General and Molecular Pharmacology: Principles of Drug Action

With a focus on functional relationships between drugs and theirtargets, this book covers basic and general pharmacology, from acellular and molecular perspective, with particular attention to the mechanisms of drug action the fundamental basis forproper clinical use– without neglecting clinical application,toxicology and pharmacokinetics.     Covers cell and molecular pharmacology,bringing together current research on regulation of drug targets,at a level appropriate for advanced undergrad and graduatestudents     Discusses the relevance ofpharmacokinetics and drug development for the clinical applicationof drugs     Presents material from the perspective ofdrug targets and interaction, the theoretical basis of drug actionanalysis, and drug properties     Focuses on structure–functionrelationships of drug targets informing about theirbiochemical and physiologic functions and experimental and clinicalpathways for drug discovery and development     Has a companion website that offers ahost of resources: short additional chapters about methodology,topics at the forefront of research, all figures and tables fromthe book, and Power Point slides INDICE: SECTION 1–INTRODUCTION TO PHARMACOLOGY.1 Essential lexicon of pharmacologyF. Clementi and G. Fumagallli.The social impact of pharmacology.Essential lexicon.1.1 Alternative or non–conventional therapies.1.2 The placebo.2 A short history of pharmacologyV. Sironi.Birth and historical developments of pharmacology.Modern pharmacology.The biotechnology era and the pharmacology in the third millennium.2.1 The drugs of the ancients.2.2 Ehrlich s chemotherapy: receptor theory and clinical experimentation.2.3 The thalidomide case.SECTION 2 GETTING THE DRUG TO ITS SITE OF ACTION.3 Cellular basis of pharmacokineticsR. Fesce and G. Fumagalli.A quick journey with a drug in the body.Crossing cell membranes.Drug diffusion across membranes and the Fick s law.Drug diffusion to organs and tissues.Properties of the most important cell barriers.3.1 Pharmacokinetics.4 Drug absorption and administration routesR. Fesc and, G. Fumagalli.General rules about drug absorption rate.Enteral routes of administration.Systemic parenteral routes of administration.Other routes of drug administration.Absorption kinetics.Drug delivery: formulations to control absorption and release site.5 Drug distribution and eliminationR. Fesce and G. Fumagalli.Distribution.Elimination.Renal excretion of drugs.Hepatic excretion and entero–hepatic cycle.6 Drug metabolismE. Chiesara, L. Marabini and S.Radice.Metabolic modification of drug activity.Two phases of drug metabolism.Phase I reactions.Phase II enzymatic reaction.Extrahepatic biotransformations.Pharmaco–metabolic induction and inhibition.6.1 Factors that modify drug metabolism.6.2 Induction of drug metabolism.6.3 Modulations of efficacy due to interactions between synthetic and herbal drugs.7 Control of drug plasma concentrationR. Fesce and G. Fumagalli.Time course of plasma drug concentration following a single administration.Drugs distribute to organs and tissues and then are eliminated.Drug plasma concentration time course during ripetitive administration.Multi compartmental kinetics.Corrections of the therapeutic regimen.7.1 Therapeutic drug monitoring.7.2 The distribution of drugs administered by inhalation.SECTION 3 RECEPTORS AND SIGNAL TRANSDUCTION.8 Drug–receptor interactions: quantitative and qualitative aspectsG. Rovati and V. Capra.General properties of drug receptors.Chraracteristics of drug–receptor interactions.Quantitative aspects of drug effects: dose–response curves.From drug–receptor interaction to drug response.8.1 Methods for receptor investigations.8.2 Receptor binding assays.9 Receptors and modulation of their responseF. Clementi and G. Fumagalli.Classes of receptor and  strategies of signal transduction.Control of receptor localisation in the cell membrane.Intracellular traffic of cell receptors.Modulation of receptor responses.Receptor modulation by drugs.9.1 Birth and evolution of receptor s theories.9.2 Regulation of the receptor response.9.3 Intracellular trafficking of receptors.10 Adaptation to drug response and drug dependenceC. Chiamulera.Molecular, cellular and systemic adaptation.Drug addiction as a paradigm of allostatic adaptation.Therapy for drug dependence.10.1 Types of