55.2.4 Spectrum of Anti-Microbial Activity 55.2.5 Mechanism of Resistance 55.2.6 Salient Pharmacokinetic Features 55.2.7 Dosing and Monitoring 55.2.8 Therapeutic Uses 55.2.9 Adverse Effects 55.2.10 Salient Pharmacological Properties of Individual Aminoglycosides 55.3 Tetracyclines and Glycylcyclines 55.3.1 Sources of Tetracyclines and Glycylcyclines 55.3.2 Mechanism of Action 55.3.3 Spectrum of Anti-Microbial Activity 55.3.4 Mechanism of Resistance 55.3.5 Salient Pharmacokinetic Features 55.3.6 Dosing and Monitoring 55.3.7 Therapeutic Uses 55.3.8 Adverse Effects 55.4 Chloramphenicol 55.4.1 Mechanism of Action (Fig. 55.5) 55.4.2 Spectrum of Anti-Microbial Activity 55.4.3 Mechanism of Resistance 55.4.4 Salient Pharmacokinetic Features 55.4.5 Therapeutic Uses and Dosage 55.4.6 Adverse Effects 55.5 Macrolides and Ketolides 55.5.1 Mechanism of Action 55.5.2 Spectrum of Anti-Microbial Activity 55.5.3 Mechanism of Resistance 55.5.4 Salient Pharmacokinetic Features Box 55.2 Salient Pharmacokinetic Features of Various Macrolide and Ketolide Antibiotics 55.5.5 Therapeutic Uses and Dosage Box 55.3 Drug Dosages of Various Macrolide and Ketolide Antibiotics 55.5.6 Adverse Effects 55.5.7 Drug Interactions 55.6 Lincosamides 55.6.1 Mechanism of Action 55.6.2 Spectrum of Anti-Microbial Activity 55.6.3 Mechanism of Resistance 55.6.4 Salient Pharmacokinetic Features 55.6.5 Dosing 55.6.6 Therapeutic Uses 55.6.7 Adverse Effects 55.7 Streptogramins 55.7.1 Mechanism of Action 55.7.2 Spectrum of Anti-Microbial Activity 55.7.3 Mechanism of Resistance 55.7.4 Salient Pharmacokinetic Features 55.7.5 Therapeutic Uses and Dosage 55.7.6 Adverse Effects 55.7.7 Drug Interactions 55.8 Oxazolidinones 55.8.1 Mechanism of Action 55.8.2 Spectrum of Anti-Microbial Activity 55.8.3 Mechanism of Resistance 55.8.4 Salient Pharmacokinetic Features 55.8.5 Dosing 55.8.6 Therapeutic Uses 55.8.7 Adverse Effects 55.8.8 Drug Interactions 55.9 MiscellaneousDrugs 55.9.1 Spectinomycin 55.9.2 Mupirocin 55.9.3 Fusidic Acid 55.9.4 Pleuromutilins Bibliography 56: Antimycobacterial Drugs 56.1 Introduction 56.1.1 Epidemiology 56.1.2 Etiopathogenesis 56.1.3 Clinical Presentation 56.1.4 Diagnosis 56.1.4.1 Microscopy 56.1.4.2 Culture 56.1.4.3 Molecular Methods 56.1.4.4 Serology 56.1.4.5 Tuberculin Skin Test 56.1.4.6 Chest Radiography 56.1.5 Drugs for Tuberculosis 56.1.5.1 First-Line Antituberculosis Drugs 56.1.5.2 Second-Line Antituberculosis Drugs 56.1.5.3 Drug Susceptibility Testing (DST) 56.1.6 Treatment of Tuberculosis 56.1.6.1 Treatment of Drug-Resistant TB 56.1.6.2 Treatment of Extrapulmonary Tuberculosis 56.1.6.3 Treatment of Tuberculosis in HIV-Positive Persons 56.1.6.4 Treatment of TB in Pregnant or Lactating Women 56.1.6.5 Treatment of TB in Children 56.1.6.6 Treatment of Latent TB 56.1.7 Tuberculosis Infection Prevention and Control 56.2 Drugs for Leprosy 56.2.1 Epidemiology 56.2.2 Etiopathogenesis 56.2.3 Clinical Presentation 56.2.4 Diagnosis 56.2.5 Drugs for