Diuretics: a contemporary pharmacological classification?

Abstract

Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. This traditional classification and the nomenclature of diuretics have not changed over the last decades, which means that it was not adapted to current pharmacological research. Modern approaches in the field of pharmacological nomenclature suggest the introduction of mechanism-based drug class designations, which is not yet reflected in the group of diuretics. Moreover, included drug classes have lost their relevance as diuretic agents. Carbonic anhydrase inhibitors, for example, are mainly used in the treatment of glaucoma. Newer agents such as vasopressin-2 receptor antagonists or SGLT2 inhibitors possess diuretic properties but are not included in the pharmacological group. This review discusses the currentness of the pharmacological classification of diuretics. We elaborate changes in the field of nomenclature, the contemporary medical use of classical diuretics, and new diuretic agents.

Keywords: Acetazolamide; Carbonic anhydrase inhibitors; Diuretics; Nomenclature; Pharmacological classification.

Fig. 1

Citation frequency of the medical indications of hypertension, heart failure, and glaucoma in the context of carbonic anhydrase inhibitors. PubMed searches were limited to titles and abstracts of articles. The additional filter “Journal Article” was applied, and the journal category was set to “MEDLINE.” The ratio per year is shown in percent. The ratio is defined as number of articles mentioning A: all CAIs and B: acetazolamide together with the medical indications of hypertension, heart failure, or glaucoma relative to the total number of articles citing CAIs and acetazolamide, respectively

Fig. 2

Clinical trials with acetazolamide drug intervention. Relative share by conditions. The search on clinicaltrials.gov was performed on October 14, 2021. In total, 118 clinical trials with acetazolamide drug intervention were found for various conditions. The proportion relative to the total number of clinical trials with acetazolamide drug intervention is shown in percent. ¹Edema: cerebral/macular/pulmonal edema, nephrotic syndrome. ²Other neurologic indications: acute cerebrovascular accident, aneurysma, cerebral vasospasm, cerebrospinal fluid leak, cognitive investigation, Landau-Kleffner syndrome, multiple sclerosis, neurocysticercosis, normal pressure hydrocephalus, schizophrenia, status epilepticus, subarachnoid hemorrhage. ³Other renal indications: Bartter syndrome, cisplatin nephrotoxicity, contrast-induced nephropathy, kidney calculi, obesity-induced hyperfiltration. ⁴Other pulmonary indications: alkalosis, hypercapnia, hypoxia, respiratory insufficiency, ventilator weaning. ⁵Other cardiovascular indications: Andersen-Tawil syndrome, chronic orthostatic intolerance, orthostatic hypotension, tachycardia, thoracic aneurysm. ⁶Others: cocaine use, H. pylori infection, PMM2-CDG (Jaeken syndrome), sickle cell disease, Thalassemia, validation of method to obtain the arterial input function