Drugs in pregnancy. Cardiovascular disease.

This chapter reviews the therapeutic armamentarium available for the treatment of cardiovascular disease during pregnancy. The management does not differ markedly from that of the non-pregnant population. Few drugs are absolutely contraindicated, although, for many, safety data are limited and caution is recommended. The potential risks to the fetus must be weighed against maternal benefit and the well-being of the pregnancy. Women of childbearing age requiring long-term medication should be offered pre-pregnancy counselling, and other non-pharmacological avenues, such as radio-frequency ablation for supraventricular arrhythmias, should be explored.     

Drugs in pregnancy. Respiratory disease.

Respiratory illnesses are the commonest cause of patient visits to physicians. Although the common cold, sinusitis and bronchitis may be lacking in drama, they account for a substantial amount of morbidity among women of reproductive age and are frequently encountered by physicians caring for pregnant women. Present knowledge about the management of these common conditions and the safety of the medications often used to treat them are reviewed in this chapter. Asthma and community-acquired pneumonia are more serious respiratory illnesses that are also often encountered in pregnancy. Present evidence suggests that community-acquired pneumonia is best treated empirically, with additional investigation usually necessary only if there is a failure of initial treatment. The recognition of asthma as an inflammatory condition has led to a very specific approach to its management that can readily and safely be applied to the pregnant woman. Treatment of HIV and tuberculosis should not be withheld during pregnancy because of the life-threatening nature of these infections and the importance of preventing vertical transmission.     

Gastrointestinal and liver disease in pregnancy

The gastrointestinal system and the liver undergo several physiological changes during pregnancy, an understanding of which is essential to distinguish pathology from normal pregnancy symptoms. This review includes the physiological changes that occur in the gastrointestinal system and liver in pregnancy, common conditions of the liver and gastrointestinal system which can present in pregnancy, including the appropriate investigations, management options and indications for specialist multidisciplinary input.     

Drugs in pregnancy. Drugs to avoid.

Drugs given in pregnancy can adversely affect the fetus in many ways. Anxiety about birth defects is a major parental concern during pregnancy. Doctors, midwives and their patients often seek information about the potential teratogenicity of drugs that are taken by, or prescribed for, the pregnant woman. Because no drug is entirely without side-effects, great caution should be taken when prescribing in pregnancy. The development of knowledge in understanding the use of drugs during pregnancy has been in stalemate in comparison to other areas of therapeutics, due mainly to difficulties in testing new products in pregnant women and lack of good quality research. In this chapter, we review current knowledge of the epidemiology of drug use among pregnant women, drug metabolism in pregnancy, adverse fetal and neonatal effects of drugs and specific effects of drugs that are relatively or absolutely contraindicated in pregnancy.     

Drugs in pregnancy. Anticonvulsants and drugs for neurological disease.

The use of anticonvulsant drugs in pregnancy presents unique challenges to clinicians and their patients. The need for control of maternal epilepsy must be balanced with the fetal and neonatal risks associated with anticonvulsant drugs. Anticonvulsant drugs may have potential effects on embryogenesis, neurological development, growth and subsequent paediatric progress. Drug selection and dose adjustment must be appropriate and based on a combination of known maternal and fetal risks as well as the clinical status of the patient. Overall, no one drug can be specifically recommended but monotherapy with most of the recognized first-line drugs will result in a satisfactory outcome. Polytherapy is associated with an increase in congenital malformations and should be avoided if possible. It is possible that newer second-line agents, for example, gabapentin, may be safer as add-on therapy. Neurological disorders such as migraine, and the less common conditions of myasthenia gravis and multiple sclerosis, may require the use of drugs which have not been well studied in pregnancy. Information is provided about the use of drugs to control symptoms and prevent disease progression in these disorders during pregnancy.     

Drugs in pregnancy. Pharmacokinetics in pregnancy.

Pharmacokinetics describes the handling of a drug by the body - how the drug is absorbed, distributed and eliminated and how these processes determine plasma concentrations of the drug. Changes in maternal physiology during pregnancy influence pharmacokinetics, and this may have important sequelae for drug dosing, especially for drugs for which adverse effects occur at concentrations within, or just above, the therapeutic range. For many drugs absorption is decreased and elimination increased, thus tending to reduce plasma concentrations. There are, however, relatively few specific data on pharmacokinetics in pregnancy, compared to the non-gravid state, because of the obvious ethical issues surrounding studies during pregnancy. Most therapeutic guidelines are thus based on observational studies and basic principles.     

Drugs in pregnancy. Endocrine disease (including diabetes).

This chapter reviews the treatment of endocrine disease in pregnancy, including diabetes mellitus, hypo- and hyperthyroidism, adrenal and pituitary disorders, and hyper- and hypoparathyroidism. Pregnancy in some of these disorders is relatively rare, so that management is often based on limited information and clinical judgement rather than on strong evidence-based criteria.     

Gastrointestinal disorders in pregnancy.

Gastrointestinal disorders constitute one of the most frequent complaints of pregnancy. An understanding of the mode of presentation and the incidence of the various gastrointestinal disorders will optimize care in obstetric patients. Disorders of the esophagus, stomach, duodenum, ilium, jejunum, colon, rectum, and appendix are individually discussed with reference to physiologic changes in pregnancy, infectious diseases, autoimmune disease, and ulcer formation.     

