Insulintherapie in der Schwangerschaft

The paper focuses on the special requirements of insulin therapy in pregnant women with diabetes because glucose goals, frequency and timing of glucose monitoring, and the dynamics of insulin adjustment differ substantially from when a woman is not pregnant. Planning of pregnancy with preconceptional optimizing of glucose control is essential; there is good evidence that the level of HbA_1c seems to determine the whole course of pregnancy. Studies have shown that there is no significant difference in achievement of good perinatal outcome comparing insulin application by insulin pump or by intensified conventional insulin therapy (ICT); the same is valid for human insulin versus analogs. Meanwhile, long-term analogs are also considered safe in pregnancy. Glucose goals are substantially lower than outside pregnancy but individual maternal risk of hypoglycemia must be taken into account. Personal consultation with a diabetologist at least every 2 weeks is highly recommended to adjust the rapidly changing insulin demand during the course of pregnancy. Fetal growth as a parameter of potential over- or undernutrition must also be considered. Standards at the delivery hospital for glucose and insulin management of the fetus during and after delivery are required. The same principles of insulin therapy are valid for women with type 2 diabetes. Insulin demand can be very high in the third trimester, and sometimes glucose goals can be reached only by additional off-label use of metformin. In women taking oral agents before pregnancy it is recommended to switch to insulin before conception. During breast feeding, women should stay on insulin for better glucose control.     

Lebererkrankungen in der Schwangerschaft

In pregnancy physiologically induced altered levels in liver function tests have to be distinguished from liver diseases. These can be divided into clearly pregnancy-associated and liver diseases coincidentally occurring with pregnancy, such as gall-stones, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson??s disease, hepatitis B and C infections and cirrhosis of the liver. Pregnancy-associated liver diseases include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, preeclampsia/eclampsia, the hemolysis, elevated liver tests and low platelets (HELLP) syndrome and acute fatty liver of pregnancy. A close collaboration between obstetricians and hepatologists is recommended. In terms of pregnancy-related entities this often means prompt delivery of the neonate, whereas in pregnancy-independent liver diseases best supportive care including supervision of the embryo/fetus has priority.     

Pharmakotherapie in der Schwangerschaft

Most acute and chronic diseases do not require termination of a pregnancy nor is a pregnancy a reason to withhold necessary drug therapy. As many pregnancies are unplanned, any drug treatment during reproductive age should consider the occurrence of a pregnancy. Wherever possible, only medicinal drugs with sufficient documentation in pregnant women not indicating developmental toxicity should be chosen. There are acceptable drugs for the majority of diseases, although many of them are labeled as contraindicated during pregnancy. This article provides an overview on prenatal risks of ACE-inhibitors, AT II-receptor antagonists, antiepileptics, SSRI, atypical neuroleptics, lithium, coumarin anticoagulants, retinoids, selected antibiotics, immunomodulatary drugs and provides treatment recommendations for the most common diseases.     

Reflux in der Schwangerschaft

Gastroesophageal reflux occurs often in pregnancy and is usually interpreted as being intrinsically related to pregnancy and thus not a “real disease.” If the reflux symptoms are inadequately cared for, then gastroesophageal reflux disease (GERD) can have a severe affect on the quality of life of the pregnant woman. The main cause of reflux during pregnancy is a decrease in the lower esophageal sphincter tonus due to hormone level changes brought on by the pregnancy. Symptomatic GERD during pregnancy should be treated according to the step-up algorithm put forth by the European consensus meeting guidelines in 2003, starting with specific lifestyle changes. Antacids are the medication of first choice. Should the symptoms persist, then histamine-2 receptor antagonists can be given. Proton pump inhibitors are not recommended for pregnant women by the consensus meeting guidelines.     

Insulintherapie in der Schwangerschaft

Pregnancy in women with diabetes mellitus represents a high risk for both mother and child. Before the introduction of insulin, pregnancy in diabetic women was an extremely rare occurrence. With the availability of insulin, women with insulin-dependent diabetes could also risk becoming pregnant, although maternal mortality was still around 10% and fetal mortality 45–50%. During the 1960s perinatal mortality remained at approximately 20%. In recent decades, however, mortality and morbidity of both mother and child have been drastically reduced by improved therapeutic options and close interdisciplinary care by specialized teams. However, in comparison to non-diabetic pregnant women there is still a 3–5 times higher risk of congenital malformation, and perinatal mortality is also still higher than in children of healthy mothers.     

