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Contents
Preface ...................................................... (vii)Acknowlegement ....................................... (ix)Abbreviations ..................................... (xxxix)
PART IGENERAL PRINCIPLES
Chapter - 1Branches and Divisions ofPharmacology
Introduction .................................................. 3Drug ................................................................ 3
Drug Sources ................................................. 4Drug Nomenclature ..................................... 4The Nature of Drugs .................................... 4
Branches of Pharmacology ......................... 5Hypersensitivity ........................................... 9
Type I Hypersensitivity ............................... 9Type II Hypersensitivity ............................10Type III Hypersensitivity ...........................10Type IV Hypersensitivity ...........................11
Drug Response and Factorsaffecting Drug Response ........................... 12Important Factors ModifyingDrug Action ................................................ 12
Chapter - 2Pharmacokinetics of DrugsBiotransport of Drug ................................. 22Composition and Structure ofMembranes .................................................. 22
Lipids ...........................................................22
Proteins ........................................................23Transfer through the Lipid Bilayer ..........23Transfer through MembraneProtein Structures .......................................25Transport by Exocytosis andEndocytosis .................................................26
Drug Absorption ........................................ 27Distribution of Drugs ................................ 30
Drug Distribution from Blood...................31Binding to Proteins .....................................31Tissue Distribution of Drugs ....................32Excretion of Drugs ......................................34Different Routes of Drug Excretion ..........35
Other Routes of Excretion ........................ 38Milk Excretion .............................................38Sweat Excretion ..........................................38Mammary Excretion ...................................38Excretion by various Secretions ................38Artificial Methods of Excretion ................39Digestive Excretion.....................................39Accelerated Renal Excretion .....................39Artificial Excretion .....................................39
Theoretical Pharmacokinetics .................. 39References .................................................... 41
Chapter - 3Drug Receptors and PharmacodynamicsIntroduction ................................................ 42Drug-Receptor Complex Nomenclature 42
Some Characteristics of Receptors ...........43Drug Receptor Interactions .......................55Receptor Site Theories ................................56
Pharmacodynamics .................................... 57References .................................................... 59
Contents(xii)
Chapter - 4Drug BiotransformationIntroduction ................................................ 60
Sites of Drug Metabolism ...........................60Drug Metabolizing Enzymes ....................61Phase I Reactions........................................62Oxidative Reactions ...................................64Reductive Reactions ...................................68Hydrolytic Reactions .................................68Phase II Reactions ......................................70
Factors AffectingBiotransformation of Drug ....................... 77
Enzyme Inhibition ......................................78Presystemic Metabolism/First PassEffect/Route of Administration ................79Genetic Variations ......................................79Species Differences .....................................79Exposure to Pollutants fromEnvironment or Industry ...........................79Age................................................................79Sex ................................................................80Drug-Drug Interaction ...............................80Nutrition ......................................................80Pathological Conditions ............................80Circadian Rhythm ......................................80
References .................................................... 80
PART IIDRUGS AFFECTING AUTONOMIC
NERVOUS SYSTEM
Chapter - 5General Considerations ofAutonomic Nervous SystemAnatomy ...................................................... 83Sympathetic Division ................................. 83Parasympathetic Division ......................... 84Sensory Neurons ........................................ 85Motor Neurons ........................................... 85Function........................................................ 86
Sympathetic Nervous System ...................86Parasympathetic Nervous System ...........86
Neurotransmitters and Pharmacology ... 86References .................................................... 89
Chapter - 6Cholinergic DrugsThe Cholinergic Neuron ........................... 90
Neurotransmission atCholinergic Neurons..................................90
Cholinergic Receptors(Cholinoceptors) ......................................... 92
Muscarinic Receptors (M) .........................92Molecular Mechanism atMuscarinic Receptors ................................92Nicotinic Receptors ....................................93Molecular Mechanisms/SignalTransduction at Nicotinic Receptors .......93Parasympathomimetic Drugs orCholinergic Drugs orCholinomimetic Drugs...............................93Acetylcholine Effects ..................................95Muscarinic Effects ......................................95Cardiac Effects ............................................95Vascular Effects ..........................................95Effects on Smooth Muscles(Except Vascular) ........................................95Effects on Secretions (Receptors M3) ........96Effects on the Eye (Receptors M3) .............96Central Effects .............................................96Nicotinic Effects ..........................................96Autonomic Ganglia Effects .......................96Neuromuscular Junction Effects ..............96Central Nervous System Effects ................98
Parasympathomimetic Drugs ................... 98Directly acting Cholonergic Drugs ..........98Cholinomimetic Alkaloids ........................99Acetylcholinestrase ................................ 102Reversible Inhibitors ............................... 102Mechanisms of Action of Indirect(Reversible) Cholinergic Agonists ......... 104Irreversible Inhibitors .............................. 104Anticholinesterase/OrganophosphorusPoisoning and Treatment ....................... 105
References .................................................. 106
Chapter - 7Muscarinic Receptor Blocking DrugsClassification ............................................. 107Basic Pharmacology of MuscarinicReceptor Blocking Drugs ........................ 108
Pharmacokinetics .................................... 108
Contents (xiii)
Mechanism of Action .............................. 108Effects ........................................................ 108
Toxicity of Antimuscarinic Drugs ......... 112Predictable Toxicities .............................. 112Unpredictable Toxicities ......................... 112
Clinical Uses .............................................. 112Mydriatic Agents ..................................... 112Gastric Acid Secretion Inhibitors .......... 112Bronchodilators ....................................... 113With Vesical Indications ........................ 113Used as Antispasmodics ........................ 113Used as Antiparkinsonians ................... 113Uses in Urology ....................................... 113Uses in Anaesthesiology ........................ 113Other Drugs.............................................. 116
Contraindications and Cautions ............ 116References .................................................. 116
Chapter - 8Adrenergic DrugsThe Adrenergic Neuron.......................... 117
Neurotransmission atAdrenergic Neurons ............................... 117
Synthesis, Storage andRelease of Catecholamines ...................... 118Metabolism and Distributionof Catecholamines .................................... 119Adrenergic Receptors .............................. 119α Receptors ............................................... 121β Receptors ................................................ 121Classification of Adrenergic Agonists . 122
Structure Activity Relationship ofAdrenergic Drugs ............................... 123
Direct-Acting Agonists ............................ 124Epinephrine (EP) ..................................... 124Norepinephrine (NE) .............................. 126Dopamine ................................................. 127Amphetamine .......................................... 128Ephedrine ................................................. 128Isoproterenol ............................................ 129
Selective Adrenergic Agonists .............. 129Phenylephrine, Metaraminol,and Methoxamine ................................... 129Dobutamine.............................................. 129Terbutaline and Albuterol ...................... 130References ............................................ 130
Chapter - 9Adrenergic Blocking DrugsClassification ofSympatholytic Drugs ............................... 131Alpha-AdrenergicAntagonists (Blockers) ............................ 131
Classification ........................................... 131Quinazoline Derivatives ......................... 131Imidazoline Derivative ........................... 133Haloalkylamines ..................................... 133Clinical Pharmacology of α-receptorBlocking Drugs ........................................ 134β-Adrenergic Antagonists ...................... 135Nonselective-β AdrenergicReceptor Antagonists .............................. 139Selective-b1 Adrenergic ReceptorAntagonists .............................................. 139Therapeutic uses for Beta AdrenergicReceptor Antagonists (Blockers) ........... 140Hyperthyroidism ..................................... 140Glaucoma ................................................. 140Anxiety States .......................................... 141Migraine.................................................... 141Angina Pectoris ....................................... 141Acute Myocardial Infarction .................. 141Supraventricular Tachycardias andVentricular Dysrhythmias ...................... 141Hypertension ........................................... 141Adverse Effects of β AdrenergicReceptor Antagonists .............................. 142Drugs with Combined α-andβ-Blocking Activity .................................. 142Labetalol ................................................... 142Other Compounds ................................... 144
References .................................................. 144
Chapter - 10Ganglionic Stimulating andBlocking AgentsIntroduction .............................................. 145
Mechanism of Action .............................. 145Pharmacological Actions ......................... 146
Peripheral Nervous System ................... 146Central Nervous System ......................... 146Cardiovascular System ........................... 147Gastrointestinal Tract ............................. 147Exocrine Glands ...................................... 147
Contents(xiv)
Pharmacokinetics .................................... 147Acute Nicotine Poisoning ...................... 147
Therapy ...................................................... 148Lobeline .................................................... 148Other Ganglionic Stimulants ................. 148
Ganglion-Blocking Drugs ....................... 149Classification ........................................... 149Chemistry and Pharmacokinetics ......... 149Pharmacodynamics ................................ 150Organ System Effects ............................... 150Clinical Applications and Toxicity ....... 150
References .................................................. 152
Chapter - 11Skeletal Muscle RelaxantsIntroduction .............................................. 153Neuromuscular Physiology .................... 153Classification ............................................. 154Mechanism of SkeletalMuscle Contraction .................................. 154Nondepolarizing Agents ........................ 155
Mechanism of Action .............................. 155Pharmacological Actions ....................... 155Clinical Uses ............................................ 155Adverse Effects and Precautions ........... 155
Other NondepolarizingBlockers of Importance ........................... 156
Classification According toDuration of Action .................................. 156
Depolarizing Agents ................................ 158Drugs: Suxamethonium(succinylcholine) Decamethonium ....... 158Succinylcholine ....................................... 158Uses of NeuromuscularBlocking Drugs ........................................ 160
Central Acting Skeletal MuscleRelaxants (Spasmolytic Drugs) .............. 161Methocarbamol ......................................... 162Baclofen ...................................................... 162Dantrolene ................................................. 162Botulinum Toxin Type A,B ..................... 162Benzodiazepines (diazepam,lorazepam, clonazepam, etc.) ................. 163Tizanidine .................................................. 163
Drugs Used to Treat AcuteLocal Muscle Spasm ................................. 163
Cyclobenzaprine ..................................... 164Orphenadrine .......................................... 165Metaxalone ............................................... 165Carisoprodol ............................................ 165
Other Centrally ActingSpasmolytic Drugs ................................... 165References .................................................. 165
PART IIIDRUGS AFFECTING
CENTRAL NERVOUS SYSTEM