Drugs in pregnancy. Drugs for obstetric conditions.

For many reasons, including the fear of fetal anomaly, the recognition of pregnancy being a normal physiological process and maternal choice, few drugs are prescribed and used during pregnancy. Nevertheless, there are certain common obstetric conditions that are associated with significant maternal and perinatal morbidity and mortality where drugs play an important and necessary part in treatment. These conditions include termination of pregnancy, threatened preterm labour, induction of labour and post-partum haemorrhage. This chapter deals with the role of drug therapy in these obstetric scenarios. A large amount of obstetric clinical trial research has been dedicated to the management of these conditions.     

Drugs in pregnancy. Anticoagulants.

Pregnancy is a period of heightened coagulability and enhanced risk for thrombotic complications. Thromboembolism is the leading cause of maternal mortality. Anticoagulants are very useful during pregnancy for the acute treatment of venous thromboembolism and for the prevention of recurrent venous thromboembolism. They may also be beneficial in patients with thrombophilias, particularly among women who have experienced adverse pregnancy outcomes such as recurrent pregnancy loss. Anticoagulation is essential but problematic in the management of pregnant women with mechanical heart valve prostheses. When utilizing these medications among pregnant women the potential benefits must be balanced against the possibility of maternal haemorrhagic complications, adverse effects on the pregnancy or toxic effects on the fetus. This chapter summarizes current knowledge about the anticoagulant agents, their potential toxicities and their therapeutic role in pregnant women with various indications for anticoagulant therapy.     

Drugs in pregnancy. Antihypertensives.

Fifty per cent of pregnancies are unplanned, and 1-6% of young women have pre-existing hypertension. However, no commonly used antihypertensive agent is known to be teratogenic. ACE inhibitors (and angiotensin-receptor antagonists) should be discontinued due to fetotoxicity. Five to 10% of pregnant women have hypertension, of which pre-existing hypertension is but one type. There is consensus that severe maternal hypertension (blood pressure >or=170/110 mmHg) should be treated to minimize the risk of acute cerebrovascular complications. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus that mild-to-moderate hypertension in pregnancy should be treated. Clinical trials indicate that transient severe hypertension, antenatal hospitalization, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by normalizing blood pressure, but intrauterine fetal growth restriction may be increased. Methodological problems with published trials warrant cautious interpretation of these findings. Methyldopa and beta-blockers have been used most extensively, although atenolol may impair fetal growth in particular and should be avoided.     

Drugs in pregnancy. Rheumatological disorders.

Rheumatic diseases occur frequently in women of childbearing years, necessitating drug treatment during a concurrent pregnancy in order to control maternal disease activity and to ensure a successful pregnancy outcome. Inflammatory rheumatic diseases with mainly musculoskeletal involvement may cause acute episodes of arthritis. Autoimmune, systemic diseases may flare with manifestations of haematological, dermatological or renal disease or give rise to thromboembolism during pregnancy. Treatment with non-steroidal anti-inflammatory drugs, corticosteroids, anticoagulants, immunosuppressive or even cytotoxic drugs may be required to acquire disease control. Unfortunately, controlled studies on the use of antirheumatic drugs during gestation exist only for a few drugs. This chapter presents data on the use of antirheumatic drugs during pregnancy, addressing the risk of teratogenicity, possible long-term effects on the infant exposed to drugs antenatally, and maternal side-effects which interfere with pregnancy. Recommendations for pre-pregnancy counselling and necessary adjustment of drug treatment before and during pregnancy are given.     

Drugs in pregnancy

The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.     

Drugs in pregnancy. Prescribing for psychiatric disorders in pregnancy and lactation.

The most recent Confidential Enquiry into the causes of maternal deaths during the perinatal period in England and Wales (1994-1996) revealed that psychological illness was at least as important as hypertensive disorders. It is therefore important for obstetricians to be aware of a variety of psychiatric conditions as well as the psychotropic medication prescribed and sequelae of continuation or withdrawal of these drugs. Best management, of this particularly vulnerable group of women, requires close liaison with the psychiatric team. This chapter considers four groups of women most likely to be prescribed psychoactive drugs during the perinatal period: (i) women with mental illness wishing to conceive, (ii) women with mental illness who conceive while taking medication, (iii) those who become mentally ill while pregnant, and (iv) those who become unwell postnatally. Guidelines for treatment are discussed.     

Drugs to avoid in pregnancy

Drugs given in pregnancy can adversely affect the fetus in many ways. Anxiety about birth defects is a major parental concern during pregnancy. Doctors and their patients often seek information about the potential teratogenicity of drugs that are taken by or prescribed for the pregnant woman. Because no drug is entirely without side effects, great caution should be taken when prescribing in pregnancy. The development of knowledge in understanding the use of drugs during pregnancy has been in stalemate in comparison to other areas of therapeutics, mainly due to difficulties in testing new products in pregnant women and paucity of good quality research. In this article, we aim to review current knowledge of the epidemiology of drug use among pregnant women, drug metabolism in pregnancy, adverse fetal and neonatal effects of drugs and specific effects of drugs that are relatively or absolutely contraindicated in pregnancy.