Leprosy 56.2.5.1 Multidrug Therapy (MDT) 56.2.5.2 Treatment of Leprosy Reactions 56.2.5.3 Chemoprophylaxis for Leprosy 56.3 Drugs for Nontuberculous Mycobacteria 56.4 Conclusion Bibliography 57: Antifungal Drugs 57.1 Introduction 57.2 Amphotericin B 57.2.1 Mechanism of Action 57.2.2 Pharmacokinetics 57.2.3 Spectrum of Activity 57.2.4 Therapeutic Uses 57.2.5 Adverse Effects 57.3 Imidazoles and Triazoles 57.3.1 Mechanism of Action 57.3.2 Pharmacokinetics 57.3.3 Spectrum of Activity 57.3.4 Therapeutic Uses 57.3.4.1 Fluconazole (Most Commonly Used Azole) 57.3.4.2 Itraconazole 57.3.4.3 Voriconazole 57.3.4.4 Posaconazole 57.3.4.5 Isavuconazole 57.3.5 Adverse Effects 57.3.5.1 Fluconazole 57.3.5.2 Itraconazole 57.3.5.3 Voriconazole 57.3.5.4 Posaconazole 57.3.5.5 Isavuconazole 57.4 Flucytosine 57.4.1 Mechanism of Action 57.4.2 Pharmacokinetics 57.4.3 Spectrum of Activity 57.4.4 Therapeutic Uses 57.4.5 Adverse Effects 57.5 Echinocandins 57.5.1 Mechanism of Action 57.5.2 Pharmacokinetics 57.5.3 Spectrum of Activity 57.5.4 Therapeutic Uses 57.5.4.1 Caspofungin 57.5.4.2 Micafungin 57.5.4.3 Anidulafungin 57.5.5 Adverse Effects 57.6 Griseofulvin 57.6.1 Mechanism of Action 57.6.2 Pharmacokinetics 57.6.3 Spectrum of Activity 57.6.4 Therapeutic Uses 57.6.5 Adverse Effects 57.7 Terbinafine 57.7.1 Mechanism of Action 57.7.2 Pharmacokinetics 57.7.3 Spectrum of Activity 57.7.4 Therapeutic Uses 57.7.5 Adverse Effects 57.8 Topical Antifungals 57.8.1 Topical Azoles 57.8.1.1 Ketoconazole 57.8.1.2 Clotrimazole 57.8.1.3 Miconazole 57.8.2 Topical Allylamines 57.8.3 Miscellaneous 57.8.3.1 Nystatin 57.8.3.2 Haloprogin 57.8.3.3 Tolnaftate 57.8.3.4 Undecylenic Acid 57.8.3.5 Ciclopirox Olamine 57.8.3.6 Tavaborole 57.8.3.7 Benzoic and Salicylic Acids 57.9 Conclusion Bibliography 58: Antiviral Drugs 58.1 Anti-Influenza Drugs 58.1.1 Introduction 58.1.2 Structure of Influenza Virus (Fig. 58.1) 58.1.3 Anti-Influenza Drug Classification 58.1.4 Viral RNA Replication and its Inhibitors (Fig. 58.2) 58.1.5 Prophylaxis for INFLUENZA INFECTION 58.1.6 M2 Protein Inhibitors (Adamantanes) 58.1.7 Neuraminidase Inhibitors 58.1.7.1 Oseltamivir 58.1.7.2 Zanamivir 58.1.7.3 Peramivir 58.1.7.4 Laninamivir Octanoate 58.1.8 Newer Drugs 58.2 Anti-Herpetic Drugs 58.2.1 Introduction 58.2.2 Steps of Viral DNA Replication and its Inhibitors (Fig. 58.3) 58.2.3 Classification of Anti-Herpetic Drugs 58.2.4 Attachment Inhibitor 58.2.5 Entry Inhibitor 58.2.6 DNAP α and Thymidine Kinase Inhibitors 58.2.7 DNAP delta, epsi Inhibitor 58.2.8 Newer Drugs 58.2.9 Therapeutics 58.3 Anti-Retroviral Drugs 58.3.