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