memory.10.2 A modern definition of memory.10.3 Conditioning as the core od addictive behavior.10.4 Visualization techniques.11 Pharmacological modulation of post–translational modificationsM. Di Luca, F. Valtorta and F. Gardoni.Protein phosphorilation.SUMOylation.Ubiquitination.Glycosylation.Acetylation.Hydroxylation.Carboxylation.Methylation.S–nitrosylation.Disulfide bonds.Lipids modifications.Pharmacological control of post–translational modifications.12 Calcium homeostasis within the cellsJ. Meldolesi and G.Fumagalli.The cytosol, a crossroad of Ca2+ fluxes.The plasma membrane: channels, pumps and transporters.Ca2+ in the intracellular organelles.Ca2+ in cell pathology.12.1 Cytosolic proteins that bind Ca2+ with high affinity.12.2 Surface Ca2+ channels: TRP, ORAI, SOCC channels and their functions.12.3 Ca2+ pumps of plasma membrane and intracellular rapidly exchanging Ca2+ stores.12.4 Ca2+ binding proteins of the ER lumen.12.5 ER channels: Ip3 and Ryanodine receptors.12.6 Local Ca2+ spikes can evolve into oscillations and waves.12.7 Mitochondria: semiautonomous organelles that need ER to operate.12.8 The nucleus is also operative in  Ca2+ homeostasis.13 Pharmacology of MAP KinasesL. Vicentini and M. G. Cattaneo.The MAPK family and the activation mechanism.MAPK specificity.Pharmacological inhibition of MAPK.13.1 Phosphatases with dual specificity as regulators of MAPK activity.13.2 Role of MAPKs in memory and learning.13.3 ERK activation by G protein–coupled receptors.14 Small G ProteinsE. Ligeti and T. Wieland.Structure and funtion of SMGs.Physiological role of major SGG families.Posttranslational modifications and subcellular localizationsì of SMGs.Regulatory proteins.Modulation of small G–protein signaling by bacterial toxins and drugs.Future perspectives.15 Integration in intracellular transduction of receptor signalsJacopo Meldolesi.Dualism of receptors in the nucleus and in the cytoplasm.Heterogeneity of receptor assembly.Transduction cascades depend on cross–talk and complementarity among receptors.Development of new drugs and therapies.15.1 Neurotrophins.15.2 Wnt and Hedgehog signaling pathways: two future drug targets?.SECTION 4 RECEPTOR CLASSES.16 Ligand gated ion channelsC. Gotti and F. Clementi.Tissue distribution and subcellular localization of LGICs.Molecular organisation of LGICs.Topology of LGICs.Modulation of  LGICs.Cross talk with other receptor systems.Mechanisms of action of drugs that modulate LGICs.16.1 Evolution of ligand gated ion channels.16.2 How to identify the amino acids that make up the inner wall of LGICs.17 G–protein coupled receptorsL. Vallar, M.P. Abbracchio and L. Vicentini,.Molecular organisation of GPCRs.Molecular organization and function of G protein.Effectors pathways of GPCRs.Interactions of GPCRs with other proteins.17.1 Orphan receptors.17.2 Structure and conformation modifications of GPCRs.17.3 Drugs active on phosphodiesterases.18 Growth factor receptorsS. Giordano, C. Boccaccio and P. M. Comoglio.Molecular structure of growth factors receptors.Receptor activation and signal transduction.Pharmacological approaches to the control of growth factor activity.19 Cytokines receptorsM. Locati.Classification of cytokines and their receptors.Cytokines in their biological settings.Pharmacology of cytokines and of their receptors.20 Adhesion molecules receptorsG. Berton and C. Laudanna.Adhesion receptors.Signal transduction by adhesion receptors.Adhesion receptors as drug targets.20.1 Adhesion and platelets activation.20.2 Adhesion and leukocyte recruitment.21 Soluble Cytochines receptors and monoclonal antibodies in pathophysiology and therapyA. Mantovani and A. Vecchi.Soluble receptors.Monoclonal antibodies.SECTION 5 MODULATION OF GENE ESPRESSION.22 Pharmacology of transcriptionR. Benfante and D.Fornasari.Introduction to the mechanisms of transcriptional regulation.Transcriptional regulation by extracellular stimuli.From the pharmacology of transcription to pharmacoepigenomics.22.1 Pharmacoepigenomics.23 Pharmacogenetics and personalized therapyD. Fornasari.Variations of drug responses and the definition of pharmacogenetics.Genetic basis of variability in drug response.Genetic polymorphisms and drug metabolism.Genetc polymorphisms in encoding phase l enzymes.Polymorphisms in genes encoding phase II enzymes.Genetic polymorphisms in genes encoding transporters involved in drug absorption, distribution and excretion.Genetic polymorphisms in genes encoding transporters involved in drug absorption, distribution and excretion.Genetic polymorphisms in genes encoding molecular targets of drug action.Methods of pharmacogenetic studies.The future of pharmacogenetic.23.1 Genetic polymorphisms.24 Intracellular receptorsA. Maggi and E. Vegeto.Structural features of intracellular receptors.Intracellular receptors as ligand–regulated transcription factors.Extra–nuclear activity of intracellular receptors.Physiological activities and pharmacological control of intracellular receptors.24.1 Ligands of intracellular receptors.25 RNA molecule as a drug: from RNA interference to aptamersV. Fulci and G. Macino.Mechanisms of action of RNA drugs.Delivery.General chemical structure.Pharmaco–toxicology.Present use and future perspectives.SECTION 6  REGENERATIVE MEDICINE.26 Regenerative medicine and gene therapyL. Conti and E. Cattaneo.Principles of regenerative medicine.Definition, classification and features of stem cells.Stem Cells–based drugs.Cell therapy and regenerative medicine.Gene therapy.Future perspectives.26.1 History and development of iPS cell research.26.2 Use of blood stem cells in haematology.26.3 Viral vectors for gene therapy in somatic cells.26.4 Gene therapy for cystic fibrosis and tumors.SECTION 7 PHARMACOLOGICAL CONTROL OF MEMBRANE TRANSPORT.27 Ion channelsM. Taglialatel and E. Wanke.Ion channels and transporters.Characterization  and function of ion channels.Structural organization of ion channels.Drugs and ion channels.Sodium channels.Calcium channels.Potassium channels.Non selective channels, anionic channel and others.27.1 How to observe ion channel current in real time.27.2 How to study interactions between drugs and ion channels.27.3 Natural peptide toxins.27.4 Physiopathology and pharmacology of muscular contraction.27.5 Physiopathology of VGCCs: genetic studies in animal models and humans.27.6 Drug induced long QT syndrome.27.7 TRP Channels.27.8 Non–voltage dependent Na+ channels and their role as mechano–sensitive and acid–sensitive transducers.27.9 Anion channels.27.10 Water channels: Aquaporins.27.11 Voltage–independent Ca2+ channels activated by store depletion.27.12 Pharmacological modulation of gap junctions channels and electric synapses.28 Membrane transportersL. Annunziato, G. Pignataro and G. Di Renzo.Transporter classification.ATP dependent transporters.ATP independent transporters.Na/K ATPases.H/K ATPases.Plasma membranes Ca2+ ATPases.Sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA).Sodium/calcium exchanger.Sodium/ proton exchanger.Na+/K+/Cl– co–transporter (NKCC).28.1 Systems for drug extrusion.28.2 Cardiac glycosides.28.3 Diuretic drugs.28.4 The Na?/Ca 2+exchanger as a new molecular target for the development of drugs to treat cerebral ischemia.29 Neurotransmitter transportersG. Di Chiara.Neurotransmitter transporters and synaptic function.Neurotransmitter transporter families.Na+/K+ –dependent transporters for excitatory aminoacids.Na+/Cl –dependent plasma membrane transporters.H+–dependent vesicular transporters.29.1 Therapeutic properties  of GABA transporter inhibitors.29.2 Mechanism of action of amphetamines.29.3 Inhibitors of amine transporters and antidepressant drugs.SECTION 8 CONTROL OF PROTEOLYSIS.30 Intracellular proteolysisF. Di Lisa and E. Melloni.General characteristics of proteases.Characteristics and regulation of intracellular proteolysis.Lysosomal proteases.Compartmentalized proteases with specific functions.Cytoplasmic proteases.Proteasome inhibitors as anti–inflammatory and anti–tumoral drugs.Exogenous intracellular proteases.30.1 Protease classification and nomenclature.30.2 Autophagy.30.3 ACE inhibitors and their effects on cardiovascular system.30.4 Ubiquitin and proteasome.31 Extracellular proteolysisF. Blasi.The extracellular matrix proteolytic degradation systems.Plasminogen system and its activators.Matrix metalloproteases.31.1 Plasminogen activators and cardiovascular diseases.31.2 Plasminogen activators and tumor malignancy.31.3 uPAR, cancer and stem cells..SECTION 9 CONTROL OF CELL CYCLE AND CELLULAR PROLIFERATION.32 Cell cycle and cell deathM. Corazzari and M.Piacentini.Cell cycle.Cell death.Programmed cell death or apotosis.Necrosis.Drugs and apoptosis.32.1 P53: regulator of mitotic cycle progression and apoptosis inducer.32.2 Mitotic