1. Introduction The risk of stroke and heart failure in patients with gestational hypertension is significantly higher during pregnancy due to hemodynamic changes, and it has become the main cause of maternal mortality in China. In the clinical work of obstetrics, antihypertensive drugs are mainly used in the treatment of combined hypertension in pregnancy and gestational hypertension syndrome. 2.Indications for the application of antihypertensive drugs in patients with hypertension The treatment principles for moderate and severe hypertension are: antispasmodic, antihypertensive, sedation, reasonable blood volume expansion and diuresis, and timely termination of pregnancy. The occurrence of complications of hyperemesis is more or less related to the increase of blood pressure, so antihypertensive treatment is beneficial to reduce the occurrence of complications. In obstetric clinical practice, antihypertensive drugs are indicated for patients with high blood pressure, especially high diastolic blood pressure. Generally, those with diastolic blood pressure equal to or exceeding 14.6kpa (110mmHg) or mean arterial pressure equal to or exceeding 18.7kpa (140mmHg) should be actively treated with antihypertensive therapy. The drug of choice should not affect the cardiac output, renal blood flow and uteroplacental perfusion. The diastolic blood pressure should be lowered to 12.0-13.3kpa (90-100mmHg) and the mean arterial pressure to 14.1-16.0kpa (106-120mmHg) after medication. Excessive hypotension may aggravate the uteroplacental underperfusion and endanger the fetus. 3. Indications for the application of antihypertensive drugs in patients with combined hypertension in pregnancy The management of combined hypertension in pregnancy is different from that of hypertension, which generally requires blood pressure control with antihypertensive drugs, but it is controversial whether patients with combined mild hypertension in pregnancy need to apply antihypertensive drugs. It is generally believed that patients with mild hypertension in pregnancy do not need to apply antihypertensive drugs routinely, but if the diastolic blood pressure is persistently above 14.6kpa (110mmHg), appropriate antihypertensive treatment should be given. If proteinuria, edema and other symptoms of hypertension appear, more active treatment should be given. 4. Types of antihypertensive drugs and drug selection Antihypertensive drugs can be broadly divided into the following categories according to their mechanism of action and characteristics: (1) vasodilators; (2) alpha and beta blockers; (3) calcium channel blockers; (4) central antihypertensive drugs; (5) angiotensin converting enzyme inhibitors (ACEI); 6) other antihypertensive drugs. There is a wide variety of antihypertensive drugs, but most of them lack experience in application during pregnancy. In addition to the maternal effects of drugs, the safety of the fetus must be taken into account. Here is a brief introduction to the most commonly used antihypertensive drugs during pregnancy. 4.1 Vasodilators Vasodilators include: hydrazidiazine (hydrazinebendazole), diazepam, nitroglycerin, sodium nitroprusside, etc. 4.1.1 Hydrazidiazine is classified as Class C by the U.S. Food and Drug Administration (FDA). Hydrazidiazine has no sympathetic blocking effect and can directly relax the smooth muscle of small arteries, thus reducing the systemic vascular resistance. It is well absorbed orally and is mainly metabolized and converted by acetylation in the liver. It is administered orally for mild hypertension at 25-50 mg three times daily, and intravenously at 12.5-25 mg in 5% glucose solution 250-500 ml for intravenous infusion, usually at 20 drops/min-30 drops/min. Hydralazine readily passes through the placenta and the concentration of the drug in the umbilical cord blood is slightly higher than in the maternal blood. To date, there have been no reports of fetal malformations caused by the application of this product. Because hydrazidiazide does not affect utero-placental perfusion and is safer for the fetus, it is more commonly used for the treatment of hypertension in pregnancy. 4.1.2 Diazoxide FDA classification is Class C. Diazoxide is a non-diuretic thiazide derivative and an arterial dilator. Diazoxide has been used in patients with severe hypertension in combination with pregnancy. However, it should be used with caution because it can cause hypotension and inadequate utero-placental perfusion, and can cause fetal bradycardia. It has been reported in the literature that the use of this product during labor has an inhibitory effect on contractions and can increase blood glucose in newborns. 4.1.3 Nitroglycerin is classified as Class C by FDA. Nitroglycerin directly relaxes vascular smooth muscle, dilates peripheral blood vessels, reduces peripheral resistance, decreases cardiac output, reduces cardiac load, and decreases myocardial oxygen consumption. Since its introduction, nitroglycerin has been used for the prevention and treatment of angina pectoris for more than 100 years. Some people have tracked pregnant women with angina pectoris, and sublingual nitroglycerin has no adverse effect on the fetus. Some scholars have applied nitroglycerin to patients with hypertension and observed its effect on umbilical-placental vascular resistance. It has been found that intravenous nitroglycerin treatment for severe hyperemesis is effective in lowering blood pressure and significantly reducing umbilical-placental vascular resistance, which helps improve the intrauterine environment of the fetus, and no adverse effects of nitroglycerin on the fetus have been found. The dose is 5-10mg added