Diuretics: Therapeutic Overview

Indications for diuretics include HTN (the mechanism here isn’t quite understood), edema associated with CHF, and peripheral edema (unrelated to heart failure, often has to do with renal problems). An older term for diuretic was a saliuretic agent (which translates from latin as “promoting sodium excretion”). So diuretics promote both water and sodium loss, and therefore diminish extracellular fluid volume, which reduces BP.


The edema having to do with a patient taking Nifedipine is podo-edema, or foot swelling. A physician can prescribe a diuretic to deal with this drug-induced edema.


Finally, there is pulmonary edema not necessarily associated with heart failure. This is massive amounts of fluid in the lungs, and can greatly diminish the pt’s oxygen exchange. A loop diuretic can be injected intra-venously and within minutes liters of fluid will pour out.


Another use of diuretics is to counter the effects of bloating associated with women’s menstrual cycles, although this is not a primary use for diuretics.


The major goal of diuretics is to increase the excretion of salt and water. These agents are working on the kidney. The thiazide diuretics (this is a chemical class, represented by hydrochlorothiazide as a prototype) have several indications, including osteoporosis—there appears to be a beneficial effect with respect to Ca balance, though it is not very effective. The loop diuretics (furosemide is the prototype) are almost exclusively used for rapidly mobilizing fluid in CHF and severe HTN where the pt has compromised renal function. There seems to be a myth that if you are chemically intoxicated loop diuretics will help to clear the drugs, there are much better ways to detoxify. Potassium sparing diuretics are very weak in promoting Na and water excretion, but they work on the aldosterone receptor and cause retention of potassium. There are many conditions in which hypokalemia (too little potassium) resulting from loop and thiazide diuretics can be corrected by either potassium-rich foods (bananas, apricots) or a potassium sparing diuretic (spironolactone and triamterene are the prototypes). These agents are very seldom prescribed as mono-therapy, but when used with a thiazide, they preserve potassium. The number one product is Diazide (triamterene with hydrochlorothiazide). You won’t see many patients on carbonic anhydrase inhibitors. Unfortunately, on some old exams this enzyme is still mentioned. Osmotic diuretics are used in the acute setting, they must be given via injection. Although they reduce intraocular pressure, the major use in neurology is to cause a shift of fluid out of the cranium to prevent cerebral edema after a stroke. So you wont see pt’s on this type of diuretic.



Loop diuretics act on the thick ascending loop. The thiazides work largely at the distal convoluted tubule. Potassium sparing agents like spironolactone, which are aldosterone receptor blockers, are acting at the cortical collecting tubule. Remember, sodium absorption can occur throughout this pathway, but the loop diuretics will get rid of sodium fast by acting at the main site of sodium absorption, in the thick ascending limb. The downside of loop diuretics is that they can cause life threatening hypokalemia.



Within the loop diuretics there are two subtypes. Type II, which is Furosemide, and Type I, which is Ethacrynic acid. Ethacrynic acid is very seldom prescribed because it has the risk of producing ototoxicity (a favorite national boards question). Among the potassium sparing agents is Spironolactone (aldactone = brand name), which is very seldom prescribed alone. When spironolactone is combined with hydrochlorothiazide the brand name is aldactozide. So if a patient gives you a brand name, don’t just assume that it is a single drug—diazide has two agents in it, aldactozide has two agents, Inderide has two agents (Inderal + hydrochlorothiazide). Whenever you see the suffix “-ide” it is very strong evidence that there is hydrochlorothiazide in it.



The interesting thing about the osmotic diuretics, they are derivatives of isosorbide and mannitol, and clearly their action is to promote water loss by osmotic mechanisms—not by inhibiting any enzyme or tubular transport mechanism.



The carbonic anhydrase inhibitors (Acetazolamide is the prototype) has a sulfur and an amine group… one of the most common allergies is to sulfa-drugs. When a patient presents with a “sulfa allergy”, are they referring to the antibiotic (which was obsolete 50 years ago), or are they referring to the fact that they show a hypersensitivity reaction with the sulfa moiety in their drugs. Sulfa allergies won’t bother you as a dentist too much, just avoid drugs with sulfa moieties to these patients.

Many loop diuretics (furosemide is the prototype), also have a sulfa moiety. Many physicians don’t realize this when they prescribe these drugs. Ethacrynic acid does not contain a sulfa moiety, so this might be advantageous if you need a loop diuretic for a patient with a sulfa allergy.



Loop diuretics are “high-ceiling” diuretics, this term comes from the dose-response curve. As you increase the dose of furosemide, you get a very steep dose response curve and you can continually promote the excretion of sodium. However, with a thiazide there is a small range in which greater dosage will yield a higher response. After a point, additional dose will yield a flat dose response curve; thiazides peak at about 50 mg dosage, there is no further diuretic effect after this and in fact hypokalemia is promoted with higher doses. Always find out the dose when a patient tells you about the drugs that they are on.


Hydrochlorothiazide, the granddaddy of all the thiazide diuretics, has persisted as the drug of choice for step-1 diuretics. It is basically short-acting, although the duration of action on the kidney has nothing to do with its efficacy to mobilize fluid or lower BP. So once a day 25 mg hydrochlorothiazide has effects which long outlast its half-life. There was a time when chlorthalidone was widely recommended, it had a much longer duration of action, but once a day hydrochlorothiazide was just as good. So you don’t see many other thiazides prescribed, aside from hydrochlorothiazide (brand name hydrodiuril).



Thiazide diuretics decrease calcium excretion, unlike the loop diuretics which cause calcium excretion. So the thiazide diuretics can be used to combat osteoporosis. However, the effect compared to calcium supplements is very minimal, although thiazide diuretics can be used theoretically to combat osteoporosis.



When we look at the structure of the potassium sparing agents, we see that they are steroids and closely resemble estrogen. Potassium sparing agents are weak siuretic agent, but very prominent in blocking the aldosterone receptor in the renal tubule collecting duct and therefore potassium is retained. Spironolactone (brand name aldactone) is an aldosterone receptor antagonist. Why would this steroid compete with aldosterone? Because aldosterone is a mineralocorticoid, which has a similar steroid structure. The major use of spironolactone is as a co-agent with hydrochlorothiazide (aldactozide). There are some clinical problems here…

Category: Pharmacology Notes