Basic and Clinical Pharmacology 12th edition by Bertram Katzung 007176402X 9780071764025

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ISBN 10: 007176402X
ISBN 13: 9780071764025
Author: Bertram G. Katzung

Basic & Clinical Pharmacology 12th Table of contents:

SECTION I: BASIC PRINCIPLES
CHAPTER 1: Introduction
CASE STUDY
FIGURE 1–1
THE HISTORY OF PHARMACOLOGY
Pharmacology & Genetics
PHARMACOLOGY & THE PHARMACEUTICAL INDUSTRY
GENERAL PRINCIPLES OF PHARMACOLOGY
THE NATURE OF DRUGS
The Physical Nature of Drugs
Drug Size
Drug Reactivity and Drug-Receptor Bonds
Drug Shape
FIGURE 1–2
TABLE 1–1: Dissociation constants (Kd) of the enantiomers and racemate of carvedilol.
Rational Drug Design
Receptor Nomenclature
DRUG-BODY INTERACTIONS
Pharmacodynamic Principles
A. Types of Drug-Receptor Interactions
FIGURE 1–3
B. Agonists That Inhibit Their Binding Molecules
C. Agonists, Partial Agonists, and Inverse Agonists
FIGURE 1–4
D. Duration of Drug Action
E. Receptors and Inert Binding Sites
Pharmacokinetic Principles
A. Permeation
FIGURE 1–5
TABLE 1–2: Some transport molecules important in pharmacology.
B. Fick’s Law of Diffusion
C. Ionization of Weak Acids and Weak Bases; the Henderson-Hasselbalch Equation
TABLE 1–3: Ionization constants of some common drugs.
TABLE 1–4: Body fluids with potential for drug “trapping” through the pH-partitioning phenomenon.
FIGURE 1–6
DRUG GROUPS
SOURCES OF INFORMATION
REFERENCES
CASE STUDY ANSWER

CHAPTER 2: Drug Receptors & Pharmacodynamics
CASE STUDY
MACROMOLECULAR NATURE OF DRUG RECEPTORS
RELATION BETWEEN DRUG CONCENTRATION & RESPONSE
Concentration-Effect Curves & Receptor Binding of Agonists
FIGURE 2–1
FIGURE 2–2
Receptor-Effector Coupling & Spare Receptors
Competitive & Irreversible Antagonists
FIGURE 2–3
Partial Agonists
FIGURE 2–4
Other Mechanisms of Drug Antagonism
SIGNALING MECHANISMS & DRUG ACTION
FIGURE 2–5
Intracellular Receptors for Lipid-Soluble Agents
FIGURE 2–6
Ligand-Regulated Transmembrane Enzymes Including Receptor Tyrosine Kinases
FIGURE 2–7
Cytokine Receptors
FIGURE 2–8
Ligand- and Voltage-Gated Channels
FIGURE 2–9
G Proteins & Second Messengers
FIGURE 2–10
TABLE 2–1: G proteins and their receptors and effectors.
FIGURE 2–11
Receptor Regulation
FIGURE 2–12
Well-Established Second Messengers
A. Cyclic Adenosine Monophosphate (cAMP)
FIGURE 2–13
B. Phosphoinositides and Calcium
FIGURE 2–14
C. Cyclic Guanosine Monophosphate (cGMP)
Interplay among Signaling Mechanisms
Phosphorylation: A Common Theme
RECEPTOR CLASSES & DRUG DEVELOPMENT
RELATION BETWEEN DRUG DOSE & CLINICAL RESPONSE
Dose & Response in Patients
A. Graded Dose-Response Relations
FIGURE 2–15
B. Shape of Dose-Response Curves
C. Quantal Dose-Effect Curves
FIGURE 2–16
Variation in Drug Responsiveness
A. Alteration in Concentration of Drug That Reaches the Receptor
B. Variation in Concentration of an Endogenous Receptor Ligand
C. Alterations in Number or Function of Receptors
D. Changes in Components of Response Distal to the Receptor
Clinical Selectivity: Beneficial versus Toxic Effects of Drugs
A. Beneficial and Toxic Effects Mediated by the Same Receptor-Effector Mechanism
B. Beneficial and Toxic Effects Mediated by Identical Receptors but in Different Tissues or by Different Effector Pathways
C. Beneficial and Toxic Effects Mediated by Different Types of Receptors
REFERENCES
CASE STUDY ANSWER