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Box 58.1 Nucleic Acid Analogues 58.3.1.1 Salient Features 58.3.2 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 58.3.3 HIV Protease Inhibitors 58.3.4 Fusion/Entry Inhibitors 58.3.5 Integrase Inhibitors (IIs) or Integrase Strand Transfer Inhibitors (INSTIs) 58.3.6 Therapeutic Guidelines (Based on NACO Guidelines, October 2018) 58.3.6.1 HIV and TB 58.3.6.2 HIV in Pregnancy 58.3.6.3 Post-Exposure Prophylaxis 58.3.7 HIV Vaccines 58.4 Anti-Hepatitis Drugs 58.4.1 Introduction 58.4.2 Currently Available Therapies 58.4.3 Genotypes in Viral Hepatitis 58.4.4 Structure and Pathogenesis 58.4.5 Initiation of Therapy in HBV (Table 58.4) 58.4.6 Classification of Drugs Used in Hepatitis 58.4.7 Anti-Hepatitis-B Drugs 58.4.7.1 Interferonα 58.4.7.2 Lamivudine 58.4.7.3 Adefovir Dipivoxil 58.4.7.4 Entecavir 58.4.7.5 Telbivudine 58.4.7.6 Tenofovir 58.4.8 Stoppage of Therapy 58.4.9 Clinical Implication 58.4.10 Anti-Hepatitis C Drugs 58.4.10.1 Ribavirin 58.4.10.2 Directly Acting Antiviral Agents (DAAs) for Hepatitis C NS3/4A Protease Inhibitors NS5B Nucleoside and Non-Nucleoside Polymerase Inhibitors NS5A Inhibitors 58.4.10.3 Therapeutic Aspects Bibliography 59: Miscellaneous Antimicrobial Agents 59.1 Introduction 59.2 Glycopeptide Antibiotics 59.2.1 Vancomycin 59.2.2 Teicoplanin 59.2.3 Other Glycopeptide Drugs 59.3 Polypeptide Antibiotics 59.3.1 Polymyxin B and Colistin (Polymyxin E) 59.3.2 Bacitracin 59.4 Urinary Antiseptics 59.4.1 Nitrofurantoin 59.4.2 Methenamine 59.5 Antiseptics, Disinfectants, and Sterilants 59.5.1 Alcohols 59.5.2 Aldehydes 59.5.3 Halogens 59.5.4 Phenolics 59.5.5 Oxidizing Agents 59.6 Management of Sexually Transmitted Diseases (STDs) 59.6.1 Principles of Management of STD 59.6.2 Common Presentations of STD 59.6.2.1 Anogenital Ulcer 59.6.2.2 Urethritis 59.6.2.3 Vaginitis Box 59.1 Treatment for Vaginosis During Pregnancy 59.6.2.4 Pelvic Inflammatory Disease (PID) 59.6.2.5 Genital Warts Bibliography 60: Chemotherapy of Malaria and Other Protozoal Diseases 60.1 Introduction 60.1.1 Historical Perspectives of Malaria 60.1.2 Antimalarials Therapeutic Agents Box 60.1: Antimalarial Drugs Grouped Based on Elimination Half-Life (t1/2) 60.1.2.1 Quinine 60.1.2.2 Chloroquine 60.1.2.3 Sulfadoxine-Pyrimethamine 60.1.2.4 Mefloquine 60.1.2.5 Amodiaquine 60.1.2.6 Piperaquine 60.1.2.7 Primaquine 60.1.2.8 Mepacrine 60.1.2.9 Pyronaridine 60.1.2.10 Atovaquone-Proguanil 60.1.2.11 Halofantrine 60.1.2.12 Lumefantrine 60.1.2.13 Tetracycline and Doxycycline 60.1.2.14 Clindamycin 60.1.2.15 Artemisinin 60.1.2.16 Artemisinin Derivatives 60.1.2.17 Artemisinin Combination Therapy (ACTs) 60.1.2.18 Tafenoquine 60.1.3 Chemotherapeutic Regimens of Uncomplicated P. falciparum Malaria Box 60.2: Therapeutic Regimens for Uncomplicated P. falciparum Malaria in Nonpregnant Adults and Children 60.1.4 Antimalarial Regimen for Severe Malaria Box 60.3: Therapeutic Regimens for Severe Malaria 60.1.5 Other Therapeutic Regimens for Uncomplicated Malaria 60.1.6 Chemoprevention of Malaria Among High-Risk Group in Endemic Areas and Seasonal Prevention of Malaria 60.1.6.1 Chemoprophylaxis Among Travelers 60.1.6.2 Chemoprophylaxis in Pregnant and Children Travelers 60.1.6.3 Standby Emergency Treatment (SBET) 60.1.7 Antimalarial Therapeutics: Future Perspectives 60.1.7.1 Artemisinin