What are Diuretics and How do they Work?

Are you interested in learning about diuretics and how they can affect the human body? Today we’re going to dive into what this class of drugs does, and why they might may be prescribed to a patient. Let’s get started!

Diuretics work with the kidneys to help the human body remove salt and water, and are often used to reduce blood pressure. Before we get into the details of exactly how diuretics work, let’s go over a brief review of the anatomy and physiology of the kidney.

The kidney’s primary function is to regulate the volume, composition, and pH of body fluids through the formation of urine. Normally functioning kidneys retain substances needed by the body and eliminate those not needed through urine.

Nephrons

Each kidney contains approximately 1 million nephrons, which serve as the functional units of the kidney responsible for filtering. Each nephron is made up of a microscopic glomerulus and a tubule.

The glomerulus is a network of capillaries which filter blood, and the tubule is a structure made of epithelial cells that return necessary substances to blood and remove wastes.

The nephron has 3 primary functions:

• Glomerular filtration
• Tubular reabsorption
• Tubular secretion

Glomerular filtration occurs when arterial blood enters the glomerulus at a high pressure, and the water, electrolytes, and other solutes are pushed out of the capillaries into the Bowman’s capsule and on to the proximal tubule. Tubular reabsorption occurs during the movement of substances from the tubule to the blood in the peritubular capillaries. Tubular secretion is the movement of substances from blood in the peritubular capillaries to glomerular filtrate flowing through the tubules.

Now, let’s talk about diuretics and how they can affect the kidneys.

How Diuretics Affect the Kidneys

Diuretics increase the excretion of water, sodium, and other electrolytes through the kidneys, thereby increasing urine formation and output. Sometimes called “water pills,” diuretics are prescribed to treat edema, hypertension, and heart failure.

Types of Diuretics

There are three three main types of diuretics, each acting at different sites of the nephron:

• Thiazide diuretics
• Loop diuretics
• Potassium-sparing diuretics

The first type, thiazide diuretics, are the most commonly used diuretic, and hydrochlorothiazide (also known as HCTZ) is the most common thiazide drug used. This type of diuretic is typically prescribed for long-term management of heart failure and hypertension.

These diuretics work by decreasing reabsorption of sodium, water, and chloride in the distal convoluted tubule, or DCT. Thiazides are not considered strong diuretics because most sodium is reabsorbed before it reaches the DCT, and only a small amount is actually reabsorbed at this site.

Thiazides are well-absorbed and accumulate only in the kidneys, and the diuretic effect usually begins after two hours and lasts 6 to 24 hours. One contraindication for thiazide diuretics is that they are synthetic drugs that are chemically related to sulfonamides, so they must be used cautiously in patients allergic to sulfonamide drugs.

The second type, loop diuretics, are the treatment of choice when rapid effects are required and when renal function is impaired. They inhibit sodium and chloride reabsorption in the ascending limb of the loop of Henle, where reabsorption of most filtered sodium and chloride occurs.

Loop diuretics are the most effective and versatile diuretics available for clinical use. Furosemide (also called Lasix) is the most commonly used loop diuretic and is prescribed for edema and hypertension. It can be given orally, with dosage gradually increased to obtain adequate diuretic or antihypertensive response. If it’s necessary to remove the edema quickly, furosemide may be given by a slow IV push. It is also given intravenously for acute renal failure and hypertensive crisis.

The third type, potassium-sparing diuretics, act at the distal tubule to decrease sodium reabsorption and potassium excretion.

Potassium-sparing diuretics are weak diuretics when used alone, so they are usually given in combination with a thiazide like HCTZ.

A major adverse effect of these drugs is hyperkalemia (too much potassium), so patients should not be given potassium supplements, eat foods high in potassium, or use salt substitutes (which contain potassium chloride rather than sodium chloride).

Potassium-sparing diuretics include:

• Spironolactone: blocks the sodium-retaining effects of aldosterone
• Amiloride and triamterene: both act directly on the distal tubule to decrease the exchange of sodium for potassium

Adverse Effects

It’s important to be aware of the potential adverse effects of diuretics. For all types of diuretics, the major adverse effects are fluid and electrolyte imbalances.

The most frequent problem with thiazide and loop diuretics is hypokalemia (potassium level of under < 3.5 mEq/L), sometimes requiring treatment with potassium supplements. Other adverse effects of these potassium-losing diuretics include:

• Loss of sodium chloride, magnesium, and bicarbonate, which also occurs with diuresis
• Changes in serum and urinary calcium levels.
• Dehydration
• Hyperglycemia
• Elevated serum uric acid
• Ototoxicity (hearing impairment or loss, tinnitus, and dizziness)

A potentially serious side effect of potassium-sparing diuretics is hyperkalemia (potassium level of > 5 mEq/L), which may lead to cardiac dysrhythmias.

There are drugs that increase effects of diuretics, such as aminoglycoside antibiotics, antihypertensive drugs, and corticosteroids.

Drugs that decrease effects of diuretics include NSAIDs (like ibuprofen or aspirin), oral contraceptives, and vasopressors such as epinephrine and norepinephrine.

It’s very important that patients are advised to tell their doctors they are taking diuretics before starting another medication.

All right, I hope this review of kidney anatomy and the effect of diuretics has been helpful. Thanks for watching, and happy studying!