Prescribing in Pregnancy, Breastfeeding and Paediatrics eBook Flashcards
Preconception advice
Avoid drugs (where possible), alcohol (although this is a controversial area!), smoking (definitely), vitamin A products
Decrease caffeine intake
Consider taking folic acid 400mcg per day as prophylaxis against neural tube defects(if the woman has epilepsy or has had a child previously with NTD then this should be 5 mg per day and should be prescribed by her GP)
Check whether the patient has been immunised against rubella (German measles). Rubella is not dangerous to the mother but is very dangerous to the unborn foetus
If the patient has a chronic illness such as epilepsy, she should consult with her GP prior to becoming pregnant as dosages of regular medications may need to be adjusted. In many cases, inadequate treatment of the underlying medical condition is more dangerous to the foetus than the drugs used to treat the condition
The trimesters of pregnancy
In medical terms, a woman’s pregnancy is described in weeks with the average pregnancy being 38-40 weeks in length. Each pregnancy passes through the three trimesters:
1st Trimester: 0 – 12 weeks
2nd Trimester: 12 – 28 weeks
3rd Trimester: 28 – 40 weeks
Stages of foetal development
Pre-embryonic (days 1 – 17): this is the time taken from fertilisation through cell division to arrive at the embryonic stage
Embryonic (days 18 – 56): organogenesis (the development of the primary organs) occurs during this time period
Foetal (from day 56 – i.e. week 8 – onwards): maturation, development and growth
Physiological changes during pregnancy
Vascular resistance changes from conception onwards. Initially there is a decline in maternal blood pressure until mid-way through the 2nd trimester (about 24 weeks) when
blood pressure begins to rise again towards pre pregnancy levels by the end of the pregnancy. The decrease in vascular resistance is compensated for by a gradual increase in heart rate and stroke volume during pregnancy and labour.
Maternal plasma volume increases by approximately 40% during pregnancy, part of which is due to an increase in red cell volume of about 15%. This increase in plasma volume decreases blood viscosity. There are also changes in the coagulation cascade with an increase in coagulation factors and a decrease in fibrinolysis. These changes are to minimise blood loss during labour, but also increase the risk of VTE during pregnancy.
Because of the increased plasma volume, renal blood flow is increased as is the glomerular filtration rate. This means that drugs which are renally excreted may be cleared much more quickly, particularly after the end of the first trimester, and upward dose adjustments may need to be made.
Serum albumin levels can decrease by up to 80% of normal by the end of pregnancy which means that drugs which are extensively plasma protein bound may be affected. Blood levels of such drugs should be adjusted for these lower albumin levels.
Increased progesterone levels during pregnancy relax smooth muscles, including those of
the oesophageal sphincter and the gut. Upward pressure from the uterus, combined with the relaxation of the oesophageal sphincter result in oesophageal reflux. Decreased gastrointestinal motility means that pregnant women are more prone to constipation and bloating
Teratogenicity
Harm to the foetus during pregnancy is very unlikely – less than 1% of birth defects can be attributed to prescription drugs. Most foetal damage occurs during the first trimester of pregnancy whilst organogenesis is in process. Teratogenicity is the term used to describe
the effects of drugs causing birth defects and is derived from the Greek “teratos” meaning monster.
The most common teratogenic effects are spina bifida (a neural tube defect), cleft lip and/or palate, renal failure, growth retardation
Spina bifida
Spina bifida means “cleft spine” and is an incomplete closure of the spinal column. The most severe form of spina bifida is myelomeningocele where a portion of the spinal cord itself protrudes through the back. In some cases the sacs are covered with skin; in others, tissue and nerves are exposed.
The most common teratogenic drugs
Anti-epileptics o Phenytoin o Valproate o Carbamazepine Lithium Warfarin Retinoids such as isotretinoin Danazol
Drugs which affect later pregnancy
ACE inhibitors. These may cause renal failure in the foetus
Antithyroid drugs (carbimazole, propylthiouracil). These may cause hypothyroidism in the foetus
Benzodiazepines. When these are taken in the third trimester, these can cause severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, reluctance to suck, apnoeic spells, cyanosis, seizures and impaired metabolic responses to cold stress. Benzodiazepine withdrawal syndrome can persist from hours to months after birth and requires careful management.
B-blockers (atenolol, but inferred for others). These may cause growth retardation. They may also cause neonatal hypoglycaemia and bradycardia. However, labetalol is
frequently prescribed for hypertension of pregnancy, but usually only in the 3rd trimester.
NSAIDs. These can cause closure of the ductus arteriosus in later pregnancy. The ductus arteriosus is the foetal blood vessel which joins the aorta and pulmonary artery in utero allowing the respiratory circulation to be bypassed as this is redundant as the source of blood oxygenation in the womb. In normal circumstances the ductus arteriosus closes soon after birth.
Warfarin. This affects both early and later pregnancy and can cause bleeding into the foetal brain.
How do we decide what to prescribe and what to avoid? examples
Paracetamol should be the only non-prescription analgesic recommended during pregnancy.