CHAPTER 3: Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action
CASE STUDY
FIGURE 3–1
TABLE 3–1: Pharmacokinetic and pharmacodynamic parameters for selected drugs. (See Speight & Holford, 1997, for a more comprehensive listing.)
PHARMACOKINETICS
FIGURE 3–2
Volume of Distribution
TABLE 3–2: Physical volumes (in L/kg body weight) of some body compartments into which drugs may be distributed.
Clearance
A. Capacity-Limited Elimination
B. Flow-Dependent Elimination
Half-Life
FIGURE 3–3
Drug Accumulation
Bioavailability
FIGURE 3–4
TABLE 3–3: Routes of administration, bioavailability, and general characteristics.
A. Extent of Absorption
B. First-Pass Elimination
C. Rate of Absorption
Extraction Ratio & the First-Pass Effect
Alternative Routes of Administration & the First-Pass Effect
THE TIME COURSE OF DRUG EFFECT
Immediate Effects
FIGURE 3–5
Delayed Effects
Cumulative Effects
THE TARGET CONCENTRATION APPROACH TO DESIGNING A RATIONAL DOSAGE REGIMEN
Maintenance Dose
FIGURE 3–6
Loading Dose
Example: Maintenance Dose Calculations
TARGET CONCENTRATION INTERVENTION: APPLICATION OF PHARMACOKINETICS & PHARMACODYNAMICS TO DOSE INDIVIDUALIZATION
Pharmacokinetic Variables
A. Absorption
The Target Concentration Strategy
B. Clearance
C. Volume of Distribution
D. Half-Life
Pharmacodynamic Variables
A. Maximum Effect
B. Sensitivity
INTERPRETATION OF DRUG CONCENTRATION MEASUREMENTS
Clearance
Dosing History
Timing of Samples for Concentration Measurement
Plasma Protein Binding: Is It Important?
Initial Predictions of Volume of Distribution & Clearance
A. Volume of Distribution
B. Clearance
Revising Individual Estimates of Volume of Distribution & Clearance
REFERENCES
CASE STUDY ANSWER

CHAPTER 4: Drug Biotransformation
WHY IS DRUG BIOTRANSFORMATION NECESSARY?
THE ROLE OF BIOTRANSFORMATION IN DRUG DISPOSITION
FIGURE 4—1
FIGURE 4–2
WHERE DO DRUG BIOTRANSFORMATIONS OCCUR?
MICROSOMAL MIXED FUNCTION OXIDASE SYSTEM & PHASE I REACTIONS
FIGURE 4–3
TABLE 4–1: Phase I reactions.
HUMAN LIVER P450 ENZYMES
FIGURE 4–4
TABLE 4–2: Human liver P450s (CYPs), and some of the drugs metabolized (substrates), inducers, and selective inhibitors.
Enzyme Induction
Enzyme Inhibition
PHASE II REACTIONS
TABLE 4–3: Phase II reactions.
METABOLISM OF DRUGS TO TOXIC PRODUCTS
FIGURE 4–5
CLINICAL RELEVANCE OF DRUG METABOLISM
Individual Differences
Genetic Factors
TABLE 4–4: Some examples of genetic polymorphisms in phase I and phase II drug metabolism.
A. Phase I Enzyme Polymorphisms
FIGURE 4–6
B. Phase II Enzyme Polymorphisms
C. The Role of Pharmacogenetic Testing in Clinically Safe & Effective Drug Therapy
Diet & Environmental Factors
Age & Sex
Drug-Drug Interactions during Metabolism
TABLE 4–5: Partial list of drugs that enhance drug metabolism in humans.
TABLE 4–6: Partial list of drugs that inhibit drug metabolism in humans.
Interactions between Drugs & Endogenous Compounds
Diseases Affecting Drug Metabolism
TABLE 4–7: Rapidly metabolized drugs whose
REFERENCES

CHAPTER 5: Development & Regulation of Drugs
FIGURE 5–1
THE PHARMACEUTICAL INDUSTRY
DRUG DISCOVERY
Drug Screening
PRECLINICAL SAFETY & TOXICITY TESTING
TABLE 5–1: Safety tests.
EVALUATION IN HUMANS
Confounding Factors in Clinical Trials
A. The Variable Natural History of Most Diseases
B. The Presence of Other Diseases and Risk Factors
C. Subject and Observer Bias and Other Factors
Drug Studies—The Types of Evidence*
The Food & Drug Administration
TABLE 5–2: Some major legislation pertaining to drugs in the United States.
Clinical Trials: The IND & NDA
Conflicts of Interest
Translational Research
Adverse Drug Reactions
Orphan Drugs & Treatment of Rare Diseases
REFERENCES

SECTION II: AUTONOMIC DRUGS
CHAPTER 6: Introduction to Autonomic Pharmacology
CASE STUDY
ANATOMY OF THE AUTONOMIC NERVOUS SYSTEM
FIGURE 6–1
FIGURE 6–2
NEUROTRANSMITTER CHEMISTRY OF THE AUTONOMIC NERVOUS SYSTEM
Cholinergic Transmission
FIGURE 6–3
TABLE 6–1: Some of the transmitter substances found in autonomic nervous system, enteric nervous system, and nonadrenergic, noncholinergic neurons.
Adrenergic Transmission
FIGURE 6–4
FIGURE 6–5
Neurotransmitter Uptake Carriers
FIGURE 6–6
Cotransmitters in Cholinergic & Adrenergic Nerves
AUTONOMIC RECEPTORS
NONADRENERGIC, NONCHOLINERGIC (NANC) NEURONS
FUNCTIONAL ORGANIZATION OF AUTONOMIC ACTIVITY
TABLE 6–2: Major autonomic receptor types.
Central Integration
Integration of Cardiovascular Function
FIGURE 6–7
TABLE 6–3: Direct effects of autonomic nerve activity on some organ systems. Autonomic drug effects are similar but not identical (see text).
Presynaptic Regulation
TABLE 6–4: Autoreceptor, heteroreceptor, and modulatory effects on nerve terminals in peripheral synapses.
Postsynaptic Regulation
FIGURE 6–8
PHARMACOLOGIC MODIFICATION OF AUTONOMIC FUNCTION
Pharmacology of the Eye
FIGURE 6–9
TABLE 6–5: Steps in autonomic transmission: Effects of drugs.
REFERENCES
CASE STUDY ANSWER