Chapter - 12General Considerations ofCentral Nervous SystemMacroanatomy .......................................... 169Microanatomyof the Brain ...................... 170Central Neurotransmitters ........................... 171
Biogenic Amines ...................................... 171Acetylcholine ........................................... 178GABA and Glycine.................................. 178Amino Acids ............................................ 185Neuropeptides (polypeptides) ............... 187Purine Nucleotides .................................. 187P2 Receptors and Actions ....................... 189Peptides .................................................... 190
References .................................................. 191
Chapter - 13Neurodegenerative DiseasesIntroduction .............................................. 192Alzheimer’s Disease ................................. 192
Pathophysiology ..................................... 192Symptoms ................................................. 193Treatment ................................................. 193Parkinson’s Disease ................................ 195Pathophysiology ..................................... 195Symptoms ................................................. 195Treatment ................................................. 196
Huntington Disease ................................. 205Symptoms and Stages of HD ................. 205The Stages of HD ..................................... 206Diagnosis ................................................. 207
Contents (xv)
Juvenile Huntington’s Disease .............. 207Symptomatic Treatment andManagement ............................................ 207
References .................................................. 210
Chapter - 14General AnaestheticsPrinciple of General Anaesthesia .......... 212Stages of Anesthesia ................................ 212Theory of General Anaesthetics ............ 214
Lipid Theory ............................................ 214Classification ............................................. 215Intravenous Anesthetics orInduction Agents ...................................... 215
Inhaled Anaesthetics .............................. 220Preanaesthetic Medication ...................... 226
Objectives ofPreanaesthetic Medication ..................... 226Sedatives/Anxiolytics ............................ 226Opioid Analagesics ................................. 227Anticholinergic Drugs ............................ 227Antiemetics–Antiemetic Effect ............... 227
References .................................................. 228
Chapter - 15Sedative Hypnotics andAnxiolytic DrugsSleep ............................................................ 229
Genesis of Sleep ....................................... 229Classification ............................................. 230Azapirones ................................................ 230
Benzodiazepines ..................................... 231Barbiturates ............................................... 236
Other BenzodiazepineReceptor Agonists ................................... 238
Sedatives and Anxiolytics withother Major Uses ...................................... 238
Antihistamines ..................................... 238β - Adrenoceptor Blocking Agents .. 239Antidepressants .................................. 239
Older Sedative–Hypnotics andAnxiolytic Agents ..................................... 239Non-prescription Drugs .......................... 239References .................................................. 240
Chapter - 16NeurolepticsIntroduction .............................................. 241
Schizophrenia .......................................... 241Symptoms ................................................. 241Types ......................................................... 242
Theories of Schizophrenia ...................... 242Dopamine Hypothesis ............................ 242Serotonin Hypothesis ............................. 242Glutamate Hypothesis ............................ 243
Definitions ................................................. 243Ideal Antipsychotic ................................. 243
Classification ofAntipsychotic Drugs ................................ 243
Distinction between ‘typical’ and‘atypical’ groups is not clearly defined,but rests on: .............................................. 243Mechanism of Action .............................. 244
Phenothiazines .......................................... 245Chlorpromazine ...................................... 245Pharmacological Effectsand Mechanism ....................................... 246Pharmacokinetics .................................... 246Adverse Effects ........................................ 246Therapeutic Uses ..................................... 247Phenothiazines - Drug Interactions ...... 249
Nonphenothiazines .................................. 249First-Generation “Typical”Antipsychotics ......................................... 249Second-Generation “Atypical”Antipsychotics ......................................... 249
References .................................................. 253
Chapter - 17AntidepressantsIntroduction .............................................. 254Causes for Depression ............................. 254The Monoamine Theory .......................... 254Symptoms .................................................. 254Treatment .................................................. 255
Classification ........................................... 255Antidepressants ...................................... 255
Selective SerotoninReuptake Inhibitors ................................. 255
Mechanism of Action .............................. 255
Contents(xvi)
Pharmacokinetics .................................... 256Therapeutic Uses ..................................... 256Adverse Effects ........................................ 256Drug Interactions ..................................... 257
Serotonin-NorepinephrineReuptake Inhibitors ................................. 257
Types of SNRIs ........................................ 257Mechanism of Action .............................. 257Adverse Effects ........................................ 257
Atypical Antidepressants ........................ 257Mechanism of Action .............................. 257Atypical Antidepressants Approvedto Treat Depression ................................. 258Adverse Effects of AtypicalAntidepressants ...................................... 258
Tricyclic andTetracyclic Antidepressants ................... 258
Mechanism of Action .............................. 258Cyclic Antidepressants Approved toTreat Depression ..................................... 258Adverse Effects ofTricyclic Antidepressants ...................... 259
MAO Inhibitors ........................................ 259Mechanism of Action .............................. 259Risks are Associated withMAO Inhibitors ........................................ 259Medications to Avoid .............................. 259Foods to Avoid ......................................... 260Adverse Effects ........................................ 260
References .................................................. 260
Chapter - 18Antiepileptic DrugsIntroduction .............................................. 261Pathophysiology ....................................... 261Types of Seizures ..................................... 261
Partial Seizures ........................................ 261Generalised Seizures ............................... 262Causes for Acute Seizures ...................... 263
Treatment .................................................. 264Strategies ................................................... 264Classification of Antiepileptics .............. 265Sodium Channel Blocking Agents ......... 267
Phenytoin ................................................. 267Carbamazepine........................................ 268Oxcarbazepine ......................................... 269
Lamotrigine .............................................. 269Zonisamide .............................................. 269Topiramate ............................................... 270Sodium Valproate or Valproic Acid ...... 270
Drugs that Primarily Enhancethe Action of GABA ................................ 271
Benzodiazepines ..................................... 271Vigabatrin ................................................. 272Tiagabine .................................................. 272Phenobarbital andPrimidone (Mysoline) ............................. 272
Agents that BlockT-Calcium Channels ................................. 273
Ethosuximide ........................................... 273Agents whose Mechanism ofAction is not Known ................................ 273
Felbamate ................................................. 273Gabapentin .............................................. 273Levetiracetam ........................................... 274Anticonvulsant Drugs and Pregnancy. 274
Treatment of Febrile Seizures ................ 275Treatment of Status Epilepticus............. 275References .................................................. 275
Chapter - 19Opioid AnalgesicsIntroduction .............................................. 276Endogenous Opioids ............................... 277
Enkephalins, Endorphins,Dynorphins, Endomorphins .................. 278
Opioid Receptors ...................................... 278Mechanism of OpioidReceptor Function ................................... 279Classification ofOpioid Analgesic Drugs ......................... 279Pharmacokinetics .................................... 279Cellular Mechanisms of Action ............. 280Pharmacological Effects ......................... 280Tolerance and Physical Dependence.... 281Morphine .................................................. 282
Other Opioids ........................................... 283Meperidine or Pethidine ......................... 283Methadone ............................................... 284Fentanyl .................................................... 284Heroin ....................................................... 284Codeine ..................................................... 284
Contents (xvii)
Oxycodone ............................................... 284Propoxyphene .......................................... 285
Mixed Agonist-Antagonist andPartial Agonists ........................................ 285
Buprenorphine ........................................ 285Pharmacokinetics .................................... 285Antagonists .............................................. 286
References .................................................. 287
Chapter - 20Non Steroidal Anti-inflammatory DrugsIntroduction .............................................. 288Nonsteroidal Anti-inflammatoryDrugs (NSAIDs) ....................................... 289
Mechanism of Action .............................. 289Anti-inflammatory Effect ........................ 289Analgesic Effect ....................................... 290Antipyretic Effect ..................................... 290Classification ........................................... 290Mechanism of Action of Non-steroidalAnti-inflammatory Drugs (NSAIDs) ..... 290
Salicylates .................................................. 290Chemistry ................................................. 290Mechanism of Action .............................. 291Pharmacokinetics .................................... 292Pharmacological Effects ......................... 292Overdose and Other Adverse Effects .... 293Therapeutic Uses ..................................... 294Drug Interactions ..................................... 294
P-Aminophenol Derivatives ................... 294Pharmacokinetics .................................... 294Mechanism of Action .............................. 295Pharmacological Effects ......................... 295Adverse Effects ........................................ 295Therapeutic Uses ..................................... 295Contraindications ................................... 295
Indoles (indomethacin) andRelated Compounds ................................ 296
Chemistry and Mechanism of Action ... 296Pharmacokinetics .................................... 296Indomethacin ........................................... 296Sulindac .................................................... 296Ketorolac ................................................... 297Etodolac .................................................... 297Fenamates ................................................. 297
Arylpropionic Acid Derivatives ............ 298Chemistry and Mechanism of Action ... 298
Clinical Uses, Adverse Effectsand Contraindications ............................ 299Ibuprofen .................................................. 299Fenoprofen ............................................... 299Naproxen .................................................. 299Ketoprofen ................................................ 300Flurbiprofen ............................................. 300
Pyrazolone Derivatives ........................... 300Oxicam Derivatives .................................. 300Acetic Acid Derivatives .......................... 301Miscellaneous Agents .............................. 301COX-2 Inhibitors ...................................... 302
Chemistry ................................................. 302Mechanism of Action .............................. 302Pharmacological Effects andClinical Uses ............................................ 302Adverse Effects ........................................ 303Contraindications ................................... 303Rofecoxib .................................................. 303
References .................................................. 303
Chapter - 21CNS StimulantsIntroduction .............................................. 304
Classification ........................................... 304Analeptic Stimulants .............................. 305Mechanism of Action .............................. 305Pharmacokinetics .................................... 306Clinical Uses ............................................ 306