and Partner Drug Resistance 60.1.7.2 Mass Drug Administration to Control Vector Transmission of Malaria 60.1.7.3 Malaria Vaccine 60.1.7.4 Investigational Drugs in Clinical Development 60.2 Babesiosis 60.3 Trypanosomiasis 60.3.1 Human African Trypanosomiasis (HAT) (Sleeping Sickness) 60.3.1.1 Pentamidine 60.3.1.2 Eflornithine 60.3.1.3 Nifurtimox-eflornithine combination therapy (NECT) 60.3.1.4 Suramin 60.3.1.5 Melarsoprol 60.3.2 American Trypanosomiasis (Chagas Disease) 60.4 Leishmaniasis 60.4.1 Amphotericin B 60.4.2 Pentavalent Antimonials 60.4.3 Miltefosine 60.4.4 Paromomycin 60.4.5 Combination of Drugs for Visceral Leishmaniasis 60.4.6 Topical Therapy for Cutaneous Leishmaniasis 60.5 Coccidiosis 60.6 Blastocystis 60.7 Amebiasis 60.7.1 Nitroimidazoles: Metronidazole 60.7.2 Thiazolides 60.7.3 Emetine and Its Derivatives 60.7.4 Chloroquine 60.7.5 Diloxanide Furoate 60.7.6 Paromomycin 60.7.7 Iodoquinol and Quiniodochlor 60.8 Giardiasis 60.8.1 Nitazoxanide 60.9 Trichomoniasis 60.10 Toxoplasmosis 60.11 Naegleria 60.12 Acanthamoeba 60.13 Dientamoeba 60.14 Balantidium References 61: Chemotherapy of Helminthiasis 61.1 Anthelminthic Drugs 61.1.1 Praziquantel 61.1.2 Triclabendazole 61.1.3 Thiabendazole 61.1.4 Mebendazole 61.1.5 Albendazole 61.1.6 Diethylcarbamazine Citrate (DEC) 61.1.7 Tribendimidine 61.1.8 Ivermectin 61.2 Helminthiasis: Presentation and Therapeutic Regimens 61.2.1 Trematodes 61.2.1.1 Schistosomiasis (Bilharsiasis) 61.2.1.2 Opisthorchiasis 61.2.1.3 Fascioliasis 61.2.1.4 Paragonimiasis 61.2.2 Cestodes 61.2.2.1 Noninvasive Infections 61.2.2.2 Tissue Infections Cysticercosis Echinococcosis 61.2.3 Nematodes 61.2.3.1 Ascariasis 61.2.3.2 Trichuriasis 61.2.3.3 Hookworm Infections 61.2.3.4 Strongyloidiasis 61.2.3.5 Enterobiasis 61.2.3.6 Soil-Transmitted Helminths (STH) 61.2.3.7 Invasive Nematode Infections Trichinosis, Toxocariasis, and Cutaneous Larva Migrans 61.2.3.8 Filariasis 61.2.3.9 Onchocerciasis 61.2.3.10 Loiasis 61.2.3.11 Dracunculiasis (Guinea-Worm Disease) Bibliography Part X: Pharmacotherapy of Neoplastic Diseases 62: General Principles of Cancer Chemotherapy 62.1 Terminologies 62.2 Cell Cycle 62.2.1 Phases of Cell Cycle 62.2.2 Clinical Importance of Phases 62.2.3 Classification of Cancer Chemotherapy Agents 62.2.4 Effect of Anticancer Agents on Cell Cycle Kinetics 62.2.4.1 Murine L1210 Leukaemia Model 62.2.4.2 Gompertzian Model 62.3 Combination Chemotherapy 62.3.1 Principles of Combining Anticancer Drugs for Combination Chemotherapy 62.4 Drug Resistance 62.4.1 Primary Resistance (Develops before Exposure to the Anticancer Agents) 62.4.2 Acquired Resistance (Develops with Exposure to Anticancer Agents) 62.4.3 Molecular Mechanisms Involved in the Development of Acquired Resistance 62.5 Toxicity 62.6 General Toxicity 62.6.1 Haematopoietic System 62.6.2 Gastrointestinal System 62.6.2.1 Nausea and Vomiting Phases of Vomiting Management of Breakthrough or Refractory Nausea and Vomiting Management of