CHAPTER 7: Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs
CASE STUDY
FIGURE 7–1
SPECTRUM OF ACTION OF CHOLINOMIMETIC DRUGS
TABLE 7–1: Subtypes and characteristics of cholinoceptors.
MODE OF ACTION OF CHOLINOMIMETIC DRUGS
BASIC PHARMACOLOGY OF THE DIRECT-ACTING CHOLINOCEPTOR STIMULANTS
Chemistry & Pharmacokinetics
A. Structure
FIGURE 7–2
FIGURE 7–3
B. Absorption, Distribution, and Metabolism
TABLE 7–2: Properties of choline esters.
Pharmacodynamics
A. Mechanism of Action
FIGURE 7–4
B. Organ System Effects
TABLE 7–3: Effects of direct-acting cholinoceptor stimulants.
FIGURE 7–5
BASIC PHARMACOLOGY OF THE INDIRECT-ACTING CHOLINOMIMETICS
Chemistry & Pharmacokinetics
A. Structure
FIGURE 7–6
FIGURE 7–7
B. Absorption, Distribution, and Metabolism
TABLE 7–4: Therapeutic uses and durations of action of cholinesterase inhibitors.
Pharmacodynamics
A. Mechanism of Action
B. Organ System Effects
CLINICAL PHARMACOLOGY OF THE CHOLINOMIMETICS
Clinical Uses
A. The Eye
B. Gastrointestinal and Urinary Tracts
C. Neuromuscular Junction
D. Heart
E. Antimuscarinic Drug Intoxication
F. Central Nervous System
Toxicity
A. Direct-Acting Muscarinic Stimulants
B. Direct-Acting Nicotinic Stimulants
C. Cholinesterase Inhibitors
SUMMARY Drugs Used for Cholinomimetic Effects
PREPARATIONS AVAILABLE
DIRECT ACTING CHOLINOMIMETICS
CHOLINESTERASE INHIBITORS
REFERENCES
CASE STUDY ANSWER

CHAPTER 8: Cholinoceptor-Blocking Drugs
CASE STUDY
BASIC PHARMACOLOGY OF THE MUSCARINIC RECEPTOR-BLOCKING DRUGS
Chemistry & Pharmacokinetics
A. Source and Chemistry
FIGURE 8–1
FIGURE 8–2
B. Absorption
C. Distribution
D. Metabolism and Excretion
Pharmacodynamics
A. Mechanism of Action
TABLE 8–1: Muscarinic receptor subgroups important in peripheral tissues and their antagonists.
B. Organ System Effects
FIGURE 8–3
FIGURE 8–4
FIGURE 8–5
CLINICAL PHARMACOLOGY OF THE MUSCARINIC RECEPTOR-BLOCKING DRUGS
Therapeutic Applications
A. Central Nervous System Disorders
B. Ophthalmologic Disorders
TABLE 8–2: Antimuscarinic drugs used in ophthalmology.
C. Respiratory Disorders
D. Cardiovascular Disorders
E. Gastrointestinal Disorders
F. Urinary Disorders
TABLE 8–3: Antimuscarinic drugs used in gastrointestinal and genitourinary conditions.
G. Cholinergic Poisoning
H. Other Applications
Adverse Effects
Contraindications
BASIC & CLINICAL PHARMACOLOGY OF THE GANGLION-BLOCKING DRUGS
Chemistry & Pharmacokinetics
FIGURE 8–6
Pharmacodynamics
A. Mechanism of Action
B. Organ System Effects
Clinical Applications & Toxicity
SUMMARY Drugs with Anticholinergic Actions
PREPARATIONS AVAILABLE
ANTIMUSCARINIC ANTICHOLINERGIC DRUGS
GANGLION BLOCKERS
CHOLINESTERASE REGENERATOR
REFERENCES
Treatment of Anticholinesterase Poisoning
CASE STUDY ANSWER

CHAPTER 9: Adrenoceptor Agonists & Sympathomimetic Drugs
CASE STUDY
MOLECULAR PHARMACOLOGY UNDERLYING THE ACTIONS OF SYMPATHOMIMETIC DRUGS
FIGURE 9–1
TABLE 9–1: Adrenoceptor types and subtypes.
Receptor Types
A. Alpha Receptors
FIGURE 9–2
B. Beta Receptors
C. Dopamine Receptors
Receptor Selectivity

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