Psychomotor Stimulants .......................... 306Pharmacokinetics .................................... 307Clinical Uses ............................................ 307Adverse Effects ........................................ 307Xanthines ................................................. 307Pharmacokinetics .................................... 308Mechanism of Action .............................. 308Clinical Uses ............................................ 309Adverse Effects ........................................ 309Abuse of Xanthines ................................. 309Drug Interactions ..................................... 309
References .................................................. 309
Chapter - 22Drug Dependence and Drug AbuseOpioids ....................................................... 311
Extent and Pattern of Abuse .................. 311
Contents(xviii)
Pharmacological Aspects ....................... 312Tolerance and Dependence .................... 312Treatment of Opioid Dependence ......... 312
Stimulants .................................................. 313Extent and Pattern of Abuse .................. 313Pharmacological Aspects ....................... 313Mechanism of Action .............................. 313Tolerance and Dependence .................... 314Other Adverse Effects ofChronic Abuse ......................................... 314Nicotine .................................................... 314
Sedative–Hypnotics ................................. 314Pharmacological Aspects ....................... 314Tolerance and Dependence .................... 315
Ethanol ....................................................... 315Chemistry ................................................. 315Absorption, Distribution, Metabolismand Excretion ........................................... 316Mechanism of Action .............................. 316Pharmacological Actions onCentral Nervous System ......................... 317Other Body Systems ................................ 317Adverse Effects ........................................ 317Treatment for Acute Intoxication .......... 318Alcoholism ............................................... 318
Marijuana ................................................... 319Chemistry ................................................. 319Pharmacokinetic Aspects ....................... 319Mechanism of Action .............................. 319Pharmacological Actions onCentral Nervous System ......................... 319Other Organ Systems .............................. 320Adverse Effects ........................................ 320
Hallucinogens ........................................... 320Extent and Pattern of Abuse .................. 321Pharmacological Aspects ....................... 321Tolerance and Dependence .................... 322Treatment Strategies ................................ 322Mechanism of Action .............................. 322
Inhalants ..................................................... 322Designer Drugs ......................................... 323Anabolic Steroids ..................................... 323References .................................................. 323
Chapter - 23Local AnaestheticsIntroduction .............................................. 324
Chemistry ................................................. 324Classification ........................................... 324
Combinations ............................................ 325Mechanism of Action .............................. 325
Various Techniques ofLocal Anesthesia ....................................... 327
Clinical Techniques Include .................. 327Pharmacokinetics ...................................... 328Adverse Effects ........................................ 329
Localized Adverse Effects ...................... 329General Adverse Effects .......................... 329Central Nervous System ......................... 329Cardiovascular System ........................... 330Hypersensitivity/Allergy ....................... 330Methemoglobinemia ............................... 330
Specific Uses .............................................. 330Acute Pain ................................................ 330Chronic Pain ............................................ 330Surgery and Dentistry ............................. 330Other Uses ................................................ 331
Factors Affecting LocalAnaesthetic Activity Clinically .............. 331
Dose ........................................................... 331Addition of Vasoconstrictors ................. 331Site of Injection ......................................... 332Carbonation and pH Adjustment ......... 332Mixtures of Local Anesthetics ............... 332Pregnancy................................................. 332
Medication Interactions withLocal Anesthetics ..................................... 333References .................................................. 333
PART IVDRUGS AFFECTING ON
CARDIOVASCULAR SYSTEM
Chapter - 24Drugs Used in Heart FailureIntroduction .............................................. 337Pathophysiology of Heart Failure ......... 338
Preload ...................................................... 338Afterload ................................................... 338
Contents (xix)
Structural Changes in Chronic CHF ..... 338Classification of Drugs used in CHF .... 340
Cardiac Glycosides .................................. 341Structure of Cardiac Glycosides ............ 341Pharmacological Actions ....................... 342Therapeutic Drug Monitoring ............... 345Therapeutic uses of Digitalis ................. 346Adverse Effects and Toxicity ................. 347
Other Inotropic Drugs ............................. 348Dobutamine.............................................. 348Dopamine ................................................. 349
Inodilators (Phophodiesterase–IIIinhibitors) .................................................. 349
Inamrinone (Amrinone) .......................... 349Milrinone .................................................. 349Enoximone ............................................... 350
Role of Vasodilators in CHF .................. 350Role of Diuretics in CHF ......................... 352
Vasopeptidase Inhibitors ....................... 352Thiazides .................................................. 352Loop Diuretics ......................................... 353Limitations of diuretics ........................... 353
Role of Aldosterone Antagonists/K+ Sparing Diuretics ................................. 353
Eplerenone ............................................... 354Role of Angiotensin ConvertingEnzyme Inhibitors (ACE-Is) ................... 354Beneficial Effects of ACE-Is .................... 356Adverse Effects of ACE-Is ....................... 356Angiotensin Receptor Blockers(ARBs) in CHF ......................................... 356Contraindications and Precautionswith ACE-Is and ARBs ........................... 356
References .................................................. 357
Chapter - 25Antiarrhythmic DrugsElectrophysiology - Resting Potential .. 358
Cardiac Action Potential ........................ 359Arrhythmogenic Mechanisms ................ 359
Abnormal Automaticity .......................... 359Triggered Activity .................................... 359Classification of Antiarrhythmic Drugs 360
Class IA ...................................................... 362Quinidine ................................................. 362Procainamide ........................................... 364
Disopyramide .......................................... 365Moricizine ................................................ 367
Class IB ....................................................... 369Lidocaine .................................................. 369Phenytoin ................................................. 370Tocainide .................................................. 371Mexiletine ................................................. 372
Class IC ...................................................... 373Flecainide ................................................. 373Propafenone ............................................. 374
Class II ........................................................ 376Propranolol .............................................. 376Acebutolol ................................................ 378Esmolol ..................................................... 378
Class III ...................................................... 379Bretylium .................................................. 379Amiodarone ............................................. 380Sotalol ....................................................... 382Ibutilide Fumarate ................................... 384
Class IV ...................................................... 385Verapamil ................................................. 385
References .................................................. 386
Chapter - 26Antianginal DrugsTypes of Angina Pectoris ........................ 387
Classic Angina ........................................ 387Variant Angina ........................................ 387Unstable Angina ..................................... 387Classification of Antianginal Drugs ..... 388
Organic Nitrates ....................................... 388Classification of Nitrates ........................ 388Adverse Effects ........................................ 390Clinical Uses ............................................ 390Contraindications ................................... 391Individual Nitrates .................................. 391
Beta-adrenergic Blocking Agents ......... 392Mechanism of Action .............................. 392Adverse Effects ........................................ 393Therapeutic uses of Beta-Blockers ......... 393Contraindications ................................... 393
Calcium ChannelBlocking Agents (CCBs) ....................... 394
Mechanism of Action .............................. 395Pharmacokinetics .................................... 395Adverse Effects ........................................ 395
Contents(xx)
Therapeutic use ofCalcium Channel Blockers ..................... 395Contraindications ................................... 395
Ranolazine ................................................. 396Mechanism of Action .............................. 396Adverse Effects and Contraindications 396Clinical Uses ............................................ 397
Adjunctive Antianginal Drugs ............... 397Aspirin ...................................................... 397Antilipemics ............................................. 397Antihypertensives ................................... 397
Combination Therapy ............................. 397Nitrates and Beta Blockers ..................... 397Calcium Channel Blockers andBeta Blockers ............................................ 397Calcium Channel Blockers and Nitrates397Drug Interactions of Antianginals ........ 397
Nonpharmacological Managementof Angina ................................................... 398References .................................................. 398
Chapter - 27Antihypertensives
Introduction ......................................... 399Classification ofHypertension for Adults ......................... 399
Types of Hypertension............................ 400Primary Hypertension ............................ 400Secondary Hypertension ........................ 400Malignant Hypertension ........................ 400Isolated Systolic Hypertension .............. 400White Coat Hypertension ....................... 400Resistant Hypertension .......................... 400
Potential Sites of Action forAntihypertensive Drugs .......................... 401Diuretics ..................................................... 402
Introduction ............................................. 402Mechanism of Action .............................. 404Advantages .............................................. 404Special Indications .................................. 404Chlorothiazide ......................................... 404Furosemide (Lasix), Bumetanide(Bumex) and Ethacrynic Acid (Edecrin) 404Therapeutic Uses ..................................... 405Pulmonary and Systemic Edema .......... 406Centrally Acting Drugs ........................... 406
α-Methyldopa .......................................... 406Clonidine and Related Drugs ................ 407
Adrenergic Neuron Blockers ................. 408Guanethidine ........................................... 408
Catecholamine Depletors ........................ 410Reserpine .................................................. 410
Drugs Acting onAdrenergic Receptors .............................. 411
Both Alpha andBeta Adrenergic Blockers ........................ 411Alpha Adrenergic Blockers .................... 411Beta Adrenergic Blocking Agents .......... 413
Drugs Acting Directly onVasular Smooth Muscle ........................... 417
Nitrodilators ............................................ 417Specific Drugs .......................................... 419Calcium Channel Blockers ..................... 419
Drugs Acting onRenin Angiotensin System ...................... 422
ACE Inhibitors ......................................... 422Angiotensin II Receptor Antagonists .... 426Renin Inhibitors ...................................... 427
References .................................................. 434
Chapter - 28Hypolipidemic DrugsIntroduction .............................................. 435Hyperlipidemia......................................... 435Classification ofHypolipidemic Drugs .............................. 437H M G – CoA ReductaseInhibitors (Statins) ................................... 437
Mechanism of Action .............................. 437Pharmacological Actions ....................... 439Adverse Effects ........................................ 440Clinical Uses ............................................ 440Contraindications ................................... 440Drug Interactions ..................................... 441
Fibric Acid Derivative (Fibrates) .......... 441Mechanism of Action .............................. 441Pharmacological Actions ....................... 443Pharmacokinetics .................................... 443Adverse Effects ........................................ 443Clinical Uses ............................................ 443Drug Interactions ..................................... 444