Arzneimitteltherapie in der Schwangerschaft

Drug therapy during pregnancy may be beneficial in its ability to influence a disease, but may also be associated with adverse effects on developmental processes of the child. A thorough risk–benefit analysis is needed and must balance interests of mother and child. Evidence concerning drug use during pregnancy is often sparse and further clinical studies are desirable to better clarify the beneficial or harmful potential of drugs. At some time during pregnancy, the majority of women take pharmaceuticals and, thus, are exposed to potential teratogens. Therefore, it is important to understand the variability of potentially adverse influences, and it remains a priority to avoid accidental exposure to teratogens especially in the first trimester. If drugs are used off-label, careful justification, documentation, and informed consent of the pregnant women are obligatory. This article also summarizes selected pharmacotherapeutical strategies for common gastroenterological symptoms and diseases in pregnancy.     

Therapie der pulmonalarteriellen Hypertonie

Current international guidelines on the treatment of pulmonary arterial hypertension (PAH) are compiled by the European Society of Cardiology and the American College of Chest Physicians. The classification of pulmonary hypertension and guidelines on diagnosis and therapy were last adopted at the 4th World Congress of PAH in Dana Point (California) in the year 2008. Based on these guidelines this article presents an overview of the current therapy recommendations for patients with PAH corresponding to group 1 of the diagnostic WHO classification of pulmonary hypertension. Here it is recommended that diagnostic and therapy should be carried out in an expert centre. The therapy forms for PAH can be classified into basic therapy (e. g. oral anticoagulants, diuretics and oxygen therapy) and specific therapy (e. g. phosphodiesterase-5 inhibitors, endothelin receptor antagonists and prostanoids). Finally, some new substances will be presented which have already progressed relatively far in the clinical development.     

Therapie der pulmonalen Hypertonie

Prostanoids and endothelin receptor antagonists (ERA) currently possess the largest practical value for therapy of pulmonary hypertension. In future, phosphodiesterase inhibitors will likely gain importance. Among the ERA, bosentan was approved by the European Medical Agencies (EMEA) and in America (FDA). Bosentan is currently the only approved oral medication and normally represents the therapy of first choice in pulmonary arterial hypertension (PAH). The first approved prostanoid, epoprostenol, is currently the first choice only for decompensated right heart failure in PAH. Alternatively, subcutaneous treprostinil can be applied. It has a longer half-life and is less risky and expensive compared to epoprostenol but did not receive EMEA approval. Beraprost, an oral prostanoid, was not approved by either the EMEA or FDA. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity and was approved by the EMEA and in Australia. Alternatively, iloprost is being used as a continuous intravenous infusion, which has been approved in New Zealand. The phosphodiesterase-5 inhibitor sildenafil was significantly effective in small randomized controlled trials (RCTs). The results of a large RCT will soon be available.     

Behandlung der arteriellen Hypertonie

Arterial hypertension is the most common internal disease. Treatment is highly effective in lowering cardiovascular morbidity and mortality and is indicated based on total cardiovascular risk as assessed by all relevant risk factors. Target blood pressure is <140/90 mmHg, or with concomitant diabetes mellitus or renal insufficiency <130/80 mmHg. Lifestyle modifications are helpful, either alone or as an adjuvant to drug treatment, depending on the severity of the disease. First-line drugs are diuretics, calcium antagonists, ACE inhibitors, AT1 blockers and β blockers. In most cases, combination therapy is appropriate. Possible treatment strategies include stepped care, initial low-dose combination therapy and sequential monotherapy.     

