The primary objective of this 4-volume book series is to educate PharmD students on the subject of medicinal chemistry. The book set serves as a reference guide to pharmacists on aspects of the chemical basis of drug action. Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems is the third volume of the series. This volume features 8 chapters focusing on a comprehensive account of drugs affecting both the cardiovascular system and the endocrine functions. The volume informs readers about the medicinal chemistry of relevant drugs, which includes the mechanism of drug action, detailed structure-activity relationships and metabolism. Topics covered include drugs that affect the renin-angiotensin system, calcium channel blockers, diuretics, hematological agents (anticoagulants, thrombolytic and antiplatelet agents), antidiabetics, antihistamines, proton pump inhibitors and therapeutic hormones. Each chapter also offers case studies and self-assessments to facilitate discussion and learning. The book equips students with a scientific foundation to competently evaluate, recommend and counsel patients and health care professionals regarding the safe, appropriate, and cost-effective use of medications. Students and teachers will also be able to integrate the knowledge presented in the book and apply medicinal chemistry concepts to understand the pharmacodynamics and pharmacokinetics of therapeutic agents in the body. The information offered by the book chapters will give readers a strong neuropharmacology knowledge base required for a practicing pharmacist.
Readership
PharmD / pharmacology students and teachers.Table of Contents
Chapter 1 Drugs Affecting Renin-Angiotensin System- M. O. Faruk Khan and Karrie Murphy
- Historical Background
- Introductory Concepts
- The Renin-Angiotensin System (Ras)
- Angiotensin-Converting Enzyme Inhibitors (Aceis)
- Structure of Ace Active Site and Mechanism of Ang I Hydrolysis
- Inhibition of Ace - the Acei-Ace Interaction
- Pharmacophore and Sar Summary of Aceis
- Sar Summary
- The Individual Aceis and Their Structural and Therapeutic Evaluations
- Sulfhydryl-Containing Inhibitor - Captopril
- Dicarboxylate Containing Inhibitors
- Phosphinate Containing Inhibitor - Fosinopril
- Angiotensin Ii Receptor Blockers (Arbs)
- The At1R Binding Pockets
- Pharmacophore of Arbs and Structure-Activity Relationship
- Sar Summary
- The Individual Arbs and Their Structural and Therapeutic Evaluations
- Recalls of the Arbs
- Therapeutic Considerations of Acei and Arbs
- Renin Inhibitor Aliskiren (Tekturna® )
- Case Study
- Drug Discovery Case Studies
- Discovery of Aceis
- Teprotide-The First Clue
- Carboxypeptidase a - the Homology Model
- Development of Captopril
- Development of Enalapril and Lisinopril
- Development of Arbs
- From Saralasin to Losartan and Eprosartan
- Student Self-Study Guide
- Student Self-Assessment Questions
- References
- Taufiq Rahman and M. O. Faruk Khan
- Historical Backgrounds of Ca 2+ - Channel Blockers
- Introductory Concepts
- The Voltage Gated Ca 2+ - Channels (Vgccs) and Their Clinical Significance
- Sub-Classes of Vgcc
- Calcium Channel Blockers
- The 1,4-Dihydropyridines (Dhps)
- Structure Activity Relationship (Sar) of Dhp Derivatives
- No-Releasing Activity of 1,4-Dihydropyridines
- Individual 1,4-Dihydropyridine Drugs
- Phenylalkylamines (Paas)
- Structure-Activity Relationship of the Phenylalkylamines
- Verapamil
- Benzothiazepines (Btzs)
- Structure-Activity Relationships of Benzothiazepines
- Diltiazem
- Diaminopropanol Ethers
- Clinical Case Studies
- Case
- Case
- Case
- Drug Discovery Case Studies
- Discovery of Verapamil
- Discovery of Nifedipine and Its Analogues
- Student Self-Study Guide
- Student Self-Study Questions
- Questions 6 - 8 Are Based on the Following Structures:
- References
- David J. Weldon, Krista G. Brooks and M. O. Faruk Khan
- Historical Perspectives
- Introductory Concepts
