What are Diuretics and How do they Work?

Welcome to this video about diuretics – before we get into the details of diuretics, let’s go over a brief review of the Anatomy and Physiology of the kidney:

• Kidney’s primary function is to regulate the volume, composition, and pH of body fluids
• The normally functioning kidney retains substances needed by the body and eliminates those not needed by way of urine.
• The nephron (pic) is the functional unit of the kidney – each kidney contains approx. 1 million nephrons.
• The nephron is made up of a glomerulus and a tubule.
• The glomerulus being a network of capillaries and the tubule being a structure of epithelial cells that is divided into 3 main segments – the proximal tubule, loop of Henle, and distal tubule, each differing in structure and function.

The nephron has 3 primary functions:

• Glomerular filtration
• Tubular reabsorption
• Tubular secretion (Last) Urinary excretion

Glomerular filtration is 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 refers to the movement of substances from the tubule to the blood in the peritubular capillaries.

Tubular secretion indicates movement of substances from blood in the peritubular capillaries to glomerular filtrate flowing through the tubules.

DIURETICS are drugs that increase the excretion of water, sodium, and other electrolytes through the kidneys, thereby increasing urine formation and output.

• Diuretics are given to manage edema, heart failure, and hypertension.
• Diuretics act at different sites in the nephron.
• Their job is to ↓ reabsorption of Na+ and water, and to ↑ urine output, therefore often referred to as a “water pill.”

There are 3 main classes of diuretics:

• Thiazide Diuretics
• Loop Diuretics
• Potassium-sparing Diuretics

There are 2 additional types that are not used as frequently, but I’ll mention briefly:

• Carbonic anhydrase inhibitors
• Osmotic Diuretics

Thiazide diuretics

• Most commonly used diuretic
• Hydrochlorothiazide (a.k.a. HCTZ) is the most common thiazide drug used.
• Given for long-term management of heart failure and hypertension.
• They work by ↓ reabsorption of Na+, water, and chloride in the distal convoluted tubule.
• Thiazides are not strong diuretics because most sodium is reabsorbed before it reaches the distal convoluted tubule and only a small amount is reabsorbed at this site.
• Thiazide diuretics are well absorbed and accumulate only in the kidneys.
• Diuretic effect usually begins at 2 hrs and lasts 6-24 hrs.
• Thiazide diuretics are synthetic drugs that are chemically related to the sulfonamides, so they must be used cautiously in patients allergic to sulfonamide drugs.

Loop diuretics
The diuretic of choice when rapid effects are required and when renal function is impaired.

• They inhibit Na+ and Cl- reabsorption in the ascending limb of the loop of Henle (where reabsorption of most filtered Na+ occurs).
• Loop diuretics are the most effective and versatile diuretics available for clinical use.
• Furosemide (Lasix) is the most commonly used loop diuretic
• Furosemide is given for edema and hypertension
• It can be given PO, 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 slow IV push. It is also given IV for acute renal failure and hypertensive crisis.

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 are usually given in combination with a thiazide like HCTZ that is a potassium-losing diuretic.
• A major adverse effect of these drugs is hyperkalemia (too much potassium) – so patients should not be given potassium supplements, or eat foods high in potassium, or use salt substitutes (which contain KCl rather than NaCl).

Potassium-sparing diuretics include:

• Spironolactone – blocks the sodium- retaining effects of aldosterone
• Amiloride and Triamterene – both act directly on the distal tubule to ↓ the exchange of sodium for potassium.

Now the 2 not-so-common diuretics I mentioned:
Carbonic anhydrase inhibitors

• The weakest of the diuretics and rarely used in cardiovascular disease.
• Primary use is in the treatment of glaucoma.

Drugs in this class include:
acetazolamide and methazolamide

Osmotic diuretics

• Inhibit the reabsorption of water and sodium and produce rapid diuresis
• They are given IV
• Common example is Mannitol – useful in treating oliguria or anuria and may prevent acute renal failure during a prolonged surgery or trauma.

Adverse effects of diuretics:
Major adverse effects are fluid and electrolyte imbalances.

• Most frequent problem with thiazide and loop diuretics is hypokalemia (K < 3.5), sometimes requiring treatment with potassium supplements.
• Thiazide and Loop diuretics = hypokalemia

• Potentially serious side effect of potassium-sparing diuretics is hyperkalemia (K > 5), which may lead to cardiac dysrhythmias.
• Potassium-sparing diuretics = hyperkalemia

 
Other adverse effects of potassium-losing diuretics (thiazides and loop diuretics) include:

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

Drugs that increase effects of diuretics:

• Aminoglycoside antibiotics
• Antihypertensive drugs
• Corticosteroids

Drugs that decrease effects of diuretics: