Clinical Pharmacology in Obstetrics (eBook)

Front Cover 1
Clinical Pharmacology in Obstetrics 4
Copyright Page 5
Table of Contents 10
PREFACE 6
LIST OF CONTRIBUTORS 8
FOREWORD 12
Chapter 1. Drug usage in pregnancy 14
Drugs Used in Pregnancy 14
New Drug Treatments in Obstetrics 15
Clinical Pharmacological Research in Obstetrics 16
References 17
Chapter 2. Pharmacokinetics in pregnancy 18
Elimination of Drugs 18
Single-compartment Model and First-order Elimination 19
Apparent Volume of Distribution 19
The Two-compartment Model 21
Changes in Pharmacokinetic Parameters in Pregnancy 23
Influence of the Fetus and Placenta 26
Conclusion 26
References 26
Chapter 3. Adverse effects of drugs on the fetus 30
Introduction 30
Acute Pharmacological Effects on the Fetus 30
Structural Teratogenicity 31
Behavioural Teratogenicity 33
Enzyme Induction 35
Predictability of Animal Tests for Teratogenicity 36
False and Negative Animal Tests 36
False Positive Animal Tests 36
Why are Animal Tests Inaccurate? 37
Future Teratogenicity Tests 37
Teratogenicity in Practice 38
References 38
Chapter 4. Anaemia and haematinics in pregnancy 41
Haematological Changes in Pregnancy 41
Iron 42
Folic Acid 49
Interpretation of Investigations during Pregnancy 51
Megaloblastic Anaemia and Pregnancy 52
Vitamin B12 53
Haemoglobinopathies 54
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency 56
Rare Haematological Diseases in Pregnancy 56
Drugs Administered to or Taken by the Mother during Pregnancy which may Cause Haematological Abnormality in the Neonate 57
Drugs Given to the Mother to Treat a Haematological Condition which may adversely Affect the Fetus 58
References 59
Chapter 5. Analgesia in pregnancy 62
Aspirin and Related Drugs 62
Aspirin as an Inhibitor of Prostaglandin Biosynthesis 63
Aspirin Pharmacokinetics and Placental Transfer 64
Effects on Fetal Circulation and Postnatal Adaption 65
Paracetamol 66
Conclusions 67
References 67
Chapter 6. Antibiotics and antimicrobial chemotherapy in pregnancy 70
Introduction 70
Teratogenicity and Toxicity of Antimicrobial Drugs in Pregnancy 70
Pharmacology and Pharmacokinetics 72
The Classification of Antibiotics 73
Antibiotics in Obstetric Practice 74
Treatment of Specified Conditions 75
References 80
Chapter 7. Drug treatment of heart disease in pregnancy 85
Digoxin 85
Diuretic Therapy 86
The Treatment of Arrhythmias 86
Hypertrophic Obstructive Cardiomyopathy ( HOCM ) 87
Antibiotic Prophylaxis in Patients with Heart Disease in Pregnancy 87
Cardiovascular Side-effects of Sympathomimetic Drugs 88
References 89
Chapter 8. Anticoagulants in pregnancy 92
Importance of Venous Embolism in Pregnancy 92
Venous Thrombo-embolism Treatment 92
The Prophylaxis of Thrombo-embolism 96
Artificial Heart Valves and Mitral Valve Disease 97
References 98
Chapter 9. Antihypertensive treatment in pregnancy 101
Introduction 101
Pathogenesis and Natural History of Hypertension in Pregnancy 101
Aims of Treatment 105
What Level of Blood Pressure to Treat? 105
Which Patients to Treat? 106
How to Treat? 106
Recommendations for Treatment of Hypertension in Pregnancy 118
References 120
Chapter 10. Drug treatment of gastrointestinal disorders in pregnancy 127
Introduction 127
Antacids, Mucosal Protective Agents and Antireflux Therapy 127
Therapy for Peptic Ulcer in Pregnancy 128
Antiemetic Therapy in Pregnancy 131
Laxative Therapy in Pregnancy 133
Antidiarrhoeals, Antimicrobials, Anthelmintics 135
Salazopyrine, Corticosteroids, Immunosuppressive Agents in Bowel and Liver Disease 137
Immunization Procedures and Maternofetal Transmission of Hepatitis B Virus (HBV) 140
Penicillamine in Liver Disease 140
Hepatotoxic Drugs in Pregnancy 140
Bile Acid Therapy for Gallstones in Pregnancy 142
Pancreatitis in Pregnancy 142
References 142
Chapter 11. Therapy for asthma in pregnancy 151
Natural History of Asthma in Pregnancy 151
The Treatment of Asthma 152
Acute severe asthma (Status Asthmaticus) 154
References 155
Chapter 12. Cytotoxic drugs in pregnancy 157
Tissue Effects 157
Effects on Female Fertility 158
Effects on Male Fertility 159
Effects of Cytotoxic Drugs on Subsequent Pregnancies 159
Carcinogenicity 161
Correlation between Clinical Experience and Animal Studies 161
Summary of Individual Drugs 163
Alkylating Agents 163
Antimetabolites 164
Low Birthweight 166
References 166
Chapter 13. Treatment of diabetes in pregnancy 169
Introduction 169
Classification 169