- Osmotic Diuretics
- Mechanism of Action of the Osmotic Diuretics
- Available Therapeutic Agents (Table 2)
- Carbonic Anhydrase Inhibitors
- Mechanism of Action of Cais
- Sar Summary of Sulfonamides as Cais
- Available Therapeutic Agents (Tables 3 and 4)
- Thiazide Diuretics
- Mechanism of Action of Thiazide Diuretics
- Sar Summary of Thiazide Diuretics
- Available Therapeutic Agents (Table 5)
- Loop Diuretics
- Mechanism of Action of Loop Diuretics
- Sar Summary of Loop Diuretics
- Available Therapeutic Agents
- Potassium-Sparing Diuretics
- Aldosterone Antagonists
- Available Agents
- Non-Steroidal Mra: Finerenone (Kerendia®)
- Epithelial Sodium Channel (Enac) Antagonists
- Available Agents (Table 8)
- Case Studies
- Drug Discovery Case Stories
- Discovery of Carbonic Anhydrase Inhibitor: Acetazolamide
- Discovery of the Thiazide Diuretic Chlorothiazide
- Discovery of Loop Diuretic Furosemide
- Student Self-Study Guide
- Student Self-Assessment Questions
- References
- C Hapter 4 Anticoagulants, Antiplatelets and Thrombolytic Agents
- M. O. Faruk Khan and A. R. M. Ruhul Amin
- Historical Background
- Introductory Concepts
- Hemostasis
- Biochemical Pathway of Clotting
- Blood Coagulation Risk Factors
- Anticoagulants
- Heparin and Derivatives
- Ufhs and Lmwhs
- Mechanism of Action
- Adverse Effects, Contraindications, Antidotes and Pharmacokinetics
- Fondaparinux (Arixtra®)
- Warfarin
- Chemistry, Mechanism of Action, and Therapeutic Uses
- Pharmacokinetics
- Monitoring of Warfarin Therapy
- Food and Drug Interactions
- Direct Thrombin Inhibitors (Dtis)
- Hirudin and Its Recombinant Derivatives
- Argatroban
- Oral Direct Thrombin Inhibitor: Dabigatran
- Direct Factor Xa Inhibitors
- Rivaroxaban (Xarelto®)
- Apixaban (Eliquis®)
- Edoxaban (Savaysa®)
- Betrixaban (Bevyxxa®)
- Antiplatelet Agents
- Cyclooxygenase Inhibitor: Aspirin
- Glycoprotein Iib/Iiia Receptor Blockers
- Abciximab (Reopro®)
- Eptifibatide (Integrilin®)
- Tirofiban (Aggrastat®)
- P2Y12 Receptor Blockers: Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor
- Thienopyridine Derivatives
- Adp Analog: Cangrelor (Kengreal®)
- Cyclopentyltriazolopyrimidine: Ticagrelor
- Phosphodiesterase (Pde) Inhibitors
- Dipyridamole
- Cilostazol (Pletal®)
- Anagrelide (Xagrid®)
- Protease Activated Receptor 1 (Par-1) Antagonist
- Vorapaxar (Zontivity®)
- Thrombolytics
- Streptokinase
- Alteplase
- Reteplase (Retavase®)
- Tenecteplase (Tnkase®; Metalyse®; Elaxim®)
- Defibrotide (Defitelio®)
- Antidotes of Anticoagulants and Antiplatelets
- Protamine
- Andexanet Alfa (Andexxa®)
- Idarucizumab (Praxbind®)
- Vitamin K
- Platelet Stimulating Agents
- Thrombopoietin Receptor Agonists
- Eltrombopag (Promacta®)
- Romiplostim (Nplate®)
- Antifibrinolytic Agents
- Tranexamic Acid
- Ε-Aminocaproic Acid (Amicar®)
- Clinical Case Study
- Drug Discovery Case Study
- Discovery of Warfarin
- Discovery of Ticagrelor
- Discovery of Apixaban
- Student Self-Study Guide
- Student Self-Assessment Questions
- Match the Drug Structures (A-H) With the Appropriate Names (20-26).
- References
- C Hapter 5 Antihistamines, Proton Pump Inhibitors and Related Drugs
- M. O. Faruk Khan
- Historical Background
- Introductory Concepts
- Histamine Receptors
- Histamine Structural Considerations
- Histamine Agonists
- Receptor Structures and Pharmacophore Models of the H1 and H2 Receptors
- The Histamine H1 Receptor
- The Histamine H2 Receptor
- Histamine H1 Antagonists
- General Mechanism of Antihistaminic Action
- General Structure and Classification of Antihistamines
- Therapeutic Evaluations of Each Class of Antihistamines
- The General Structure Activity Relationship (Sar)
- The Aminoalkanes and Aminoalkenes (Propylamines)
- The Piperazines or Cyclizines
- The Piperidines
- The Aminoalkyl Ethers - Ethanolamines and Propanolamines
- Ethylenediamines
- Phenothiazines
- Miscellaneous Antihistamines
Author
- M. O. Faruk Khan
