Higher doses of sotalol increase the risk for all of these possible side effects.In rare cases, the QT prolongation caused by sotalol can lead to the development of life-threatening torsade de pointes (TdP) polymorphic ventricular tachycardia. Across several clinical trials, 0.6% of oral sotalol patients with supraventricular abnormal heart rhythms (such as atrial fibrillation) developed TdP. For patients who had a history of sustained ventricular tachycardia (abnormal rhythm lasting more than 30 seconds), 4% developed TdP. Risk increases with dosage, female sex, or having a history of an enlarged heart or congestive heart failure. The incidence of TdP for sustained ventricular tachycardia patients was 0% with an 80 mg daily dose, 0.5% at 160 mg, 1.6% at 320 mg, 4.4% at 480 mg, 3.7% at 640 mg, and 5.8% at doses greater than 640 mg. Due to this risk, the U.S. Food and Drug Administration requires affected individuals to be hospitalized for at least three days in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring upon starting or restarting sotalol. Mechanisms of action
Beta-blocker action
Sotalol non-selectively binds to both β1- and β2-adrenergic receptors preventing activation of the receptors by their stimulatory ligand (catecholamines). Without the binding of this ligand to the receptor, the G-protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels. A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium.
Untreated, preeclampsia can progress and turn into eclampsia which is much more severe with the addition of seizures. Eclampsia seizures could lead to uncontrollable twitching and a loss of consciousness, which could potentially lead to the death of the mother and or the baby. Cause
Intrauterine hypoxia can be attributed to maternal, placental, or fetal conditions. Kingdom and Kaufmann classifies three categories for the origin of fetal hypoxia: 1) pre-placental (both mother and fetus are hypoxic), 2) utero-placental (mother is normal but placenta and fetus is hypoxic), 3) post-placental (only fetus is hypoxic).Pre-placental hypoxia is most commonly caused by external hypoxic environments (such as high altitude). It can also be caused by maternal respiratory conditions (such as asthma), cardiovascular conditions (such as heart failure, pulmonary hypertension, and cyanotic heart disease), and hematological conditions (such as anemia). Conditions such as obesity, nutritional deficiencies, infections, chronic inflammations, and stress can also affect the maternal oxygen supply and fetal uptake.The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia.