The video contains a simple and visual explanation of how ‎Canagliflozin ‎Empagliflozin and Dapagliflozin, SGLT2 inhibitors, work to get the kidneys to excrete glucose into the urine. We cover some basics about how the nephron works and look in detail at the action of SGLT2 inhibitors on the sodium-glucose transport protein 2 (SGLT2) in the proximal tubule. We also talk about the indications and adverse effects.
Hi this is tom from zero finals comm in this video i’m going to be explaining how sglt2 inhibitors work now sglt2 inhibitors are used in type 2 diabetes to help to reduce the blood sugar levels they differ slightly from most anti-diabetic drugs which work by either increasing the insulin in the body or increasing the insulin sensitivity of the cells of the body
And the objective of increasing the insulin or the insulin sensitivity is to get the body to take more glucose out of the blood and to store it in the tissues and that’s how they reduce blood sugar levels however in sglt2 inhibitors they work slightly differently they work by causing the kidneys to excrete glucose into the urine and by excreting glucose into the
Urine you reduce the amount of glucose or sugar that’s in the blood and the rest of the body for this video i’ll give you three examples the first is dapper glyph losen the second is canna glyph losen and the third is mpeg allah frozen and if you remember these three you’re unlikely to come across very many others but the clue is that all of them end with glyph
Losen there’s only one real indication for these medications and that’s type 2 diabetes let’s go through the mechanism of action firstly in order to understand how sglt2 inhibitors work we need a very basic understanding of the function of the kidneys so let’s go through that briefly so to briefly go through those the kidneys 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 for the purpose of understanding sglt2 inhibitors we’re most interested in the proximal tubule glucose is actively reabsorbed in the proximal tubule along with sodium normally glucose is filtered passively into the filtrate in the glomerulus and under normal conditions all of this
Glucose is reabsorbed in the proximal tubule so you shouldn’t find any glucose in the urine where the blood glucose exceeds about ten millimoles per liter then the proximal tubular enough capacity to reabsorb all of it so you’ll start to see glucose appearing in the urine let’s look a little bit closer at the proximal tibial there are cells that line the proximal
Tubule that have a molecule called the sodium glucose linked transporter which we shortened to s gl t on their luminal side this transports sodium and glucose together across the cell membrane and out of the filtrate this sodium and glucose then passively diffuses out of the other side of the cell into the interstitial fluid where it’s reabsorbed into the blood
This sodium glucose linked transporter is a target of the sglt2 inhibitors such as dapa glyph losen and as the name suggests they inhibit the action of the sglt2 molecule and prevent the glucose that has filtered out of the blood in the glomerulus from being reabsorbed and as a result the glucose is secreted into the urine and the blood glucose stays low because
It’s not being reabsorbed in the proximal tubule and this is how they reduce blood sugar and reduce the amount of sugar in the body let’s look at the side effects so as you would imagine one of the main side effects is glucose area and this is glucose in the urine and that’s because this is the main mechanism of action of these medication the second side effect is
Increased rate of urinary tract infections increasing the amount of sugar in the urine provides a great environment for bugs to grow therefore it does increase the risk of urinary tract infections and candida infections which we commonly call thrush another side effect is weight loss and this is because when you excrete a lot of glucose in the urine this can cause
An osmotic diuresis which means that the high level of glucose and the filtrate draws water into the urine through osmosis so the water is moving from the area of low concentration of solutes into the area of high concentration of solutes meaning a lot of glucose in the urine and this causes the person to lose more glucose in the urine and to lose more water in the
Urine which leads to frequent urination dehydration low blood pressure and weight loss the final and quite rare complication is diabetic ketoacidosis notably with only moderately raised glucose levels and this is quite a rare complication but it’s one that’s worth knowing about firstly for your exams and secondly so you can bear it in mind when you start seeing
Patients who are on these medications so thanks for watching i hope you found this video helpful if you did don’t forget there’s plenty of other resources on the zero to finals website including loads and loads of notes on various different topics that you might cover in medical school with specially made illustrations there’s also a whole test section where you
Can find loads of questions to test your knowledge and see where you’re up to in preparation for your exams there’s also a blog where i share a lot of my ideas about a career in medicine and tips on how to have success as a doctor and if you want to help me out on youtube you can always leave me a thumbs up give me a comment or even subscribe to the channel so
That you can find out when the next videos are coming out so i’ll see you again soon
Transcribed from video
How does Dapagliflozin work? Understanding SGLT2 inhibitors. By Zero To Finals