Anticipatory Nausea and Vomiting Antiemetic Agents 62.6.2.2 Mucositis Oral Mucositis Gastrointestinal Mucositis Drugs Causing Mucositis Management 62.6.2.3 Constipation Management 62.6.2.4 Diarrhoea Management 62.6.3 Nervous System Toxicity Box 62.1 Anticancer Drugs Causing Neurotoxicity 62.6.3.1 Prevention and Management 62.6.4 Metabolic Abnormalities 62.6.4.1 Drugs Causing Metabolic Abnormalities 62.6.4.2 Management 62.6.5 Hepatic Toxicity 62.6.5.1 Drugs Causing Hepatotoxicity 62.6.5.2 Management 62.6.6 Cardiac Toxicity 62.6.6.1 Prevention and Management 62.6.7 Renal Toxicity 62.6.7.1 Drugs Causing Renal Toxicity 62.6.7.2 Prevention and Management 62.6.8 Bladder and Urinary Toxicity 62.6.8.1 Drugs Causing Bladder and Urinary Tract Toxicity 62.6.8.2 Prevention and Management 62.6.9 Pulmonary Toxicity Box 62.2 Drugs Causing Pulmonary Toxicity 62.6.9.1 Management 62.6.10 Reproductive System 62.6.10.1 Drugs Causing Infertility 62.6.10.2 Prevention and Management 62.6.11 Carcinogenicity 62.6.11.1 Drugs Causing Secondary Cancers 62.6.12 Dermatological Toxicity 62.6.12.1 Chemotherapy-Induced Alopecia Box 62.3 Anticancer Drugs Causing Alopecia Prevention and Management 62.6.12.2 Hyperpigmentation and Nail Changes Drugs Causing Hyperpigmentation and Nail Changes 62.6.12.3 Hand-Foot Syndrome [Palmar-Plantar Erythrodysaesthesia (PPE)] Drugs Causing Hand-Foot Syndrome Prevention and Management 62.6.13 Ocular Toxicity 62.6.13.1 Drugs Causing Ocular Toxicity 62.6.13.2 Prevention and Management 62.6.14 Ototoxicity 62.6.14.1 Drugs Causing Hearing Loss 62.6.14.2 Prevention and Management 62.7 Toxicity Amelioration (Table 62.11) Bibliography 63: Cytotoxic Drugs 63.1 Introduction 63.2 Classification and Mechanism of Action 63.2.1 Alkylating Agents Box 63.1 Classification of Alkylating Agents 63.2.2 Antimetabolites Box 63.2 Classification of Antimetabolites 63.2.2.1 Mechanism of Action Folate Analogues/Antagonists Pyrimidine Analogues Cytidine Analogues Purine Analogues 63.2.3 Natural Products and Miscellaneous Drugs Box 63.3 Classification of Natural Products and Miscellaneous Drugs 63.2.3.1 Mechanism of Action Microtubule-Damaging Agents Camptothecin Analogues Epipodophyllotoxins Anticancer Antibiotics Miscellaneous 63.3 Indications and Pharmacokinetics 63.4 Adverse Drug Reactions (ADRs) Bibliography 64: Targeted Chemotherapy 64.1 Drugs Targeting the Growth Receptors and Downstream Signalling 64.1.1 EGFR Inhibitors 64.1.1.1 Drugs that Block the Receptor (Box 64.1) Box 64.1 Monoclonal Antibodies that Block the EGFR Receptor 64.1.1.2 Protein Tyrosine Kinase Inhibitors of EGFR Box 64.2 Tyrosine Kinase Inhibitors of EGFR 64.1.1.3 Osimertinib 64.1.2 HER2/Neu Inhibitors Box 64.3 Drugs that Block the Activation of Her2/Neu or Tyrosine Kinase Activation 64.1.2.1 Important Note of Adverse Drug Reactions 64.1.3 Monoclonal Antibody to the PDGFR (Platelet-Derived Growth Factor Receptor) 64.1.3.1 Olaratumab 64.1.4 Hedgehog Pathway Inhibitors 