Diagnostik der pulmonalen Hypertonie

Commonly, pulmonary hypertension is clinically suspected because of unexplained exertional dyspnoea or as a chance finding in clinical examination revealing signs of right heart failure. The systematic diagnostic approach and exact classification is based on the Venice classification. Basic investigations include ECG, chest radiograph, lung function studies and echocardiography. Echocardiography is the most important investigation for the diagnosis of pulmonary hypertension. It also serves as non invasive control during treatment and as the main screening test for pulmonary hypertension. Echocardiographic criteria of pulmonary hypertension are a dilated and hypertrophied right ventricle, paradoxic septum movement, a dilated right atrium, and a distended inferior Vena cava. Using Doppler echocardiography, the right ventricular and thus pulmonary arterial systolic pressure can be determined from the tricuspid regurgitant jet velocity. CT of the chest serves to exclude pulmonary embolism and interstitial lung disorders. Cardiac MRI is increasingly being used for analysis of right ventricular morphology, function and haemdynamics. The 6 minute walk test and cardiopulmonary exercise test are used to assess severity and response to treatment and give prognostic information. For the definite diagnosis of pulmonary hypertension, right heart catheterisation is required for the determination of the pulmonary vascular resistance and pharmacological testing of “reversibility”.     

Diagnostik der pulmonalen Hypertonie

A meticulous history, physical examination, and basic exams including ECG, chest X-ray and pulmonary function tests as well as the targeted search for risk factors lead to the diagnosis of pulmonary hypertension. An elevated pulmonary arterial pressure is primarily detected by Doppler echocardiography. It is important to assess the clinical severity according to the WHO (modified NYHA) functional class and by exercise testing (6-min walking test, cardiopulmonary exercise test). An interdisciplinary approach is needed to identify treatable underlying conditions such as pulmonary, cardiac, liver, collagen vascular, and chronic thromboembolic disease. This includes modern imaging techniques such as CT and MRI. In cases of significant pulmonary arterial hypertension, right heart catheterisation including pharmacological reversibility testing is indispensable. Once the diagnosis has been established it is advisable to contact a centre specialising in pulmonary hypertension.     

Leitliniengerechte Differenzialtherapie der Hypertonie

The goal of antihypertensive therapy is to lower blood pressure and, by doing so, to decrease cardiovascular risk. Life style changes and drugs are available for the treatment of hypertensive patients. In order to reach the target blood pressure, most patients with hypertension need drug treatment in addition to life style changes. In all hypertensive patients, the target blood pressure is <140/90 mmHg. In patients with diabetes mellitus, with chronic renal failure as well as in patients with complications of hypertension and, thereby a very high cardiovascular risk, the target blood pressure is <130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors and angiotensin receptor blockers are the drugs of first choice in the treatment of hypertension. The selection among these drug classes has to consider probable side effects as well as accompanying diseases and complications of hypertension. One should also take into account that most of the beneficial effects of antihypertensive therapy is due to the decrease of blood pressure per se and that the majority of hypertensive patients require the combination of two or more antihypertensive drugs in order to reach the target blood pressure.     

Diagnostik der pulmonalen Hypertonie

Chronic pulmonary hypertension (PH) is defined as a permanently increased mean pulmonary artery pressure ≥25 mmHg as assessed by right heart catheterisation and is associated with a poor prognosis without therapy. Depending on pathological, pathophysiological and therapeutic characteristics, clinical conditions with PH are classified into five groups. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PH. The first symptoms of PH are non-specific; therefore an early diagnosis is difficult. The current guidelines propose a new diagnostic algorithm to improve the precise diagnostic workup. In any case of suspected PH transthoracic echocardiography should be performed. If signs of PH are found, underlying left heart disease and lung diseases need to be searched for. In the case of exclusion or presence of “out of proportion PH”, which is not explained by underlying disease, a systematic evaluation is needed to clarify the specific aetiology and clinical group of PH and to quantify the functional and haemodynamic impairment.     

Zerebrale Folgen der Hypertonie

Hypertension is the most important risk factor for stroke and vascular dementia. Antihypertensive treatment reduces stroke risk by 40%. Most probably, all antihypertensive drugs are equally effective with the exception of alpha blockers. One study showed superiority of an angiotensin (AT) II antagonist versus beta blocker in patients with hypertension and left ventricular hypertrophy. Blood pressure is increased in many patients with acute stroke. In this phase, sudden drops in blood pressure should be avoided. All guidelines concerning antihypertensive treatment in acute stroke are not based on evidence. For secondary prevention, the combination of an angiotensin- converting enzyme (ACE) inhibitor and diuretic reduced strokes by 28% after transient ischemic attack (TIA) or a first stroke. Whether this is a drug-specific effect or due to lowering blood pressure per se is investigated at the moment. Antihypertensive treatment can reduce the incidence of vascular dementia and cognitive impairment.