Diuretics Flashcards
What is a diuretic?
A diuretic is any compound that causes the excretion of an increased volume of urine from the body. More accurately, it is a drug that increases the excretion of both fluids (water) and solutes (e.g., Na+).
How do diuretics act?
Most diuretics increase the excretion of Na+ and water by the kidneys. They either have a direct action on the cells of the nephron or modify the content of the filtrate. The reabsorption of Na+ from the filtrate is inhibited, leading to increased Na+ excretion. Water loss is secondary to Na+ excretion.
When do we use diuretics?
Diuretics are used in various conditions associated with fluid retention. Some of these conditions include chronic heart failure, chronic liver disease (cirrhosis), chronic kidney disease, nephrotic syndrome, pre-menstrual edema, leg venous insufficiency, hypertension, glaucoma, raised intra-cranial pressure, and to increase excretion of drugs or Ca2+.
How does water act as a diuretic?
Under normal conditions, increased water intake leads to an increase in the volume of urine excreted. This process is controlled by antidiuretic hormone (ADH), the most important hormone regulating water balance. ADH is secreted from the posterior pituitary in response to changes in serum osmolality. Normally, some ADH is present in the circulation, maintaining urine volume at approximately 1.5 L/day. However, this can be adjusted in various ways, such as the effects of alcohol or nicotine.
What happens when there is reduced expression of AQP2 channels in the DCT and Collecting Duct cells?
Reduced expression of AQP2 channels on the apical surface of DCT (Distal Convoluted Tubule) and Collecting Duct cells leads to more water excretion. As a result, urine production increases, and less water is reabsorbed back into the bloodstream. This results in reduced levels of ADH in the blood.
How do alcohol and nicotine affect ADH release and urine volume?
Alcohol inhibits ADH release, leading to an increase in urine volume. On the other hand, nicotine and morphine increase ADH release, which reduces urine volume.
What is the role of demeclocycline in treating SIADH?
Demeclocycline acts as an ADH antagonist in the collecting ducts. It is used for the treatment of the syndrome of inappropriate ADH (SIADH), a condition characterized by excessive ADH secretion. By blocking ADH action, demeclocycline helps to reduce water reabsorption in the collecting ducts.
What is the function of tolvaptan?
Tolvaptan is an ADH V2 receptor antagonist. It is used as a second-line treatment for SIADH. By blocking the V2 receptors, tolvaptan inhibits the effects of ADH and helps to increase urine volume.
What is the role of caffeine as a diuretic?
Caffeine, found in coffee, tea, and cola, is a weak diuretic. It increases cardiac output and dilates the afferent renal arteriole, leading to an increase in glomerular filtration rate (GFR) and subsequent urine production.
What are the different parts of the nephron involved in fluid reabsorption?
The nephron consists of the glomerulus, Bowman’s capsule, proximal tubule (70% reabsorption), loop of Henle (20% reabsorption), distal tubule (5% reabsorption), and collecting duct (4% reabsorption). The glomerular filtration rate (GFR) is approximately 180 L/day, but only 1% of the filtrate becomes urine.
What are examples of carbonic anhydrase inhibitors?
Acetazolamide is an example of a carbonic anhydrase inhibitor
What are examples of osmotic diuretics?
Mannitol is an example of an osmotic diuretic.
What are examples of loop diuretics?
Furosemide and Bumetanide are examples of loop diuretics.
What are examples of thiazide diuretics?
Bendroflumethiazide, Indapamide, Hydrochlorothiazide, and Chlortalidone are examples of thiazide diuretics.
What are examples of potassium-sparing diuretics?
Spironolactone, Eplerenone, and Amiloride are examples of potassium-sparing diuretics.
Where do most diuretics act?
Most diuretics (but not all) are secreted into the proximal tubule and act from the luminal (urine) side of the tubule.
What are the different segments of the nephron where diuretics act?
Diuretics can act on various segments of the nephron, including the proximal tubule, descending and ascending limbs of the loop of Henle, distal tubule, and collecting ducts.
How do loop diuretics work at a molecular level?
Loop diuretics act on the Na/K/2Cl cotransporter (NKCC2) in the thick ascending limb of the Loop of Henle. They block the Cl- channel of the cotransporter, resulting in increased loss of Na+, K+, Cl-, and water.
What are the main uses of loop diuretics?
Loop diuretics are much more powerful than other diuretics and are used to clear peripheral edema. They are also administered intravenously for acute pulmonary edema. Furosemide, also known as ‘Lasix,’ is a commonly used loop diuretic with an effect that lasts for approximately 6 hours.
What are some side effects associated with loop diuretics?
Side effects of loop diuretics include dehydration, renal impairment, hypokalemia (low levels of K+), hyponatremia (low levels of Na+), hypocalcemia (low levels of Ca2+), hypomagnesemia (low levels of Mg2+), hyperuricemia (elevated uric acid levels causing gout), and auditory nerve damage (especially with high doses and renal impairment), also known as ‘ototoxicity.’ The loss of Na+/K+ and Ca2+/Mg2+/Cl- is associated with these side effects.
What is the main cause of hypokalemia associated with loop diuretics?
Loop diuretics increase Na+ delivery to the distal tubule, where it is exchanged for K+. This exchange of Na+ for K+ leads to increased excretion of K+ in the urine, which is the main cause of hypokalemia associated with loop diuretics.
How do loop diuretics and thiazide diuretics differ in terms of molecular action?
Loop diuretics act by blocking the Na/K/2Cl cotransporter in the thick ascending limb of the Loop of Henle, while thiazide diuretics act by blocking the Na/Cl cotransporter in the distal convoluted tubule.
What are the main effects of thiazide diuretics?
Thiazide diuretics inhibit the apical Na/Cl co-transporter in the distal tubule, leading to increased loss of Na+, K+, Cl-, and water. However, thiazide diuretics are much less powerful than loop diuretics. They are commonly used for the treatment of mild edema or hypertension. Thiazide diuretics have a longer duration of action, up to 24 hours. Bendroflumethiazide is an example of a thiazide diuretic, which is available in generic form and is relatively inexpensive.
How does Na+/K+ exchange occur in the distal tubule?
In the distal tubule, Na+ and Cl- are reabsorbed via the apical Na+/Cl- co-transporter. This increases the Na+ concentration in the tubular cells. Na+ is then exchanged for K+ on the basolateral side of the tubular cells. The K+ is subsequently excreted in the urine, contributing to the hypokalemia observed with loop diuretics.