The safer antibiotics are the penicillins and cephalosporins. Urinary tract infections are common during pregnancy but the first line antibiotic, trimethoprim, is a folate antagonist and so should be avoided in the first trimester; cefalexin is therefore the preferred agent.
Heartburn is a common problem in pregnancy and very few pregnant women make it through without resort to an antacid of some sort! Care should be taken to recommend
those that have a low sodium content to prevent hypertension.
During pregnancy it is imperative that asthma is controlled as during an asthma attack the reduced oxygen that the mother receives also affects the foetus
Complications in pregnancy - Hyperemesis
More commonly known as ‘morning sickness’, hyperemesis affects approximately 70% of pregnant women during their first trimester. Hyperemesis tends to resolve by 20 weeks, but it can continue for longer in some women. Approximately 1% of women will develop
hyperemesis gravidarum, the cause of which is not fully understood. This severe nausea and vomiting can result in dehydration, weight loss and patients are often hospitalised as a result.
Morning sickness should be managed, wherever possible, by non-pharmacological methods including: Eating smaller meals, more frequently Avoiding spicy foods Avoiding caffeine Preventing fatigue Provision of emotional support
The first three points on this list also help in the non-pharmacological management of oesophageal reflux.
In severe cases of hyperemesis, pharmacological management may be required. Antihistamines, such as cyclizine and promethazine, are the preferred first line options with metoclopramide, ondansetron and prochlorperazine reserved for second line treatment.
Intravenous fluids may also be required as well as nutritional supplementation.
Complications in pregnancy - acid reflux
Up to 80% of women may be affected by acid reflux during pregnancy. First line management includes the avoidance of trigger factors such as spicy or fatty foods, tight clothing, big meals and smoking. If this is not sufficient or successful, then an antacid with or without an alginate may be recommended. Second line pharmacological therapy includes omeprazole or ranitidine, neither of which has been shown to be harmful to the foetus.
Complications in pregnancy - Hypertension and pre-eclampsia
Pregnancy-induced hypertension (PIH) is defined as a BP of greater than 140/90 mmHg beyond 20 weeks of pregnancy, resolving upon delivery. PIH affects about 10% of pregnancies.
Pre-eclampsia is defined as hypertension accompanied by pregnancy-induced proteinuria.
All pregnant women should have their BP checked and urine dipped for protein at each antenatal appointment to allow early detection of PIH and pre-eclampsia. Labetalol is the pharmacological treatment of choice for PIH; nifedipine or methyldopa may be used if labetalol is not tolerated or suitable.
Complications in pregnancy - Gestational diabetes
This condition is on the increase in the UK, most likely due to the increasing number of pregnant women who are obese. A urine dipstick test at each antenatal appointment will allow for early detection of the condition, which should resolve after delivery. If untreated, the risks of PIH, pre-eclampsia, premature birth and neonatal hyperglycaemia at birth are all increased.
Diet and lifestyle modifications are the first line treatment, with the aim of reducing the fasting blood glucose level to less than 5.3 mmoL/L. If this is unsuccessful, drug treatment should be started as soon as possible to prevent the complications listed above with oral metformin being used first-line. Insulin therapy may be used if treatment with metformin is unsuitable or unsuccessful.
Complications in pregnancy - Venous thromboembolism
As stated earlier in this eBook, the risk of VTE in pregnancy is increased due to the changes in the coagulation cascade which occur to minimise the loss of blood during labour. All women should receive a VTE assessment in early pregnancy to establish any risk factors and to initiate any treatment measures if necessary. Women at an increased risk of VTE should
be prescribed a low molecular weight heparin (LMWH) as prophylaxis, often for the duration of their pregnancy.
Drugs in breastfeeding
It is widely acknowledged that breastfeeding is highly beneficial for newborn babies and so it is best that drug therapy fits around this.
All drugs distribute into the breast milk to a greater or lesser extent except very large molecules such as insulin and warfarin. The extent of transfer to breast milk depends upon:
pKa. Basic drugs are more likely to cross into breast milk
Protein binding. Highly protein bound drugs are less likely to cross into breast milk
Lipophilicity. Highly lipophilic drugs are much more likely to cross into breast milk.
Therefore drugs that are acidic, highly protein bound and with a low lipophilicity are least likely to cross into the breast milk – e.g. NSAIDs.
Those drugs that are likely to exhibit a high concentration in breast milk are those that are basic, with low plasma binding and high lipophilicity – e.g. sotalol.
Younger babies may be at greater risk from drugs in breast milk as they are fed smaller amounts more often than older babies. However, the dilutional effect of the breast milk itself and the amount actually swallowed do reduce potential ill effects.
Maternal drug therapy is rarely a reason to avoid breast feeding. It is best to feed the baby immediately before a dose of a drug is taken. If non-compatible drugs are unavoidable, then the mother should express and discard any milk and wait for the elimination time for the drug (i.e. 4 x the half life) before feeding.