Contents (xxi)
Omega-3 Fatty Acids ............................... 444Mechanism of Action .............................. 444Clinical Uses ............................................ 445
Nicotinic Acid (Niacin) ............................ 446Mechanism of Action .............................. 446Pharmacological Actions ....................... 447Adverse Effects ........................................ 447Therapeutic Uses ..................................... 447
Cholesterol Uptake Inhibitors ............... 447Ezetimibe .................................................. 447
Bile Acid Binding Resins (BAS) ............. 448Mechanism of Action .............................. 449Pharmacological Actions ....................... 449Pharmacokinetics .................................... 449Adverse Effects ........................................ 449Contraindications ................................... 449Drug Interactions ..................................... 450Probucol .................................................... 450
Antihyperlipidemic Combinations ........ 450Indications ............................................... 450Advantages .............................................. 450
References .................................................. 451
PART VDRUGS AFFECTING
HAEMOSTASIS AND THROMBOSIS
Chapter - 29Drugs and Blood CoagulationIntroduction .............................................. 455
Normal Haemostasis .............................. 455Pathological Thrombus Formation ....... 456
Blood Clotting Factors ............................ 456Intrinsic Pathway .................................... 456Extrinsic Pathway ................................... 456Classification of Drugs ........................... 457
Anticoagulants .......................................... 457Features of an Ideal Anticoagulant ....... 457Oral Anticoagulants(Coumarin Anticoagulants) ................... 457Heparin ..................................................... 460
Newer Anticoagulants ............................. 464Direct Thrombin Inhibitors (DTIs) ........ 464Hirudin and its Derivatives ................... 466Bivalirudin ............................................... 466
Argatroban ............................................... 467Clinical Indications forAnticoagulant Therapy .......................... 469
Antiplatelet Agents .................................. 469Antiplatelet Drug Targets ...................... 469Aspirin ...................................................... 470Thienopyridines ...................................... 470Dipyridamole ........................................... 471Glycoprotein IIb/IIIa Inhibitors ............. 471
Thrombolytic Agents ............................... 471Individual Agents ................................... 473
References .................................................. 474
Chapter - 30Hemopoietic Drugs andPlasma Volume ExpandersIntroduction .............................................. 475Classification ofHematopoietic Drugs .............................. 475
Drugs for Anemia .................................... 475Hematopoietic Growth Factors ............. 475Anemia ...................................................... 476Causes of Anemia .................................... 476Classification of Anemia ........................ 476Diagnosis ................................................. 476
Drugs for Treatment ofAnemia (Hematinics) ............................... 477
Iron ............................................................ 477Deferoxamine ........................................... 479Vitamin B12 ............................................... 479Chemistry ................................................. 480Folic Acid ................................................. 481
Hematopoetic Growth Factors .............. 482Erythropoietin .......................................... 482Myeloid Growth Factors (ColonyStimulating Factors – CSFs) ................... 484Megakaryocyte Growth Factors ............. 485Thrombopoietin: Eltrombopag(Promacta®) ............................................. 486
Plasma Volume Expanders ..................... 487Mechanism of Action ofPlasma Volume Expanders .................... 488Ideal Plasma Expanders ......................... 488Preparations of PlasmaVolume Expanders .................................. 488Crystalloid Fluids .................................... 488
Contents(xxii)
Which Plasma VolumeExpander is Best? .................................... 496Potential Complications ......................... 496
References .................................................. 498
PART VI
DRUGS AFFECTING RENAL FUNCTION
Chapter - 31Diuretics and AntidiureticsRenal Physiology ...................................... 501
Glomerular Filtration .............................. 501Tubular Reabsorption and Secretion .... 501Reabsorption ............................................ 501Tubular Secretion .................................... 502Percentage of Reabsorption inEach Segment ........................................... 503
Classification of Diuretics ....................... 503Diuretics that Inhibit Transport in theProximal Convoluted Tubule ................. 505
Osmotic Diuretics .................................... 505Carbonic AnhydraseInhibitors (CAIs) ...................................... 506
Diuretics Acting on the Thick AscendingLoop of Henle (loop diuretics)/HighCeiling (most efficacious) Diuretics ...... 508
Mechanism of Action .............................. 508Effects on Electrolytes andRenal Blood Flow .................................... 508Pharmacokinetics .................................... 509Adverse Effects ........................................ 509Therapeutic Uses ..................................... 510Drug Interactions ..................................... 510
Diuretics that Inhibit Transport in theDistal Convoluted Tubule ...................... 510
Mechanism of Action .............................. 511Effects on Electrolytes andRenal Haemodynamics .......................... 511Pharmacokinetics .................................... 511Adverse Effects ........................................ 512Therapeutic Uses ..................................... 512Drug Interactions ..................................... 512
Diuretics that Inhibit Transport in theCortical Collecting Tubule ...................... 512
Na+ Channel Inhibitors ......................... 513Aldosterone Antagonists ........................ 513
Antidiuretic Drugs ................................... 516Introduction ............................................. 516Classification ........................................... 516Therapeutic Uses ..................................... 516
Vasopressin ............................................... 516References .................................................. 518
PART VII
DRUGS AFFECTING ENDOCRINE SYSTEM
Chapter - 32Pituitary HormonesAnterior Pituitary Hormones ................. 521
Growth Hormone..................................... 523Antagonists of Growth Hormone .......... 528Gonadorelin ............................................. 528Antagonists of Gonadorelin ................... 529Pituitary Hormones ................................. 529FSH and LH.............................................. 529Prolactin .................................................... 531
Posterior Pituitary Hormones ................ 533Antidiuretic Hormone ............................. 534Vasopressin Antagonists ........................ 536
Oxytocin ..................................................... 537Oxytocin Antagonist ............................... 538
References .................................................. 539
Chapter - 33Thyroid, Parathyroid Hormones andAntithyroid DrugsFunctional Anatomy of the Thyroid andParathyroid Glands .................................. 540Chemistry of Thyroid Hormones .......... 541
Biosynthesis of Thyroid Hormones ....... 542Regulation of Thyroid Function............. 544
Thyroid Hormone Receptors andMechanism of Action ............................... 545
Mechanisms of Action of T4 and T3 ....... 545Peripheral Metabolism ofThyroid Hormones .................................. 545Physiologic Effects ofThyroid Hormones .................................. 545Thyroid Disease States ............................ 547
Calcitonin ................................................... 547Physiological Effects of Calcitonin ........ 548
Contents (xxiii)
Control of Calcitonin Secretion .............. 548Disease States ........................................... 548
Parathyroid Hormone ............................. 548Physiological Effects ofParathyroid Hormone ............................. 548Control of ParathyroidHormone Secretion .................................. 549Disease States ........................................... 549Synthetic Thyroid Hormone ................... 550
Anti-Thyroid Drugs (ATDs) .................. 550Antithyroid Agents .................................. 550
Anion Inhibitors ....................................... 552Hormone Release Inhibitors ................... 552Drugs Destroying Thyroid Tissue ......... 552Miscellaneous Drugs............................... 552Thyroid Storm .......................................... 553Hyperthyroidism and Pregnancy .......... 553ATD Treatment DuringPregnancy and Lactation ........................ 553ATD Treatement ofHyperthyroidism in ........................................Children and Adolescents ...................... 554ATD Treatment before Thyroidectomy .. 554ATDs in Thyroid Storm ........................... 554ATDs in Amiodarone InducedThyrotoxicosis .......................................... 554
References .................................................. 555
Chapter - 34Insulin and Oral Hypoglycemic DrugsDiabetes Mellitus ...................................... 556
Classification of Diabetes Mellitus ........ 556What Happens to Bodies whenHyperglycemic? ....................................... 556Causes of Diabetes ................................... 557Pathophysiology ...................................... 557Diagnosis and Diagnostic Tests ............ 558
Complications of Diabetes ...................... 559Acute Complications of Diabetes ........... 559Chronic Complications of Diabetes ....... 560Microvascular (Microangiopathic)Disease ...................................................... 560Macrovascular Disease ........................... 563The Management of Diabetes ................. 564
Treatment of Diabetes ............................. 564Treatment for Patients withType 1 Diabetes ........................................ 564
Treatment for Patients withType 2 Diabetes ........................................ 564
Oral Hypoglycemics ................................. 565Sulfonylureas ........................................... 565
Meglitinide Analogues ............................ 568Insulin Sensitizers ................................... 568α-Glucosidase Inhibitors ........................ 572DPP-4 Inhibitors ..................................... 574
Incretin Therapy ....................................... 574Biosynthesis of Insulin ............................ 575
Insulins ....................................................... 575Structure of Insulin .................................. 575Insulin Secretion ...................................... 576Mechanism of Action .............................. 577Pharmacology of Insulin ......................... 578
Insulin Preparations ................................. 578Regular Insulin ........................................ 578NPH or Isophane Insulin ....................... 578Lente Insulin ............................................ 579Premixed Formulations ........................... 579Rapid Acting Analogues ........................ 579Long Acting Analogues .......................... 579Premixed Analogue Preparations .......... 579Selection of Insulin .................................. 579
References .................................................. 581
Chapter - 35Estrogens, Progestins and AndrogensEstrogens ................................................... 582
Biosynthesis ............................................. 583Effects ........................................................ 584Therapeutic Uses ..................................... 586Adverse Effects ......................................... 587
Anti Estrogens andEstrogenic Modulators ............................ 587
Inhibition of the Biosynthesis ofEstrogens .................................................. 587Inhibition of Estrogen Receptors, andSERM (Selective Estrogen ReceptorModulators) .............................................. 591Fulvestrant ................................................ 595
Progesterone and Progestins .................. 595Progesterone ............................................. 596Synthetic Progestins ................................ 597
Contents(xxiv)
Progesterone Antagonists ....................... 599Estroprogestative Combinations ............ 599
Androgens ................................................. 602Biosynthesis ............................................. 602Distribution .............................................. 602Biotransformations and Inactivation .... 603Sexual Effects ........................................... 603General Effects ......................................... 603Sexual Therapeutic Uses ......................... 604
Anti Androgens ........................................ 605Androgen Antagonists ............................ 605
References .................................................. 606
Chapter - 36Adrenal HormonesIntroduction .............................................. 607Adrenocorticosteroids ............................. 609
Glucocorticoids ........................................ 609Mineralocorticoids .................................. 612
Antagonists of Adrenocortical Agents . 613Synthesis Inhibitors andGlucocorticoid Antagonists ................... 613Mineralocorticoid Antagonists .............. 616
References .................................................. 616
PART VIIIDRUGS AFFECTING
RESPIRATORY SYSTEMS
Chapter - 37Drugs Used to Treat AsthmaIntroduction .............................................. 619