catastrophe.32.3 Intrinsic apototic pathway induced by endoplasmic reticulum.33 Mechanisms of action of antitumor drugsG. L. Beretta, L. Gatti and G.Perego.Conventional antitumor drugs.Target specific antitumor drugs.Monoclonal antibodies in clinical use.33.1 Mechanisms of drug resistance in cancer chemotherapy.SECTION 10 CONTROL OF CELLULAR METABOLISM.34 Mitochondria, oxidative stress and cell damage: Pharmacological perspectivesCl. De Palma, O. Cantoni and F. Di Lisa.Reactive Oxygen Species (ROS).The mitochondrial permeability transition pore.Drug and mitochondria.34.1 Structure, organization and dynamics of mitochondria.35 Pharmacological control of lipid synthesisL. Arnaboldi, A. Corsini and N. Ferri.Cholesterol Biosynthesis.Biosynthesis of fatty acids.Triglycerides biosynthesis.Transcriptional control of genes involved in lipid metabolism.Lipid transfer proteins.35.1 Pharmacology of the mevalovate pathway.35.2 Pharmacology of the biosynthesis of fatty acids.35.3 Pharmacology of biosynthesis of triglycerides.35.4 Role of LXR receptors in lipid metabolism and their pharmacological role.35.5 The lipoproteins.34.6 Lipid Transfer proteins.36 Glucose transport and pharmacological control of glucose metabolismP. Moghetti and G  Zoppini .Mechanisms of glycemic control.Pharmacology of glycemic control.Insulin resistance and new therapeutic perspectives.36.1 The controinsular hormones.SECTION 11 INTERCELLULAR COMUNICATION.37 Pharmacological regulation of synaptic functionM. Matteoli, E. Menna, C. Capuano and Cl. Verderio.The Synapse.Synaptic organization complexity and synaptopathies.The presynaptic compartment: Neurotransmitter release.The post–synaptic compartment: Signal reception.Synapse formation, maintenance and plasticity.The pharmacology of neurosecretion.37.1 Role of astrocytes in synaptic transmission.37.2 Dynamic organization of synaptic vesicle pools.37.3 Endocytic process of synaptic vesicles.37.4 Neupeptide secretion.37.5 Role of lipids in exo–endo cytotic cycle of synaptic vesicles.38 Catecholaminergic transmissionS  Sigala, M. Memo, M. C. Missale, M. Pizzi and P. F. Spano.The catecholaminergic system in the autonomic nervous system.The catecholaminergic system in the central nervous system.Synthesis of catecholamines.Vesicular storage anmd release of catecholamines and drugs acting on them.Catabolism and reuptake of catecholamines..Catecholamines receptors.Principles of drug actions on catecholaminergic receptors.38.1 Dopamine and Parkinson s disease.38.2 Brain reward circuits.38.3 Modulation of the functional properties of dopamine receptors by interactions with other proteins.39 Cholinergic transmissionG. Pepeu.Distribution and function of the cholinergic systems.Acetylcholine synthesis and metabolism.Acetylcholine intracellular storage and release.Cholinergic receptors.Drugs acting on cholinergic receptors.39.1 Methods for investigating the role of brain cholinergic system in learning and memory.39.2 Cholinesterases and cholinesterase inhibitors.39.3 Neuromuscular blocking agents.40 The serotonergic transmissionM. Popoli, L. Musazzi and G. Racagni.Functions and distribution and of serotonergic system in the body.Synthesis and metabolism of serotonin.Vesicular storage, release and extracellular clearance of serotonin.Classification of serotonin receptors.Drugs acting on serotonin receptors.40.1 Drugs active on the serotonergic system.40.2 Serotonergic system and modulation of pain perception.40.3 Pineal gland, melatonin, serotonin and regulation of circadian rhytms.41 Histaminergic TransmissionE. Masini and L. Lucarini.Distribution and function of histaminergic system.Synthesis and metabolism of histamine.Histamine receptors and their pharmacological modulation.41.1 Histamine receptors and signal transmission pathways.42 GABAergic TransmissionM. Serra, E. Sanna and G.Biggio.GABA distribution, synthesis and metabolism.GABA release and uptake.GABAA receptor classification.Pharmacology of GABA A receptors.42.1 Antiepileptic drugs with GABAergic mechanism of action.42.2 Physiological and pharmacological modulation of GABA A receptor gene expression.43 Glutamate mediated neurotransmissionF. Moroni.Glutamate synthesis and metabolism.Glutamate transporters and signal inactivation.Glutamate receptors.Glutamate neurotransmission in physiology and pathgology.43.1 Long–term potentiation (LTP) and long term depression (LTD) of excitatory synaptic transmission.44 Purinergic transmissionS. Ceruti, F. Cattabeni and M. P. Abbracchio.Purines as intercellular transmitters.Receptors for purine.Biological roles of purines.44.1 Purines and ischemia.44.2 Drugs active on purinergic system.45 NeuropeptidesL. Negri and R. Lattanzi.Neuropeptide synthesis.Storage and secretion of neuropeptides.Peptidergic transmission.Neuropeptide functions and therapeutic potential.45.1 Characteristics of some neuropeptides.45.2 Hypothalamus and neuropeptides.45.3 Neuropeptides and nociception.46 The opioid systemP. Romualdi and S. Candeletti.Endogenous opioid peptides.Opioid receptors.Opioid receptor distribution and effects.Tolerance and physical dependence to opiates.Addiction to opioids.46.1 Opiate drugs.46.2 Nociceptin.46.3 Opioid receptor distribution.46.4 Neurobiological basis of acute and chronic pain.46.5 OIpiate addiction.47 The endocannabinoid systemD. Parolaro and T.Rubino.Cannabinoids receptors.Endocannabinoids.Biological functions of endocannabinoids.Drugs affecting the cannabinoid system.47.1 Drugs acting on the endocannabinoid system.47.2 Cannabinoids and drug dependence.48 Pharmacology of nitric oxideE. Clementi.Chemistry and biosynthesis of nitric oxide.Biosynthesis of nitric oxide.Biochemistry of nitric oxide.Systemic and organ effects of nitric oxide.Pharmacology of nitric oxide.48.1 Chemistry of nitric oxide.48.2 Catalitic activity, molecular features and regulation of NO snthase.48.3 Nitric oxide and control of cell death.48.4 Role of NO in inflammation and in tumor pathology.49 Arachidonic acid metabolismG. Patrono and P.Patrignani.Arachidonic acid release from membrane lipids.Enzymatic metabolism of arachidonic acid .Non enzymatic metabolism of arachidonic acid.Eicosanoid receptors.49.1 Mechanism of action of glucocorticoids as antiinflammatory drugs.49.2 Mechanism of action aspirin as antithrombotic drug.SECTION 12 PHARMACOLOGY OF DEFENCE PROCESSES.50 Pharmacological modulation of the immune systemC. Riccardi and G. Migliorati.The immune response.Immunosuppressive drugs.Immunostimulant drugs.51 Mechanisms of action of anti–infective drugsF. Scaglione.Antibacterial drugs and their mechanisms of action.Antifungal drugs.Antiviral drugs.51.1 Mechanisms of antibiotic resistance in bacteria.SECTION 13 TOXICOLOGY AND DRUG INTERACTIONS.52 Introduction to ToxicologyH. Greim.Components of risk assessment.Toxicological evaluation of new and existing chemicals.Tests guidelines.General approach for hazard identification and risk assessment.Toxicological issues related to specific chemical classes.Classification and labelling of chemicals.The Threshold of Toxicological Concept.The precautionary principle.Conclusion.53 Drug interactionsA. Caputi, G. Fava and A. De Sarro.Pharmacokinetic drug interactions.Pharmacodynamic drug interactions.Chemical antagonism.Interactions between herbal remedies and drugs.Interactions between dietary supplements/components and drugs.53.1 Interactions between drugs and grapefruit juice.SECTION 14– DRUG DEVELOPMENT.54 Preclinical Research and development of new drugsE. Ongini.Technological innovation and scientific knowledge in today pharmaceutical research.The research strategies.The research stages.The development stages.The drugs in 2020.54.1 The significant contribution given by small research groups (start–ups and spin–offs).54.2 High–throughput screening.54.3 The beginning of a project on a new drug.54.4 The patent.54.5 Biotech drugs.54.6 Toxicology tests.54.7 Safety pharmacology: how to evaluate whether a new molecule will cause side effects on vital functions.55 Role of drug metabolism and pharmacokinetics in drug developmentS. Braggio and M. Pellegatti.Pharmacokinetics in drug discovery.Pharmacokinetics in the regulatory phase of drug development.Pharmacokinetics in clinical trials.Pharmacokinetiscs in drug formulation of generic equivalent drugs.New perspectives.56 Clinical testing  development of a new drug and methodology of drug trialsC. Patrono.Clinical development of a new drug.Observational studies and randomized clinical trials.The key role of the primary hypothesis.The choice of the primary end points.Sample size calculation.A look at the future

• ISBN: 978-1-118-76857-0
• Editorial: Wiley–Blackwell
• Encuadernacion: Cartoné
• Páginas: 720
• Fecha Publicación: 15/06/2015
• Nº Volúmenes: 1
• Idioma: Inglés