Severe cases are seen by yellowing of the skin tone and yellowing of the conjunctiva in the eye.Gilbert syndrome has been reported to contribute to an accelerated onset of neonatal jaundice. The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency. This situation can be especially dangerous if not quickly treated, as the high bilirubin causes irreversible neurological disability in the form of kernicterus. Detoxification of certain drugs
The enzymes that are defective in GS – UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) – are also responsible for some of the livers ability to detoxify certain drugs. For example, Gilbert syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity. Cardiovascular effects
The mild increase in unconjugated bilirubin due to Gilbert syndrome is closely related to the reduction in the prevalence of chronic diseases, especially cardiovascular disease and type 2 diabetes, related risk factors, and all-cause mortality.
Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an abnormally fast heart rate. By working on the beta-1 receptor of the cardiac muscle cells, it yields both a chronotropic and inotropic effect. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines.Metoprolol is sold in formulations that can be taken by mouth or given intravenously. The medication is often taken twice a day. The extended-release formulation is taken once per day. Metoprolol may be combined with hydrochlorothiazide (a diuretic) in a single tablet.Common side effects include trouble sleeping, feeling tired, feeling faint, and abdominal discomfort. Large doses may cause serious toxicity. Risk in pregnancy has not been ruled out. It appears to be safe in breastfeeding. The metabolism of metoprolol can vary widely between patients, often as a result of hepatic impairment or CYP2D6 polymorphism. Care should be taken in patients with asthma; metoprolol should only be used in these patients when the benefits outweigh the risks, for example in heart failure. Stopping this drug should be done slowly to decrease the risk of further health problems.Metoprolol was first made in 1969, patented in 1970, and approved for medical use in 1982. It is on the World Health Organizations List of Essential Medicines. It is available as a generic drug.