Asthma Triggers ...................................... 619Diagnostic Testing ................................... 619
Adrenoceptor Agonists ........................... 621Salmeterol ................................................. 621Albuterol ................................................... 622
Anticholinergics ........................................ 622Methylxanthines ....................................... 622Anti Inflammatory Agents ...................... 623
Corticosteroids ......................................... 624Mast Cell-Stabilizing Agents .................. 626Antileukotrienes ...................................... 627
References .................................................. 629
Chapter - 38Drugs Used to Treat Allergic RhinitisDefinition ................................................... 630Diagnosis .................................................... 630
Paediatrics ................................................ 630Testing....................................................... 630Treatment .................................................. 632
Pharmacological Therapy ........................ 633Intranasal Corticosteroids ...................... 633Oral Antihistamines ................................ 633Decongestants .......................................... 635Leukotriene Inhibitors ............................. 635Anticholinergics ...................................... 635Nasal Antihistamines ............................. 637Ocular Medications ................................. 637Nasal Saline ............................................. 637
Immunotherapy ........................................ 637Omalizumab (Xolair) ............................... 638Surgical Therapy ..................................... 639
References .................................................. 639
Chapter - 39Drugs Used to Treat Cough,COPD and Cystic FibrosisCough ......................................................... 640
Introduction.............................................. 640Treatment of Cough ................................. 642
Antitussives (CentralCough Suppressants) .............................. 642Expectorants ............................................. 643Antihistamines ........................................ 645Bronchodilators ....................................... 647
Relief of Nasal Congestion andOther Cold Symptoms ............................. 648
Sympathomimetic Drugs ........................ 648Pharyngeal Demulcents .......................... 649Traditional Cough andCold Remedies ......................................... 650Recommendations for Management of aSimple Cough or Cold or Sore Throat .... 650
COPD (Chronic ObstructivePulmonary Disease) ................................. 651
Pathophysiology ...................................... 651
Contents (xxv)
Chronic Bronchitis .................................. 653Emphysema .............................................. 654Etiology of COPD ..................................... 654Diagnosis of COPD.................................. 654Treatment of Chronic ObstructivePulmonary Disease.................................. 655Pharmacological Therapy of COPDExacerbations ........................................... 658
Cystic Fibrosis ........................................... 658Epidemiology and Etiology .................... 659Pathophysiology ...................................... 659Clinical Presentation and Diagnosis .... 661Laboratory Tests ...................................... 662Treatment .................................................. 662Nutrition ................................................... 663Future Direction of Therapy ................... 668
References .................................................. 668
PART IXDRUGS AFFECTING
GASTROINTESTINAL TRACT
Chapter - 40Drugs Used to Treat Peptic,Ulcer DiseaseClassification by Region/Location ........ 671Physiology of Acid Secretion ................. 672
Pathogenesis ............................................ 673Signs and Symptoms ............................... 674Complications .......................................... 674Differential Diagnosis ............................. 674
Treatment .................................................. 674Neutralization of Gastric Acid/Antacids ..................................................... 675Reduction of Gastric Acid ....................... 676
H2-Receptor Antagonists ........................ 676Proton Pump Inhibitors (PPIs) ............... 678Prostaglandin Analogues ....................... 680Mucosal Protective Agents ..................... 682
Sucralfate .................................................... 682Colloidal Bismuth Compounds ............. 683Surgery ...................................................... 684
References .................................................. 684
Chapter - 41Drugs Used in ConstipationIntroduction .............................................. 686Causes ......................................................... 686
Primary ..................................................... 686Diet ............................................................ 686Medication ................................................ 686Metabolic and Muscular ......................... 686Structural and FunctionalAbnormalities ........................................... 686Drugs Associated with Constipation .... 686
Treatment .................................................. 687Non Pharmacological Measures ............ 687Drugs Available toTreat Constipation ................................... 688Bulk-Forming Laxatives .......................... 689Osmotic Laxatives ................................... 689Stimulant Laxatives ................................. 689
Other Drugs .............................................. 691Novel agents ............................................. 691Serotonin 5-HT4-Receptor Agonists ....... 691
References .................................................. 692
Chapter - 42Emetics and Antiemetic DrugsEmesis (Vomiting) .................................... 693
Control of Vomiting ................................. 693Causes ....................................................... 694
Emetics ....................................................... 695Emetic Drugs ............................................. 695
Apomorphine ........................................... 695Ipecacuanha ............................................. 695
Antiemetics ................................................ 696Introduction.............................................. 696Classification - Antiemetic Drugs .......... 696
H1 Antihistamines andMuscarinic Antagonists ........................... 696
Selective 5-HT3 Antagonists ................... 697D2 Antagonists .......................................... 697
Substituted Benzamides ......................... 697Phenothiazines ........................................ 699Butyrophenones ....................................... 699
Cannabinoids (Dronabinol, Nabilone) . 699Dronabinol ............................................... 699Nabilone ................................................... 699
Contents(xxvi)
Glucocorticoids ......................................... 699Dexamethasone, Methylprednisolone .. 699
Benzodiazepines ....................................... 700Diazepam, Lorazepam ............................ 700
Neurokinin-1 (NK1) Antagonists ........... 700Aprepitant, Fosaprepitant ...................... 700Therapeutic Uses of Antiemetics ........... 701
References .................................................. 702
Chapter - 43Drugs Used in DiarrhoeaIntroduction .............................................. 703Types of Diarrhoea .................................. 703
Secretory Diarrhoea ................................. 703Osmotic Diarrhoea .................................. 703Exudative Diarrhoea ............................... 703Motility Related Diarrhoea ..................... 703Inflammatory Diarrhoea ......................... 704Dysentery .................................................. 704
Differential Diagnosis .............................. 704Infections .................................................. 704Malabsorption .......................................... 704Irritable Bowel Syndrome ....................... 705
Treatment .................................................. 705Oral Rehydration Therapy .................... 706
Antimotility and Antisecretory Agents 706Opioids ..................................................... 706α2 Adrenergic Receptor Agonists ........... 708Octreotide and Somatostatin .................. 708
Absorbent Agents .................................... 708Bulk-Forming andHydroscopic Agents ................................ 708Bile Acid Sequestrants ............................ 709Bismuth ..................................................... 710Other Agents ............................................ 710Alternative Therapies .............................. 710
References .................................................. 714
Chapter - 44Digestants and GERDDigestants .................................................. 715
Examples of Digestants ........................... 715Digestants in Gastric Dysfunction ........ 716Digestants in Pancreatic Insufficiency .. 716
GERD .......................................................... 716Pathophysiology ...................................... 716Signs and Symptoms ............................... 717Diagnosis .................................................. 717Treatment .................................................. 718Antacids and Antacid-AlginicAcid Products ........................................... 718H2-Receptor Antagonists (H2RAs) ......... 719Proton Pump Inhibitors (PPIs) ............... 719Promotility Agents ................................... 720
References .................................................. 720
PART X
DRUGS USED FOR OTHER THERAPIES
Chapter - 45Drugs Used toTreat Erectile DysfunctionIntroduction .............................................. 723
Physiology of Erection ............................ 723Clinical Features ...................................... 724Causes of ED ............................................ 724Diagnosis .................................................. 724
Treatment .................................................. 725Drug Therapy ........................................... 725
Hypogonadism and Testosterone ......... 729Replacement Therapy ............................. 729Vacuum Constriction Device .................. 729Surgery ...................................................... 729Injectable Medications ............................ 730Psychotherapy ......................................... 732Nonpharmacological Treatment ............ 732
References .................................................. 733
Chapter - 46Drugs Used to Treat OsteoporosisIntroduction .............................................. 734How Bones Work ..................................... 734
Signs .......................................................... 734Risk Factors .............................................. 734Tests .......................................................... 735
Treatment .................................................. 735Bisphosphonates ..................................... 735
Contents (xxvii)
Raloxifene ................................................. 736Calcitonin ................................................. 736Teriparatide .............................................. 737Denosumab .............................................. 737Estrogen/Hormone Therapy .................. 737Using Osteoporosis Therapies inCombination ............................................. 738New Treatments Coming up .................. 741
References .................................................. 741
Chapter - 47Drugs Used to Treat ObesityDefinition ................................................... 742Etiology ...................................................... 742Health Effects of Obesity ........................ 742
Diabetes (Type 2) ..................................... 743Hypertension ........................................... 743Cardiovascular Disease (CVD) .............. 743Stroke ......................................................... 743Osteoarthritis (OA) .................................. 743Sleep Apnea.............................................. 743Investigations ........................................... 744
Treatment of Obesity ............................... 744Behavior Modification ............................ 744Pharmacotherapy .................................... 745
Lorcaserin .................................................. 747Other Appetite Suppressants ................. 748Surgical Intervention ............................... 748
References .................................................. 750
PART XIBIOGENIC AMINES AND POLYPEPTIDES
Chapter - 48Histamine and AntihistaminesIntroduction .............................................. 753
Chemistry and Pharmacokinetics .......... 753Release ...................................................... 754
Types of HistamineReceptors .................................................... 754
Mechanism of Action .............................. 755Conditions that Release Histamine ....... 755Tissue and Organ SystemEffects of Histamine ................................. 756
Nervous System ....................................... 756
Cardiovascular System ........................... 756Bronchiolar Smooth Muscle ................... 756Gastrointestinal Tract Smooth Muscle .. 756Other Smooth Muscle Organs ................ 756Secretory Tissue ....................................... 756Metabolic Effects ...................................... 757Triple Response ....................................... 757Clinical Uses ............................................ 757Toxicity and Contraindications ............. 757
Histamine Antagonists ............................ 757Basic Pharmacology ofH1-Receptor Antagonists ........................ 757
H2 Receptor Antagonists ......................... 762H3 Receptor Drugs ................................... 763H4 Receptor Antagonists ......................... 763
Inhibitors of Histamine Release ............. 763References .................................................. 764
