Computer-Aided Drug Design and Delivery Systems

Transcription

1 Computer-Aided Drug Design and Delivery Systems Ahindra Nag Baishakhi Dey Me Graw New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto

2 Preface 1 Computer-Aided Drug Design (CADD) Introduction Rational Drug Design Factors Contributing to Drug Discovery Drug Design with the Help of Software Drug Discovery Process How Computers Help in Drug Design Computer Simulation for Drug Design Drug Design Theory Role of Computers in Drug Design: Their Success and Failure Rational Drug Design Software Scanners Builders Hybrids RACHEL Software Package RACHEL Component Specification Language 14 References 16 2 Drug Delivery Systems Introduction Development of Sustained-Release Drug Delivery Systems Delayed-Release Systems Advantages of Sustained Drug Delivery Systems Important Physicochemical Properties of the Drug Aqueous Solubility and pk a Partition Coefficient " Drug Stability Protein Binding Biologic Properties Absorption Distribution Metabolism Elimination and Biologic Half-Life Xlll vii

3 2.5 Safety Considerations Transdermal Delivery Systems Membrane-Moderated Systems Adhesive Diffusion-Controlled Systems Matrix Dispersion-Type Systems Microreservoir Systems Targeted Delivery Systems Nanoparticles Liposomes Resealed Erythrocytes Transdermal Delivery Systems Basic Components of Transdermal Devices Choice of Drug Excipients Adhesive and Packaging Pressure-Sensitive Adhesives Peel Adhesion Properties Tack Properties Shear Strength Properties Transdermal Devices Membrane-Moderated Devices (Reservoir Devices) Adhesive Diffusion-Type Devices (Mixed Monolithic Reservoir Devices) Matrix Dispersion-Controlled Device (Monolithic Device) Microreservoir-Type Devices Microreservoir Dissolution-Controlled Devices In Vitro Release Kinetics In Vitro Skin-Permeation Kinetics IV-IV Correlation Optimization of Transdermal Systems Skin Irritation Sensitization 37 References 37 3 Bioinformatics of Drug Molecules and Databases Introduction The Concepts, Goals, and Aims of Bioinformatics Fields of Bioinformatics: Role and Relevance in Biotechnology 40

4 jx 3.4 Proteomics: Protein Sequence Databases Data Retrieval Systems System Retrieval Systems Applications of Bioinformatics Bioinformatics in Rational Drug Design and the Medical Sciences Bioinformatics and Chemical Engineering Brief Introduction to Bioinformatics Databases Microarray Database Bioinformatics Scenario 52 References 54 4 Lipase- and Esterase-Mediated Drugs and Drug Intermediates Introduction Lipase Used in Biotransformations Solvents for Biocatalysis Sources of Lipase Location of Action Structure of Lipase Mechanism of Action Production of Lipase Statistical Design Approach for Optimization of Process Parameters and Nutritional Requirement for Lipase Production Immobilization Role of Lipases in the Preparation of Drugs and Drug Intermediates Esterase as Hydrolase Enzyme Esterase Production Preparation of Drugs and Drug Intermediates by Esterases 79 References 87 5 Pharmacokinetics and Pharmacodynamics in Drugs Introduction Pharmacokinetic Parameters Pharmacodynamic Parameters Absorption of Drugs Factors Affecting Drug Absorption Mechanism of Drug Absorption... 93

5 5.4.3 Factors Influencing Drug Absorption Manufacturing Variables Distribution of Drugs Factors Affecting Drug Distribution Factors Affecting Differences in the Distribution of Drugs Plasma Protein Binding Physiologic Barriers Bio transformation/ Metabolism Excretion of Drugs Pharmacokinetic Equations Pharmacodynamics Factors Influencing Drug Action How Does a Drug Act? 132 References Biomarkers, Biosensors, and Robotics in Medicine Introduction Developmental History of Biomarkers Different Types of Biomarkers Use of Biomarkers in Cancer Biomarkers in Medical Science Recent Advances in Biomarkers Disadvantages of Biomarkers Biosensors Developmental History of Biosensors General Instrumentation and Operation of a Biosensor Biosensors in Drug Design Biosensors in Biomedical Research Robotics in Surgery Background and History of Surgical Robots Robot-Assisted Surgery Advantages and Disadvantages of Robot-Assisted Surgery Applications of Robotic Surgery Practical Uses of Surgical Robots Today Future of Robotic Surgery Conclusion 166 References 167

6 xi Biomedical Instrumentation Introduction Biomedical Instrumentation Measurements Instrumentation for Cardiovascular Measurements Measurement of Blood Flow and Cardiac Output Measurement of Heart Sounds Instrumentation for Measurements of the Nervous System Electromyographic Measurements Instrumentation for Psychophysiologic Measurements Instrumentation for the Experimental Analysis of Behavior Respiratory Therapy Equipment Pacemakers and Defibrillators Instrumentation for the Medical Use of Radioisotopes Ophthalmic and ENT Instruments Ultrasonography Computed Tomographic Scanning (CT Scanning) Positron-Emission Tomographic (PET) Scanning Magnetic Resonance Imaging 197 References 198 Index 201