Drug-induced Adverse Events
Diuretics
2021 Oct 13. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–.
ABSTRACT
Diuretics constitute a large family of medications that increase urine flow and induce urinary sodium loss and are widely used for therapy of hypertension, congestive heart failure, and edematous states. Diuretics in current use (and the year of their approval for use in the United States) include chlorothiazide (1958), hydrochlorothiazide (1959), bendroflumethiazide (1959), spironolactone (1960), chlorthalidone (1960), methyclothiazide (1961), polythiazide (1961), triamterene (1964), furosemide (1966), ethacrynic acid (1967), metolazone (1973), bumetanide (1983), indapamide (1983), amiloride (1986), acetazolamide (1986), torsemide (1993), and eplerenone (2002). Diuretics are typically classified as thiazide diuretics (bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone and polythiazide), loop diuretics (bumetanide, ethacrynic acid, furosemide, and torsemide), and potassium-sparing agents (amiloride, eplerenone, spironolactone, and triamterene). The carbonic anhydrase blockers acetazolamide (1986) and methazolamide (1959) are also diuretics, but are more commonly used for the therapy of glaucoma.
Diuretics are some of the most frequently used medications in medicine and are usually well tolerated. Common side effects are those that are caused by the diuresis and mineral loss such as weakness, dizziness, electrolyte imbalance, low sodium and potassium. Diuretics have not been associated with an appreciable increased rate of serum aminotransferase elevations and have rarely been associated with clinically apparent liver injury. Isolated case reports of idiosyncratic hepatotoxicity due to diuretics have been published, but there have been virtually no case series on individual diuretics or even whole class of drugs. The case reports that have been published provide only a very general pattern of injury that has not provided a clear clinical signature or suggestion that hepatotoxicity is a class effect among the thiazides and the loop diuretics. Switching from one diuretic to another has not been reported in any systematic fashion. Most information on hepatotoxicity is available on the commonly used diuretics which include (and the number of prescriptions filled in 2007 for each): hydrochlorothiazide (45 million), furosemide (37 million), triamterene (21 million), spironolactone (8 million), and metolazone, bumetanide, indapamide and torsemide (1 to 2 million each). Diuretics implicated in rare cases of drug induced liver injury include hydrochlorothiazide, acetazolamide, amiloride, spironolactone and triamterene.
The thiazide and loop diuretics are discussed as a class; the other diuretics as individual agents. Selected references are given together at the end of this introductory section.
Covid-19 Vaccines
2021 May 3. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–.
ABSTRACT
The Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is the cause of the pandemic of coronavirus disease (COVID-19) that was first detected in December 2019 in Wuhan, China and subsequently spread globally. By March 2020, COVID-19 was declared a global pandemic and within a year it accounted for more than 100 million cases and 2 million deaths. Also, within a year of its detection, vaccines against SARS-CoV-2 were developed using several methodologies including mRNA-, adenoviral vector- and recombinant DNA-technology. Several of these vaccines have been evaluated in large, placebo-controlled trials and found to be both safe and effective. Adverse events have been mild-to-moderate local reactions and transient systemic symptoms such as fatigue, nausea and headache. No hepatic specific adverse events have been described, although rare reports of thrombotic thrombocytopenia have occurred with the adenoviral based vaccines that sometimes involve portal or hepatic vein thromboses and some degree of liver dysfunction.