Chapter - 495-Hydroxytryptamine, itsAgonists and AntagonistsIntroduction .............................................. 765
Distribution (PNS) ................................... 765Synthesis and Metabolism ...................... 765
Carrier Mediated Uptake ....................... 765Drugs Affecting onTryptaminergic System .......................... 765Mechanisms of Action ............................ 766
Tissue and Organ System Effects .......... 770Nervous System ....................................... 770Respiratory System .................................. 771Cardiovascular System ........................... 771Gastrointestinal Tract ............................. 771Other Systems........................................... 771Serotonin Syndrome ................................ 771
Serotenergic Drugs ................................... 772Serotonin Agonists .................................. 772Serotonin Antagonists ............................ 774
Migraine ..................................................... 775General Treatment Principles ................ 776Nonspecific Acute Treatment ................. 776
Neuroleptics/Antiemetics ....................... 777Specific Acute Treatment-Triptans ........ 778
Contents(xxviii)
Specific Migraine Preventive Agents ..... 779Other Preventive Agents ......................... 781
References .................................................. 782
Chapter - 50Angiotensin, Kinins, Leukotrienes,Prostaglandins, Cytokines,Nitric Oxide and Platelet activatingFactor AngiotensinAngiotensin ............................................... 783Angiotensinogen ...................................... 783
Angiotensin I ........................................... 783Angiotensin II .......................................... 783Angiotensin III ......................................... 784Angiotensin IV ......................................... 784Effects ........................................................ 784Angiotensin Receptors andMechanism of Action .............................. 785
Drugs Acting on ReninAngiotensin Aldosterone System .......... 786
ACE Inhibitors ......................................... 786Angiotensin II Receptor Antagonists .... 792Renin Inhibitors ....................................... 794
Types of Kinins ......................................... 796Kallikrein-Kinin System .......................... 796Kallikreins ................................................ 796Effects of Kinins ....................................... 796
Leukotrienes .............................................. 798History and Name ................................... 798Control and Regulation .......................... 798Enzymatic Control ................................... 800Types ......................................................... 801Functions of Leukotrienes ...................... 801Leukotrienes in Asthma .......................... 802Types of Anti-leukotriene Drugs ............ 802
Prostaglandins........................................... 803History and Name ................................... 803Types of PGs ............................................. 804
Biosynthetic Pathways ............................. 804PG Receptors ............................................ 805Cyclooxygenases ..................................... 806Functions .................................................. 807Role in Pharmacology ............................. 809Effects of Aspirin andother Pain Killers ..................................... 809Non-steroidal Anti-inflammatoryDrugs (NSAIDs) ....................................... 810
Cytokines ................................................... 810Properties of Cytokines ........................... 810Classification of Cytokines ..................... 811Cytokine Receptors .................................. 814Function of Cytokines ............................. 814
Nitric Oxide ............................................... 815Introduction .............................................. 815
The Structure and Nature ofNitric Oxide .............................................. 815
Synthesis of Nitric Oxide ........................ 815Activation of NOS .................................... 816
Role of Nitric Oxide in theHuman Body ............................................ 817
Platelet Activating Factor ........................ 822Chemistry and Biology............................ 822
Biosynthesis ............................................... 823Biochemical Function .............................. 823
Pharmacological Properties .................... 825Mechanism of Action of PAF .................. 825Physiological andPathological Functions of PAF ............... 825
Role in Pharmacology .............................. 826References .................................................. 826
PART XIICHEMOTHERAPEUTIC DRUGS
Chapter - 51Sulfonamides, Trimethoprim andCotrimoxazoleSulfonamides ............................................. 831
Antibacterial Spectrum ........................... 833Classification ............................................. 833
General Properties ................................... 833Metabolism and Excretion ...................... 836Trimethoprim–Sulfamethoxazole........... 838Gastrointestinal Infections ...................... 840Respiratory Infections ............................. 842References .................................................. 844
Chapter - 52Cell Wall InhibitorsClassification of Agents Affecting CellWall Synthesis ........................................... 845β-Lactam Antibiotics ................................ 846
Contents (xxix)
Penicillin’s .................................................. 848General Properties ................................... 848Classification ........................................... 848Penicillins ................................................. 848Mechanisms of Resistance...................... 850
Natural Penicillins .................................... 851Antistaphylococcal(Penicillinase-Resistant) Penicillins ........ 851Aminopenicillins ....................................... 852
Antipseudomonal Penicillins ................ 852Cephalosporins ......................................... 855Classification ............................................. 855
Antimicrobial Activity ............................ 857Pharmacokinetic Features ...................... 858Clinical Uses ............................................ 858
Monobactams ............................................ 860β-lactamase Inhibitors (Clavulanic Acid,Sulbactam and Tazobactam) ................... 860β-Lactamase Inhibitors ................................. 860β-Lactamase Inhibitors in Clinical Practice 861Carbapenems ............................................. 864Other Cell Wall Synthesis Inhibitors ..... 865
Vancomycin and Teicoplanin ................ 865Bacitracin .................................................. 866
References .................................................. 867
Chapter - 53Protein Synthesis InhibitorsAminoglycosides ...................................... 868
Classification ........................................... 868Microbial Resistance ................................. 870Kinetics ....................................................... 871
Toxicity ..................................................... 872Drug Interactions ..................................... 872Heparin ...................................................... 872Individual Agents ..................................... 872
Streptomycin ............................................ 872Gentamicin ............................................... 873Tobramycin .............................................. 873Amikacin .................................................. 873Netilmicin ................................................. 873Kanamycin and Neomycin ..................... 873Spectinomycin .......................................... 873
Tetracyclines .............................................. 874Classification ........................................... 874Origin ........................................................ 874
Chloramphenicol ....................................... 878Macrolides ................................................. 879Clindamycin/Lincomycin ........................ 883Streptogramins .......................................... 884
Quinupristin-Dalfopristin(Synercid) .................................................. 884
References .................................................. 885
Chapter - 54Quinolones and Urinary AntisepticsQuinolones ................................................. 886
Introduction.............................................. 886Resistance to Quinolones ....................... 890
Therapeutic Uses of Quinolones ............ 890Genitourinary Infections ......................... 890
Prostatitis ................................................... 891Respiratory Diseases ................................ 891Sexually Transmitted Diseases ............... 892Gastroenteritis .......................................... 892Skin and Soft Tissue Infections .............. 893Urinary Antiseptics .................................. 895
Methenamine ........................................... 895Nitrofurans (Nitrofurantoin) ................. 895
Fosfomycin ................................................ 897References .................................................. 897
Chapter - 55AntimycobacterialsTuberculosis .............................................. 898
Transmission ........................................... 898Signs and Symptoms ............................... 898Cause ......................................................... 898Drugs {Multiple Drug Therapy} ............. 899
Isoniazid ..................................................... 901Rifampicin .................................................. 902Ethambutol ................................................ 903Pyrazinamide ............................................ 903Streptomycin ............................................. 904Cycloserine ................................................ 904
DOTS ......................................................... 905Prevention................................................. 905
Contents(xxx)
Leprosy ...................................................... 905Introduction.............................................. 905Classification Schemes for Leprosy ....... 906
Tuberculoid/Paucibacillary .................... 907Lepromatous/Multibacillary ................. 907Physical Findings inLepromatous Disease .............................. 907Borderline (Dimorphous) ........................ 908Indeterminate Leprosy ............................ 908
Bone Changes in Leprosy ....................... 908Transmission of Leprosy ........................ 908Diagnostic Tests ....................................... 908
Histological Testing ................................. 909Clofazamine ............................................... 910Dapsone...................................................... 911
MDT Side-Effects ..................................... 911Complications of Medical Therapy ....... 911Surgical Treatments ................................. 911
References .................................................. 912
Chapter - 56Antifungal DrugsIntroduction .............................................. 913
Types of Fungal Infections - Mycoses .... 913Classification of Antifungals .................. 914Azole Antifungals forSystemic Infections ................................... 914
Azoles – Mechanism ............................... 915Ketoconazole ............................................. 915Fluconazole ................................................ 917Itraconazole ............................................... 918Voriconazole .............................................. 918Posaconazole ............................................. 918Amphotericin B ......................................... 918Flucytosine ................................................. 920Squalene Epoxidase Inhibitors ............... 921
Terbinafine ............................................... 921Griseofulvin ............................................... 922Nystatin ...................................................... 922Ciclopirox ................................................... 922Tolnaftate ................................................... 923
Cell Wall Inhibitors ................................. 923Spectrum ................................................... 923
Undecylenic Acid ..................................... 924References .................................................. 925
Chapter - 57Antiprotozoal DrugsProtozoal Infections ................................. 926Malaria ........................................................ 926
Cause ......................................................... 926Parasite Life Cycle ................................... 926Classification of Anti Malarial Drugsaccording to Site of Action ...................... 927
Chloroquine ............................................... 928Amodiaquine ............................................. 929Piperaquine ................................................ 930Artemisinin (Qinghaosu)and its Derivatives ................................... 930Quinine and Quinidine ............................ 931Mefloquine ................................................. 932Primaquine ................................................. 932Atovaquone ............................................... 933Pyrimethamine .......................................... 934Proguanil: Chloroguanide ....................... 935Antibiotics .................................................. 935
Doxycycline .............................................. 935Halofantrine and Lumefantrine ............. 936
Combination Therapy forChloroquine Resistant Malaria .............. 937Treatment of ComplicatedP. falciparum ............................................ 937
Anti-Amoebic Drugs ................................ 937Life Cycle of E. histolytica ....................... 937
Therapeutic Classification ofAnti-Amoebic Drugs ................................ 938Metronidazole (Flagyl) ............................ 938Tinidazole .................................................. 940Emetines ..................................................... 940Chloroquine ............................................... 941Diloxanide Furoate(Luminal Amebicide) ............................... 941Iodoquinol ................................................. 942Antibiotics .................................................. 942
Paromomycin Sulphate ........................... 942Tetracyclines ............................................ 943Treatment of SpecificForms of Amebiasis ................................. 943
Chemotherapy for Trypanosomiasis ..... 943Treatment .................................................. 943
Contents (xxxi)
Melarsoprol .............................................. 943Pentamidine Isethionate ......................... 944
Nifurtimox ................................................. 945Suramin ...................................................... 945Benznidazole ............................................. 946Chemotherapy for Leishmaniasis .......... 946
Life Cycle of the CausativeOrganism: Leishmania Species .............. 946Treatment .................................................. 946
Chemotherapy for Toxoplasmosis ......... 947Chemotherapy for Giardiasis ................. 947
References .................................................. 947
Chapter - 58Anthelmintic DrugsHelmintic Infections ................................. 948
Types of Worms ....................................... 948Intestinal Worms ..................................... 948
Anthelmintic Drugs .................................. 948Classification ........................................... 949Piperazine................................................. 949Albendazole ............................................. 950Benzimidazoles ........................................ 950Mebendazole ............................................ 951Thiabendazole ......................................... 951Diethylcarbamazine ................................ 952Niclosamide ............................................. 952Ivermectin ................................................. 953Suramin .................................................... 954Pyrantel Pamoate ..................................... 955Paraherquamide ...................................... 956Praziquantel ............................................. 956Oxamniquine ........................................... 957Bithionol ................................................... 957Metrifonate ............................................... 957Emodepside .............................................. 958Nitazoxanide ........................................... 959
References .................................................. 959
Chapter - 59Antiviral DrugsIntroduction .............................................. 960
Research in Antiviral Chemotherapy.... 960Antiviral Agents ...................................... 960
Antiviral Drugs: General Features ......... 963Amantadine and Congeners .................. 963
Ribavirin ..................................................... 965Acyclovir and Congeners ........................ 966Vidarabine ................................................. 968Idoxuridine and Trifluridine .................. 969
Idoxuridine ............................................... 969Trifluridine ............................................... 969
Foscarnet .................................................... 970Zidovudine ................................................ 971Deoxynucleosides used in AIDS ............ 972
Stavudine .................................................. 972Didanosine ............................................... 972Lamivudine .............................................. 973Abacavir .................................................... 973Zalcitabine ................................................ 973HIV Protease Inhibitors ........................... 974Saquinavir ................................................ 974Ritonavir ................................................... 974Indinavir ................................................... 975Nelfinavir ................................................. 975Amprenavir .............................................. 975Lopinavir–Ritonavir ............................... 975Entry Inhibitors ........................................ 975Interferon’s ............................................... 975
References .................................................. 976
Chapter - 60Anticancer DrugsIntroduction .............................................. 977Cell Cycle Specific Agents andCell Cycle Non Specific Agents .............. 978Mechanism of Anticancer Drugs ............ 978Classification of Anticancer Drugs ........ 978Nitrogen Mustards ................................... 983
Mechlorethamine ..................................... 983Cyclophosphamide ................................... 983Ifosfamide .................................................. 984Chlorambucil ............................................. 985Nitrosoureas .............................................. 985Streptozocin ............................................... 985Alkyl Sulfonates ........................................ 986
Busulfan.................................................... 986
Contents(xxxii)
Ethylenimines ............................................ 986Thiotepa .................................................... 986
Triazenes .................................................... 986Dacarbazine ............................................. 986
Antimetabolites ......................................... 987Folate Antagonists ................................... 987Methotrexate ............................................. 990Gemcitabine.............................................. 991
Purine Analogues ..................................... 991Thioguanine (6-Thioguanine) ................ 991Mercaptopurine (6-Mercaptopurine) .... 992Fludarabine .............................................. 992Pentostatin ................................................ 992Cladribine ................................................. 993
Pyrimidine Analogues ............................. 993Cytarabine ................................................ 993Fluorouracil .............................................. 993
Antibiotics .................................................. 994Doxorubicin and Daunorubicin ............ 995
Idarubicin ................................................... 996Bleomycin ................................................. 996Mitomycin................................................. 996Dactinomycin ........................................... 997Plicamycin ................................................ 997Plant-Derived Products ........................... 997Vinca Alkaloids ..................................... 1000
Epipodophyllotoxins .............................. 1001Etoposide ................................................ 1001Teniposide .............................................. 1001
Taxanes ..................................................... 1001Paclitaxel ................................................ 1001
Enzymes ................................................... 1002L-Asparaginase ...................................... 1002
Hormone Derivatives ............................ 1002Tamoxifen ............................................... 1002
Estramustine ............................................ 1003Flutamide ................................................. 1003Buserelin and Leuprolide ...................... 1004Somatostatin Analogue.......................... 1004Miscellaneous Agents ............................ 1004
Hydroxyurea .......................................... 1004Procarbazine ............................................ 1005Mitotane ................................................... 1005
Hexamethylmelamine ............................ 1005Cisplatin ................................................. 1006
Carboplatin .............................................. 1006Mitoxantrone ........................................... 1006Immunomodulating Agents .................. 1007
Levamisole .............................................. 1007Interferon Alfa-2b................................... 1007
Interleukins .............................................. 1007Aldesleukin ............................................ 1007
Cellular Growth Factors ........................ 1007Filgrastim ................................................ 1007
Sargramostim .......................................... 1008New Drug Therapies for Cancer ......... 1008
Imantinib ................................................ 1008Herceptin ................................................ 1008Iressa ....................................................... 1008
References ................................................ 1009
PART XIIIDRUGS USED IN SKIN AND EYE
DISORDERS
Chapter - 61Antiseptics and DisinfectantsPeroxygens .............................................. 1023References ................................................ 1026
Chapter - 62Drugs Used to Treat GlaucomaDefinition ................................................. 1027
Etiology ................................................... 1027Pathophysiology ..................................... 1027Clinical Features ..................................... 1028
Open Angle Glaucoma.......................... 1028Drugs that may Induce or PotentiateIncreased Intraocular Pressure ............ 1028
Diagnosis .................................................. 1029Classification of Drugsused in Glaucoma ................................. 1029
Treatment of Ocular Hypertension OpenandAngle Glaucoma ............................... 1029Treatment of Closed-AngleGlaucoma ................................................. 1030References ................................................ 1032
Contents (xxxiii)
Chapter - 63Drugs Used to Treat Psoriasis andAcne VulgarisPsoriasis .................................................... 1033
Causes and Risk Factors ....................... 1033Symptoms ............................................... 1033Classification ......................................... 1033Nonpustular ........................................... 1034Pustular .................................................. 1034Other ........................................................ 1034Diagnosis ................................................ 1034
Treatment ................................................ 1035Nonpharmacological Therapy ............. 1035Emollients (Moisturizers) ..................... 1035Balneotherapy (and Climatotherapy) .. 1035
First-Line Topical Pharmacotherapy ... 1035Keratolytics ............................................. 1035
Corticosteroids ....................................... 1035Topical Corticosteroids ......................... 1035Vitamin D Analogues ............................ 1036Calcipotriene .......................................... 1036
Tazarotene ............................................... 1036Tazarotene (Tazorac) ............................. 1036
Second-Line TopicalPharmacotherapy .................................... 1037
Coal Tar .................................................. 1037Anthralin ................................................ 1037
First-Line SystemicPharmacotherapy .................................... 1037
Infliximab ............................................... 1037Etanercept ............................................... 1038Adalimumab .......................................... 1038Alefacept ................................................. 1038Efalizumab ............................................. 1038
Second-Line SystemicPharmacotherapy .................................... 1039
Acitretin .................................................. 1039Cyclosporine .......................................... 1039Tacrolimus .............................................. 1039Methotrexate ........................................... 1039
Mycophenolate Mofetil .......................... 1040Sulfasalazine .......................................... 1040
Phototherapy andPhotochemotherapy ............................... 1041
Hydroxyurea .......................................... 1041Acne Vulgaris ......................................... 1042Nonpharmacological Therapy ............. 1042
Topical Pharmacotherapy...................... 1043Benzoyl Peroxide ................................... 1043Tretinoin ................................................. 1043Adapalene .............................................. 1043Tazarotene .............................................. 1044Erythromycin ......................................... 1044Clindamycin ........................................... 1044Azelaic Acid ........................................... 1044Salicylic Acid, Sulfur and Resorcinol .. 1044
Systemic Pharmacotherapy ................... 1044Isotretinoin ............................................. 1044Oral Antibacterial Agents ..................... 1045Oral Contraceptives ............................... 1045
References ................................................ 1046
PART XIVTOXICOLOGY
Chapter - 64Introduction to ToxicologyManifestations of Toxicity .................... 1049
Organ Toxicity ....................................... 1049Pulmonary Toxicity ............................... 1049Hepatotoxicity ........................................ 1050Nephrotoxicity ....................................... 1051Neurotoxicity ......................................... 1051Immunotoxicity ...................................... 1051
Insecticides .............................................. 1054Herbicides and Rodenticides ............... 1054
References ................................................ 1055
Chapter - 65Heavy Metal Intoxication and ChelatorsDefinitions ............................................... 1056Heavy Metal ............................................ 1056Lead .......................................................... 1056Arsenic ...................................................... 1058Cadmium.................................................. 1059Mercury .................................................... 1061
Contents(xxxiv)
Chelating Agents .................................... 1061Introduction............................................ 1061Characteristics of an Ideal Chelator .... 1062
Common Chelating Agents:Pharmacology and Toxicology ............. 1062
Calcium Disodium EthylenediamineTetraacetic Acid (CaNa2EDTA) ............ 1062Calcium Trisodium DTPA .................... 1064D-Penicillamine ..................................... 1065British Anti Lewisite (BAL) .................. 1065Meso-2,3-DimercaptosuccinicAcid (DMSA) .......................................... 1066Sodium 2,3 Dimercaptopropane-l-Sulphonate (DMPS) ............................... 1067New DMSA Analogues ......................... 1067Monoisoamyl DMSA (MiADMSA) ...... 1068Monomethyl DMSA (MmDMSA) andMonocyclohexyl DMSA (MchDMSA) . 1068Deferoxamine (DFO) .............................. 1069Deferiprone (L1) ..................................... 1069TETA ....................................................... 1070Nitrilotriacetic Acid (NTA) ................... 1070
References ................................................ 1071
PART XVMiscellaneous
Chapter - 66Management of the Poisoned PatientIntroduction ............................................ 1075
Clinical Evaluation................................ 1075General Management ............................. 1077Diagnostic Adjuncts ............................... 1078Gastrointestinal Decontamination ....... 1079
Disposition ............................................. 1080A General Approach to theTreatment of Acute Poisoning .............. 1081
References ................................................ 1082
Chapter - 67Drugs Used toTreat Rheumatoid Arthritis and GoutRheumatoid Arthritis (RA) ................... 1083Pathogenesis ............................................ 1083Signs and Symptoms .............................. 1085
Diagnosis .................................................. 1085Treatment ................................................ 1085Disease ModifyingAntirheumatic Drugs ............................. 1085
Methotrexate ........................................... 1085Basic Pharmacology .............................. 1086
Sulfasalazine ............................................ 1086Antimalarials ......................................... 1087Leflunomide ........................................... 1088Etanercept ............................................... 1089Interleukin-1 Antagonists ..................... 1090Gold Compounds .................................. 1091
Azathioprine ............................................ 1092Cyclosporine ............................................ 1092Cyclophosphamide ................................. 1093Minocycline .............................................. 1093
Penicillamine ......................................... 1094Combination Therapy ........................... 1094
Gout .......................................................... 1094Causes ..................................................... 1095Drugs that causes Hyperuricemia ....... 1095Treatment ................................................ 1095
NSAIDs .................................................... 1095Colchicine ................................................. 1095Drug Interactions ................................... 1096
Corticosteroids ....................................... 1096Uricosurics Drugs .................................. 1097
Probenecid ............................................... 1097Sulfinpyrazone ........................................ 1098Allopurinol .............................................. 1099References ................................................ 1101
Chapter - 68Drugs that Affect Uterine FunctionPreterm Birth .......................................... 1102Uterine Stimulants (Oxytocics) ............ 1102Oxytocin (Syntocinon) ........................... 1103
Synthesis ................................................. 1103Ergot Alkaloids ...................................... 1104Prostaglandins (PGE2 & PGF2a) ........... 1105
Uterine Relaxants ................................... 1107Ethanol .................................................... 1107β2 Adrenoceptor Agonists ..................... 1107
Contents (xxxv)
Terbutaline ............................................. 1108Magnesium Sulfate ................................ 1108Other Agents .......................................... 1108
Drugs Used toPromote Cervical Ripening ................... 1109References ................................................ 1109
Chapter - 69Immunosuppressants andImmunostimulantsIntroduction ............................................ 1110
Cell-mediated Immunity ....................... 1110Humoral Immunity................................ 1111
Immunosuppressant Drugs ................... 1111Cyclosporine .......................................... 1112
Tacrolimus (Fk506) ................................. 1113Differences between CsA and TAC .... 1114
Corticosteroids ....................................... 1115Azathioprine .......................................... 1117Mycophenolate Mofetil ......................... 1117Leflunomide ........................................... 1119Methotrexate ........................................... 1119
Antilymphocyte Globulins (ALG) andAntithymocyte Globulins (ATG) ......... 1119Muromonab-CD3 .................................... 1119Rho (D) Immune Globulin ...................... 1121Basiliximab and Daclizumab ................. 1121Infliximab ................................................. 1121Omalizumab ............................................ 1121Interferons ............................................... 1121Thalidomide ............................................ 1122Immunostimulants .................................. 1123
Bacillus Calmette-Guérin ...................... 1123Levamisole .............................................. 1124
Thymic Factors ........................................ 1124Cytokines ................................................. 1124Myeloid Colony–Stimulating Factors . 1125Other Cytokines ..................................... 1125References ................................................ 1125
Chapter - 70Vitamins, Minerals and AntioxidantsIntroduction ............................................ 1126
Classification ......................................... 1127Fat Soluble Vitamins ............................. 1127
Vitamin A (precursor –beta carotene) ......................................... 1128
Vitamin D ............................................... 1130Vitamin E ................................................ 1130Vitamin K ................................................ 1131
Water Soluble Vitamins ......................... 1131Vitamin B1 ............................................... 1133Vitamin B2 ................................................ 1133Vitamin B3 ................................................ 1134Vitamin B5 ................................................ 1134VitaminB6 ................................................. 1134Vitamin B7 ................................................ 1135Vitamin B9 ................................................ 1136
Biochemistry of DNABase and Amino Acid Production ....... 1136Conversion to Biologically .................... 1136Active Derivatives .................................. 1136
Vitamin B12 ............................................... 1137Vitamin C ................................................. 1137Minerals .................................................... 1139
Major and Trace Minerals .................... 1140Uses of Minerals .................................... 1140Major Minerals ....................................... 1140Trace Minerals ....................................... 1142Antioxidants .......................................... 1145Mechanisms of Metals inAccelerating Lipid Oxidation .............. 1145Factors Affecting theEfficiency of Antioxidants .................... 1147Choices of Antioxidants ....................... 1147
References ................................................ 1149
Chapter - 71Drug Therapy in PregnancyPharmacokinetics .................................... 1151
Lipid Solubility ...................................... 1151Molecular Size ........................................ 1151Placental Transporters .......................... 1151Protein Binding ...................................... 1152Placental and Fetal Drug Metabolism . 1152
Pharmacodynamics ................................. 1152Maternal Drug Actions ......................... 1152Therapeutic Drug Actionsin the Fetus ............................................. 1153
Contents(xxxvi)
Predictable Toxic DrugActions in the Fetus ............................... 1153Teratogenic Drug Actions ..................... 1153Teratogenic Mechanisms ...................... 1153
Defining a Teratogen ............................. 1155FDA Pregnancy Categories .................. 1157References ................................................ 1163
Chapter - 72Drugs Use during LactationLactation .................................................. 1164References ................................................ 1168
PART XVIPHARMACOLOGY GATE ANDGPAT PREVIOUS QUESTIONS
Chapter - 73Multiple Choice, Linked and Match theFollowing Questions of Previous GATEand GPAT Examinations along withAnswersMultiple Choice Questions .................... 1171
Two Options Correct Questions........... 1181Data Based Questions ........................... 1184Several Drugs are used for Migraine ... 1185Statement for LinkedAnswer Questions ................................. 1185Match the Pairs ...................................... 1187
APPENDIXES
Appendix - 1Gene TherapyIntroduction ............................................ 1195
Principles of Gene Therapy .................. 1195How does Gene Therapy Work? .......... 1195What Gene Therapy can Achieve ........ 1196Types ....................................................... 1199Methods of Gene Delivery .................... 1199Various Strategies for Gene Therapy ... 1199
Gene Therapy Vectors ........................... 1200Viruses .................................................... 1200Retroviruses ............................................ 1200Adenoviruses ......................................... 1200
Adeno Associated Viruses .................... 1201Envelope Protein Pseudotyping ofViral Vectors ........................................... 1201Replication Vectors ................................ 1202Cis and Trans Acting Elements ........... 1202Herpes Simplex Virus ........................... 1202Naked DNA............................................ 1202Oligonucleotides .................................... 1202Lipoplexes and Polyplexes ................... 1203Hybrid Methods ..................................... 1204Dendrimers ............................................. 1204What is the Current Status ofGene Therapy Research? ...................... 1204
References ................................................ 1206
Appendix 2Drug Discovery and DevelopmentIntroduction ............................................ 1207The Discovery Process ........................... 1207
Pre Discovery ......................................... 1207Target Identification .............................. 1207Target Prioritization/Validation ........ 1207Lead Identification ................................ 1208Lead Optimization ................................ 1208Early Safety Tests ................................... 1208Lead Optimization ................................ 1208Preclinical Testing ................................. 1209
The Development Process ..................... 1209Clinical Trial Design ............................... 1209
Phase 1 Clinical Trial ............................ 1210Phase 2 Clinical Trial ............................ 1210Phase 3 Clinical Trial ............................ 1210
New Drug Application (NDA) andApproval .................................................. 1210
Submit Application forApproval to FDA ................................... 1210Benefit Vs. Risk ...................................... 1211Manufacturing ....................................... 1211Ongoing Studies and Phase 4 Trials ... 1211Conclusion ............................................. 1214
References ................................................ 1214
Appendix - 3Abnormal Actions of DrugsAdverse Drug Event .............................. 1215The Risk to Benefit Ratio ...................... 1215
Contents (xxxvii)
Classification ........................................... 1216Predictable Reactions (Type A) ............ 1216
Seriousness and Severity ....................... 1216Unpredictable Reactions (Type B) ....... 1216
Overall Drug Risk ................................... 1217Location.................................................... 1217Mechanisms ............................................. 1217Abnormal Pharmacokinetics ................. 1217Detecting Adverse Effects .................... 1219Prevention of AdverseDrug Reactions ........................................ 1219Hypersensitivity ..................................... 1219Drug Habitation ..................................... 1223Drug Allergy ........................................... 1223References ................................................ 1226
Appendix - 4Classifications of MedicationsIntroduction ............................................ 1227Medication Classifications .................... 1227Drug Classification ................................. 1240
Appendix - 5Drug InteractionsDefinition ................................................. 1270
Prevalence............................................... 1270Factors Contributing toDrug Interactions ................................... 1270Mechanisms of Drug Interaction ......... 1271
Drug Distribution Interactions ............ 1273Protein-binding Interactions ................ 1273Drug Excretion Interactions ................. 1275Drug Food Interactions ......................... 1285
Reducing the Risk of Drug Interactions –Principles of DrugInteractions Management ...................... 1290References ................................................ 1291
Index ......................................................... 1293