Complications of Diabetic Pregnancy 169
Screening for Diabetes in Pregnancy 171
The Combined Diabetic-Antenatal Clinic 172
The Treatment of Chemical Diabetes in Pregnancy 172
Oral Hypoglycaemic Agents 173
Management of Insulin-dependent Diabetics in Pregnancy 174
The Management of Labour in the Pregnant Diabetic 175
The Management of Premature Labour 175
Diabetic Pregnancy Associated with Complications 176
Congenital Abnormalities in Diabetic Pregnancy 176
References 177
Chapter 14. Treatment of threatened and recurrent abortion 179
The Natural History of Threatened and Recurrent Abortion 179
The Diethylstilboestrol Problem 181
Treatment of Threatened and Recurrent Abortion 182
Recurrent Abortion 182
Threatened Abortion 183
The Question of Hormone Imbalance 183
Recommendations for Treatment 189
References 189
Chapter 15. Tocolytic therapy for preterm labour 195
Introduction 195
Definition 195
Frequency and Consequences of Preterm Labour 195
Aetiology of Preterm Labour 196
Mechanism of Uterine Activity 197
Selection of Patients for Treatment 198
Tocolytic Substances—Beta-mimetics 199
Miscellaneous Substances with Tocolytic Action 217
Conclusions 219
References 220
Chapter 16. Prophylactic treatment of idiopathic respiratory distress syndrome 232
Introduction 232
Pulmonary Surfactant and the Pathogenesis of IRDS 233
Drugs—Animal Studies 235
Drugs —Human Studies 238
References 241
Chapter 17. Drug treatment of thyroid and adrenal disease during pregnancy 245
Thyroid Disease 245
Adrenal Disease 255
References 258
Chapter 18. Bromocriptine, hyperprolactinaemia and pregnancy 264
Introduction 264
Human Prolactin 264
Investigation and Management of Hyperprolactinaemia 265
Bromocriptine Pharmacology 267
Clinical Use of Bromocriptine 268
Conduct of Bromocriptine-induced Pregnancy 270
Outcome of Bromocriptine-induced Pregnancies 271
Other Drugs for Hyperprolactinaemia 273
References 273
Chapter 19. Antiepileptic drugs, pregnancy and the newborn 277
Introduction 277
Effect of Pregnancy on Epilepsy 277
Kinetics of Antiepileptic Drugs During Pregnancy 278
Effect of Epilepsy and Antiepileptic Drugs on Pregnancy and Labour 284
Effect of Epilepsy and Antiepileptic Drugs on the Offspring 285
Antiepileptic Drug Disposition in the Newborn 291
Antiepileptic Drugs and Breastfeeding 292
Family Planning in the Epileptic Patient 294
Antiepileptic Drugs in Pregnancy and Puerperium: Summary and Recommendations 294
References 295
Chapter 20. Treatment of renal disease in pregnancy 301
Normal Renal Physiology of Pregnancy 301
Urinary Tract Infections in Pregnancy 303
Pregnancy-induced Hypertension 304
Pregnancy in the Hypertensive Woman 305
The Pregnant Patient with Glomerular or Tubulointerstitial Disease 306
Pregnancy in Lupus Nephritis 309
Pregnancy on Dialysis and after Transplantation 310
Chronic Renal Disease Appearing during Pregnancy 311
Renal Stones during Pregnancy 311
Acute Uraemia in Association with Pregnancy 312
References 312
Chapter 21. Prostaglandins in pregnancy 316
Introduction 316
Synthesis of Natural Prostaglandins 316
Physiological Role of Prostaglandins in Pregnancy 316
Prostaglandins for Therapeutic Abortion 319
Prostaglandins for Induction of Labour 323
References 329
Chapter 22. Oxytocic drugs in labour 337
Introduction 337
Oxytocin 337
Naturally Occurring Oxytocin 338
Actions of Oxytocin 338
Metabolism of Oxytocin 339
Administration of Oxytocin 339
Dosage 339
Quantitation of Effect 340
Indications and Contraindications 341
Side-Effects 344
References 346
Chapter 23. Analgesia in labour 350
Introduction 350
Narcotic Analgesics 350
Extradural Opiates 354
Patient Administration 354
Assessment of a New Method of Analgesia 355
Inhalation Analgesia 355
Extradural Analgesia 357
Local Anaesthetic Agents 357
Maternal Mortality due to Anaesthesia and Analgesia 359
General Anaesthesia 361
Drugs used in General Anaesthesia 363
Maintenance Anaesthesia 366
References 367
Chapter 24. Effects of perinatal drugs on the newborn baby 373
Sedatives and Analgesia in Labour 373
Measurement of the Behavioural Effects of Drugs on the Newborn 374
General Anaesthesia 375
Epidural Anaesthesia 375
The Comparative Advantages of Different Methods of Analgesia 376
References 377
Chapter 25. Drugs and breastfeeding 379
Introduction 379
Advantages of Breastfeeding 379
Medication in the Puerperium 379
Drugs to Control Lactation 380
Passage of Drugs into Breast Milk 381
Specific Drugs 385
References 388
INDEX 392