to 250-500ml of 5% glucose solution and administered intravenously, starting from 4 drops/min, and the general effective dose is 16 drops/min 20 drops/min. 4.1.4 Sodium nitroprusside, classified as Class C by FDA, is a strong, fast-acting vasodilator with direct diastolic effects on both resistance and volume vessels, and can reduce cardiac preload and afterload. In addition to hypertensive crisis, it can also be used to treat acute left heart failure and acute pulmonary edema. Since the 1990s, many scholars at home and abroad have used sodium nitroprusside to treat severe hyperemesis with good results. Sodium nitroprusside can pass through the placenta and may lead to fetal cyanide poisoning, so only a few patients with severe hyperemesis are considered to use sodium nitroprusside when other antihypertensive drugs are ineffective due to high blood pressure during labor and delivery or after delivery. More experimental and clinical evidence shows that the toxicity of sodium nitroprusside is mainly concentration-related, and cyanide poisoning can be caused when the rate of drug entering the body exceeds the rate of thiocyanide formation. In addition, animal experiments have proved that after 24 hours of continuous intravenous administration of sodium nitroprusside to pregnant sheep, it can cause in utero poisoning death of sheep kids. The dose is 50mg with 5% glucose 500ml, start with 6 drops/min intravenous drip, after that blood pressure is measured every 5 minutes, adjust the drip rate according to the decrease of blood pressure, each time the increase of the number of drops does not exceed 2 drops/min. The maximum dose in 24 hours should not exceed 100mg. sodium nitroprusside solution must be protected from light, and can be covered with tinfoil. The prenatal application should not exceed 24 hours to avoid fetal toxicity. 4.2 Alpha and beta blockers mainly include labetalol, phentolamine, metoprolol, propranolol, etc. 4.2.1 Labetalol is classified as Class C by FDA. Labetalol has not only beta-blocking effect but also alpha-blocking effect. The blocking effect on α receptors is selective, only acting on α1 receptors but not on α2 receptors. The blocking effect on β receptors is non-selective, acting on both β1 and β2 receptors. Its application lowers blood pressure and slows heart rate, but does not inhibit the myocardium or reduce cardiac blood output. Labetalol crosses the placenta, and the mean drug concentration in umbilical blood is about 40-80% of the maternal blood concentration. There are no reports of fetal malformations caused by the application of this product. It is generally considered safe and effective for the treatment of severe hyperemesis gravidarum in the middle and late stages of pregnancy. Changes in fetal heart rate after intravenous drip or oral administration of this product are within the normal range, and no suppressive cardiovascular reactions have been observed in newborns. Moreover, some studies have demonstrated that this product does not reduce uteroplacental blood perfusion, which is beneficial to fetal growth and development. It has also been reported in the literature to promote fetal lung maturation. It has also been reported to promote uterine contractions and should not be used in patients with a tendency to preterm labor. The oral dose should be started at 100mg twice or three times a day. It can be increased to 200mg 3-4 times daily. In severe hypertension, 20mg of this product may be given intravenously and may be repeated after 10 minutes, up to 4 times. It can also be given intravenously at 0.2-0.6mg/min. It should not be used in the presence of heart failure. 4.2.2 Phentolamine FDA classification as Class C. Phentolamine is an alpha-blocker, which can relax blood vessels, lower blood pressure and pulmonary artery pressure, have an excitatory effect on the heart, and increase cardiac blood output. It is mainly used for the treatment of hypertension caused by pheochromocytoma. In obstetric practice, it is also indicated for the treatment of patients with hypertension who present with a rapid increase in blood pressure or combined with left heart failure. Phentolamine has been reported to be prone to postural hypotension when administered intravenously, so care should be taken. When administering phentolamine intravenously, the drug concentration and drip rate should be adjusted according to the patient’s response. The usual dose is 10mg of phentolamine in 500ml of 5% glucose solution. No teratogenic effect of phentolamine has been found in animal experiments. 4.2.3 Metoprolol is classified as Class C by FDA. Metoprolol is a β1 receptor blocker, which can selectively act on the heart to slow down the heart rate, reduce the cardiac blood output and lower the systolic blood pressure. It is also used in obstetric clinics to treat hypertension and tachycardia during pregnancy. Metoprolol readily crosses the placenta. In late pregnancy, the concentration of the drug in the umbilical cord blood is almost identical to that in the maternal blood. No teratogenic effects have been found in animal studies. Most data indicate that it is safe for the fetus when used to treat hypertension during pregnancy. The long-term use of this drug in pregnant women may result in a slight decrease in fetal weight, but it is difficult to exclude whether this is related to the effects of the mother’s primary disease. β-blockers may reduce the responsiveness of the fetal sympathetic nervous system and decrease the baseline fetal heart rate, so a false negative may occur in the no stimulation test (NST) during administration. Theoretically, beta-blockers have a pro-uterine contraction effect, so they should not be used in pregnant women with signs of preterm labor. Because of the long-lasting beta-blocking effect on newborns, newborns exposed to this product before birth should be closely monitored for bradycardia and other symptoms of beta-blockade during the first 1-2 days of life. The dose should be started at 100 mg daily, divided between morning and evening, and increased to 400 mg/d if necessary, divided between morning and evening. 