This section summarizes all pertinent drugs and their potential use during pregnancy and breastfeeding.There are no uniform recom- mendations for the treatment of pregnant women yet. This also concerns the timing of treatment initiation and the selection of medications. Prescribing information for drugs on specific databases for pregnancy and lactation should be consulted. As drug treatment in pregnancy concerns the mother and the foetus, optimum treatment of both must be targeted. Whether drug treatment is necessary is dependent on the urgency of the indication.
In case of emergency, drugs that are not recommended by international agencies for use during pregnancy and breastfeeding should not be withheld from the mother. The potential risk of a drug and the possible benefit of the therapy must be weighed against each other.
VKA and LMWH have advantages and disadvantages during pregnancy, which are also discussed in the sections related to specific indications.However, comparison between studies is hampered by reporting differences, and conclusions concerning the safety of low-dose VKA (warfarin <5 mg daily) in the current literature are controversial.VKAs cross the placenta and their use in the first trimester can result in embryopathy (limb defects and nasal hypoplasia) in 0.6–10% of cases. Substitution of a VKA with UFH(unfractionated heparin) or LMWH in weeks 6–12 almost eliminates the risk of embryopathy. There is evidence that the embryopathy risk with VKA is also dose-dependent.The risk was 0.45–0.9% in pregnancies with low-dose warfarin according to two recent systematic reviews.In addition to the risk of embryopathy that is limited to the first trimester, there is a 0.7–2% risk of foetopathy (e.g. ocular and central nervous system abnormalities and intracranial haemorrhage) when VKAs are used in the second and third trimesters. Foetopathy has also been described with UFH but not with LMWH throughout pregnancy. Vaginal delivery while the mother is on VKAs is contraindicated because of the risk of foetal intracranial bleeding. Haemorrhagic complications in the mother occur with all regimens.
The efficacy and safety of several LMWH preparations was shown in a review of 2777 pregnant women treated for DVT or PE. The risk of recurrent VTE with therapeutic doses of LMWH was 1.15%. The observed rate of major bleeding was 1.98%. Heparin-induced thrombocytopenia is markedly lower with LMWH than with UFH, as is heparin-induced osteoporosis (0.04%).In clinically suspected DVT or PE, therapeutic LMWH should be given until the diagnosis is excluded by objective testing.
UFH does not cross the placenta either, but is associated with more thrombocytopenia (platelet levels should be measured every 2–3 days), osteoporosis, and more frequent dosing when given subcutaneously compared with LMWH.
Thrombolytics are considered to be relatively contraindicated during pregnancy and peripartum, and should only be used in high-risk patients with severe hypotension or shock.The risk of haemorrhage, mostly from the genital tract, is around 8%.There are more than 200 reported patients in whom streptokinase was mostly used and, more recently, recombinant tissue plasminogen activator (alteplase). Neither of these thrombolytics crosses the placenta in significant amounts. Foetal loss in 6% and preterm delivery in 6% of cases were reported.When thrombolysis is given, the loading dose of UFH should be omitted and an infusion started at a rate of 18 U/kg/h, and carefully adjusted according to the aPTT level. After stabilization of the patient, UFH can be switched to LMWH.
184.108.40.206 Renin–angiotensin–aldosterone system inhibitors:ACEI(angiotensin-converting enzyme inhibitors), ARBs(angiotensin receptor blocker
220.127.116.11 Beta-adrenergic blocking agents
Beta-adrenergic blocking agents are generally safe in pregnancy, but may be associated with increased rates of foetal growth restriction and also hypoglycaemia. Beta-1-selective drugs are preferred, except in TdP, as they are less likely to affect uterine contraction and peripheral vasodilation, and they have exhibited lower rates of foetal growth retardation. Examples are metoprolol and bisoprolol. Unselective beta-blockers such as atenolol have been associated with higher rates of foetal growth retardation .Among the alpha/beta-blockers, labetalol is a drug of choice for hypertension in pregnancy, and carvedilol used for HF therapy did not show any association with foetal growth retardation in a recently published small study with 13 patients receiving this drug.
CCBs do not seem to be associated with an increased incidence of congenital anomalies in humans.In one study with 721 pregnancies exposed to CCBs during the third trimester, an increased risk of neonatal seizures with CCBs was reported. Diltiazem is teratogenic in animals and only limited data in humans exist; thus, its use is only recommended in pregnancy if the potential benefit justifies the potential risk to the foetus. Verapamil is considered to be fairly safe during pregnancy, and is recommended as a second-line drug for rate control in AF and for the treatment of idiopathic sustained VTs in pregnant women.
Statins should not be prescribed in pregnancy or during breastfeeding to treat hyperlipidaemia since their harmlessness is not proven. However, in a review published in 2012, no evidence of teratogenicity of statins was found, but a harmful effect could not be ruled out due to small sample sizes.In a prospective case-control study of 249 foetuses exposed to statins, the rate of birth defects did not differ significantly between cases and controls.