How do Thiazide Diuretics Work?
Understanding Bendroflumethiazide and Indapamide
Thiazide diuretics work to reduce the amount of sodium and water in the body and this makes them useful for treating hypertension or high blood pressure and edema two examples I’m going to give a thiazide diuretics the first is BendrofluMathiazide and the second is indapamide and the main indication for thiazide diureticsis hypertension but they can also be used to treat edema so to go through the mechanism of action of thiazide diuretics firstly we need to have a basic understanding of the function of the kidney so to briefly go through those the kidney is made up of about 1 million tiny tubes called nephrons and these nephrons are responsible for filtering and balancing fluid and electrolytes between the blood and the urine now the nephron consists of five main landmarks that you need to be aware of the glomerulus the proximal convoluted tubule the loop of Henle the distal convoluted tubule and the collecting duct and the glomerulus and the convoluted tubules are up in the cortex of the kidney and the loop of Henle and the collecting duct passed down into the medulla of the kidney how it works is water and small molecules are filtered from the blood into what we call the filtrate in the glomerulus and then varying amounts of water and molecules are reabsorbed from the filtrate into the blood along the tubules loop of Henle and collecting ducts and what’s left and the filtrate becomes the urine purpose of understanding thiazide diuretics we’re most interested in the distal tubules and the role of the distal tubule is mainly to control the reabsorption of ions from the filtrate into the blood and water passively follows these ions particularly it follows sodium so when extra sodium is absorbed water follow sit by osmosis looking at the epithelial cells of the distro to Buhl on the inner membrane of the epithelial cells which is what we call the luminal side so the side of the cell that’s facing the lumen of the distal tubule there is a sodium chloride co-transporter molecule and this molecule is responsible for drawing sodium and chloride from the filtrate into the cell and then once they’re in the cell the sodium and chloride then diffuse out to the other side of the cell and are reabsorbed into the blood and this code transport molecule is called a thiazide sensitive sodium chloride cotransporter and it’s the target of action of the thiazide diuretics what the thiazide diuretics do is they work to block the thiazide sensitive sodium chloride co-transporter and this blocks the reabsorption of sodium and chloride from the filtrate into the blood which means that more sodium and chloride is excreted in the filtrate and into the urine because water follow sodium by excreting more sodium water is also excreted so it has a diuretic effect and releases water from the body there’s a few notable side-effects that we need to be aware of since thiazide diuretics result in further excretion of water and electrolytes they can lead to dehydration and subsequently acute kidney injury they can also lead to low chloride levels low sodium levels and low potassium levels the loss of water can also cause a higher concentration of glucose particularly in patients with diabetes it can also raise the level of calcium and uric acid which is animport ant cause of gout in the blood therefore it’s worth using caution when prescribing thiazide diuretics inpatients that have diabetes hypercalcemia or gout and the loss of blood volume can also lead to postural hypotension so when the patient stands up their blood pressure drops so it’s worth being cautious and patients that are older or more frail and have lots of comorbid ditiesso in summary thiazide diuretics block the action of the sodium chloride cotransporter in the distal tubules of the kidney and this results in more sodium chloride and water being excreted in the urine they’re mainly used to treat hypertension but they can also be used to treat edema and they should be used with caution in patients that are frail or have other condition particularly diabetes hypercalcemia and gouts.