4.2.4 Propranolol FDA classification as Class C. Propranolol is a non-selective beta-blocker. It has been used in clinical application for more than thirty years. It is widely used in obstetrical clinics and has been used in pregnant women with hyperthyroidism, pheochromocytoma, heart disease, hypertension, non-hypoxia-induced tachycardia and arrhythmia in fetuses. It is able to pass through the placenta and no teratogenic effects have been found in animal studies, but embryotoxic effects can occur at excessive doses. Propranolol has a pro-uterine contraction effect, so it should not be used in pregnant women with preterm labor triggers and signs of preterm labor. Prolonged use of propranolol or daily doses exceeding 160 mg may cause adverse effects on the fetus, such as intrauterine growth retardation and bradycardia. Respiratory depression and hypoglycemia may occur in the fetus at birth. The dose starts at 5mg once 4 times a day and can be increased to 100mg/d later. 4.3 Calcium channel blocking drugs Currently, nifedipine is more commonly used in obstetrics and is classified as Class C by the FDA. Nifedipine is a dihydropyridine calcium channel blocking drug, which can relax vascular smooth muscle, dilate coronary arteries and small peripheral arteries, and lower blood pressure. It is widely used in the treatment of pregnancy and postpartum hypertension, and its antihypertensive effect is relatively mild. It is generally believed that this product does not reduce the perfusion of the uterus1 and has no adverse effect on the fetus. The most common adverse effects are flushing, headache, and tachycardia. Animal studies have found teratogenic effects on fetuses in pregnant rats at a maximum dose of 30 times the human dose of nifedipine. In humans, no adequate and controlled studies have been reported on the teratogenic effects of nifedipine. Therefore, this product should be used with caution in early pregnancy. The use of calcium channel blockers in conjunction with magnesium sulfate may cause a dramatic drop in blood pressure, and care should be taken. The common dose of this product is 10mg per time, sublingual, every 4-6 small 1 time. 4.4 Central antihypertensive drugs Currently, methyldopa and colistin are more commonly used. 4.4.1 Methyldopa is classified as Class C by FDA. It is converted into α-methylnorepinephrine in the central nervous system, which agonizes α receptors in the vasomotor center, thereby inhibiting peripheral sympathetic nerves and lowering blood pressure. The hypotensive effect of methyldopa is relatively mild and can pass through the placenta, and the concentration of the drug in the umbilical cord blood is close to that of maternal blood. It has been widely used in the treatment of gestational hypertension and no serious adverse effects on the fetus have been found, nor has it been reported to be teratogenic to the fetus. 4.4.2 Colistin is classified as Class C by FDA. It is also a central antihypertensive drug with strong antihypertensive effect and is suitable for all kinds of hypertension. The hypotensive principle of this product is to agonize the central α2 receptor, which inhibits the vasomotor center, and to agonize the peripheral α2 receptor, which causes negative feedback, both of which lower blood pressure. It can pass through the placenta, and the drug concentration in maternal blood and umbilical cord blood is relatively similar. It has been used in all stages of pregnancy, but less frequently in early pregnancy. There are no reports of fetal malformations caused by colistin application. The oral dose is 0.075 C0.15mg three times a day, and the maximum daily dose is gradually increased to 0.8mg. 4.5 Angiotensin-converting enzyme inhibitors A representative drug is captopril, which is classified as Class D by FDA. aldosterone system. The oral dose is 12.5-25 mg per dose, 3 times daily. It is effective and safe for the treatment of hypertension in non-pregnant women. It has been found in animal studies to have an embryocidal effect and to increase fetal mortality. It was also observed in pregnant rabbits and sheep that captopril decreased utero-placental perfusion and caused intrauterine hypoxia in fetuses. The application of captopril in the middle and late stages of pregnancy may reduce uteroplacental blood perfusion and cause intrauterine growth retardation in the fetus. In addition, it may cause hypotension in the fetus and impair renal function, resulting in oliguria or anuria, and consequently low amniotic fluid. 4.6 Others, such as cardiac natriuretic, have strong sodium excretion, diuretic and vasodilatory effects. Because it can inhibit the renin-angiotensin-aldosterone system, it can improve cardiac and renal function and treat hyperemesis. Artificial solid phase synthesized cardiac natriuretic factor III 100-300μg is added into 5% glucose solution 250ml intravenously for 30 minutes, once a day for 1-3 days. It has been reported in the literature that the application of cardiac natriuretic agent has good effect in treating patients with hyperemesis combined with heart failure, not only the heart failure is controlled, but also the blood pressure is restored to normal and the urine output is increased.