64.2 Drugs that Inhibit Intracellular Kinases 64.2.1 Inhibitors of RAF Kinase Box 64.4 RAF Kinase Inhibitors 64.2.2 Inhibitors of MEK Box 64.5 MEK Inhibitors 64.2.2.1 Other MEK Inhibitors in Development 64.2.3 Jak-Stat Inhibitors 64.2.4 BCR-ABL Inhibitors Box 64.6 BCR-ABL Inhibitors 64.3 Drugs that Inhibit Tumor Angiogenesis 64.3.1 Inhibitors of the VEGF and VEGF Pathway Box 64.7 VEGF and VEGF Pathway Inhibitors 64.3.2 VEGFR Kinase Inhibitors 64.4 Drugs that Alter the Immune Function (Box 64.8) Box 64.8 Drugs Modulating the Immune Function 64.5 Drugs Acting on Miscellaneous Targets (Box 64.9) Box 64.9 Drugs with Other Targets Bibliography 65: Hormonal Agents in the Pharmacotherapy of Cancer 65.1 Historical Timeline 65.2 Hormonal Management of Breast Cancer 65.2.1 Selective Estrogen Receptor Modulators (SERMs) 65.2.2 Aromatase Inhibitors 65.2.3 Indications for Hormone Therapy in Breast Cancer 65.3 Hormonal Management of Prostate Cancer 65.3.1 Androgen Deprivation Therapy 65.3.2 Gonadotropin-Releasing Hormone (GnRH) Agonists 65.3.3 GnRH Antagonists 65.3.4 Combined Androgen Blockade 65.3.5 Intermittent Androgen Deprivation Therapy 65.4 Resistance to Hormonal Therapy Bibliography Part XI: Miscellaneous Topics 66: Immunopharmacology 66.1 Immunosuppressants 66.1.1 Adrenocortical Steroids: Glucocorticoids 66.1.2 Calcineurin Inhibitors: Cyclosporine and Tacrolimus (FK506) 66.1.3 Cytotoxic Agents: Azathioprine, Mycophenolate Mofetil, Cyclophosphamide, and Methotrexate 66.1.3.1 Azathioprine 66.1.3.2 Mycophenolate Mofetil (MMF) 66.1.3.3 Fingolimod (FTY720) 66.1.4 Antibodies 66.1.4.1 Polyclonal Antibodies 66.1.4.2 Monoclonal Antibodies Anti-CD3 Monoclonal Antibodies Anti-IL-2 Receptor (Anti-CD 25) Antibodies: Daclizumab and Basiliximab Anti-CD 52 Monoclonal Antibody: Alemtuzumab Anti-TNF Agents: Infliximab, Adalimumab, and Etanercept Interleukin 1 Receptor Antagonist: Anakinra, Canakinumab, and Rilonacept Lymphocyte Function Associated Antigen-1 [LFA-1] Inhibition: Efalizumab and Alefacept 66.1.5 mTOR Inhibitors: Sirolimus and Everolimus 66.1.5.1 Sirolimus (Rapamycin) 66.1.5.2 Everolimus 66.2 Tolerogens 66.2.1 Co-Stimulation Blockade 66.2.2 Donor Cell Chimerism 66.2.3 Soluble HLA 66.2.4 Antigens 66.3 Immunostimulants 66.3.1 Levamisole 66.3.2 Thalidomide 66.3.3 Lenalidomide 66.3.4 Bacillus Calmette Guerin (BCG) 66.3.5 Recombinant Cytokines: Interferons and Interleukins 66.3.5.1 Interferons 66.3.5.2 Aldesleukin Bibliography 67: Dermatological Pharmacology 67.1 Introduction 67.1.1 Dermal Pharmacokinetics 67.1.2 Vehicles and Dermatological Formulations 67.2 Selective Topical Preparations 67.2.1 Melanizing and Demelanizing Agents 67.2.2 Sunscreens 67.2.3 Antihistamines or Antipruritic Agents 67.2.4 Photochemotherapy 67.2.5 Topical Steroids Box 67.1 Topical Corticosteroid Formulations Available and Classified Based on Potency Box 67.2 Skin Disorders Ranked in Order of Sensitivity and Responsiveness to Steroids 67.2.6 Keratolytics 67.2.7 Retinoids Box 67.3 Topical and Systemic Retinoids and their Clinical Uses 67.3 Drugs for Psoriasis Box 67.4 Biological Agents for Psoriasis 67.4 Topical Anti-Infective Agents 67.4.1 Topical Antibacterial Agents 67.4.1.1 Mupirocin 67.4.1.2 Retapamulin 67.4.1.3 Bacitracin, Neomycin, and Polymyxin B 67.4.1.4 Gentamicin 67.4.1.5 Silver Sulfadiazine 67.4.1.6 Mafenide 67.4.2 Management of Common Bacterial Skin Infections 67.4.2.1 Drugs for Acne Vulgaris 67.4.2.2 Impetigo 67.4.2.3 Furuncle or Boil 67.4.3 Topical Antiviral Agents 67.4.3.1 Acyclovir 67.4.4 Management of Common Viral Skin Infections 67.4.5 Topical Antifungal Agents Box 67.5 Topical Antifungals and FDA Approved Indications 67.4.6 Topical Agents for Infestations Box 67.6 Topical Agents for Parasitic Infestations, their Target Parasites, and the Mechanism of Action 67.4.7 Drugs Affecting Hair Growth (Treatment of Androgenic Alopecia) 67.4.7.1 Minoxidil 67.4.7.2 Finasteride 67.4.7.3 Spironolactone 67.4.8 Miscellaneous Cytotoxic, Immunosuppressant, and Immunomodulatory Agents in Skin Disorders Bibliography 68: Ocular Pharmacology 68.1 Pharmacokinetic Considerations 68.1.1 Drug Formulation 68.1.2 Absorption into the Eye 68.1.3 Distribution 68.1.4 Metabolism 68.2 Chemotherapeutic Drugs in the Eye 68.2.1 Bacterial Infections (Box 68.1) Box 68.1 Antibiotics Used in Bacterial Infections and Various Infective Conditions of the Eye 68.2.2 Viral Infections (Box 68.2) Box 68.2 Antivirals Used in Viral Infective Conditions of the Eye 68.2.3 Fungal Infections (Box 68.3) Box 68.3 Antifungals Used in Fungal Infective Conditions of the Eye 68.2.4 Protozoal Infections 68.3 Drugs Used in Glaucoma 68.4 Anti-Inflammatory and Immunomodulatory Drugs (Table 68.2) 68.5 Antihistamines and Mast Cell Stabilizers Used in Allergic Conditions 68.6 Ocular Toxicity of Systemic Agents (Table 68.3) Bibliography 69: Nutritional Supplements and Herbal Medicines 69.1 Introduction 69.1.1 Differences from Pharmacotherapy 69.2 Regulations 69.2.1 FSSAI Regulations 69.2.2 Important Take-Away from the Guidelines 69.2.3 Manufacturing Regulations 69.3 Usage 69.4 Concerns Over Nutraceuticals Bibliography 70: Immunoglobulins and Vaccines 70.1 Immunity 70.2 Vaccines and Types 70.2.1 Live Attenuated Vaccines (LAVs) 70.2.2 Toxoid 70.2.3 Killed/Inactivated Vaccine 70.2.4 Subunit Vaccine 70.3 Immunization Programme in India 70.4 Immunization in Pregnancy Box 70.1 Inactivated and Live Attenuated Vaccines Approved to be Used in Pregnancy Box 70.2 Vaccine Recommendations in Pregnancy 70.4.1 Tetanus Toxoid Vaccines 70.4.2 Inactivated Influenza Vaccine 70.4.3 Meningococcal Vaccine 70.4.4 Rubella Mono Vaccines and Combined Vaccines 70.4.5 Human Papilloma Virus (HPV) Vaccine 70.4.6 Yellow Fever Vaccine 70.5 Immunization for Travellers 70.6 Vaccines for Chronic Non-Communicable Diseases 70.6.1 Cancer Vaccines 70.6.2 Vaccines for Atherosclerosis Box 70.3 Summary of Different Vaccine Targets Bibliography