Diuretics are drugs that promote diuresis; a process that leads to increased production of urine. The purpose of every diuretic is to promote water loss.
Of course, there are many types of diuretic – including thiazide diuretics. Here though, we focus on loop diuretics. Loop diuretics achieve their diuretic effect by acting on the ascending limb of the loop of Henle; a part of the nephron named after the acclaimed German physician and anatomist, Friedrich Gustav Jakob Henle (1809-1885).
Over the course of this guide, we review their mechanism of action, side effects and drug interactions. We also take some time to review important clinical considerations. First, let’s take a few minutes to learn more about the primary indications of loop diuretics.
Edema is the common thread that weaves its way through each indication. Edema refers to the accumulation of fluid in certain parts of the body. The more fluid build-up, the more “swelling” manifests.
If you’re unfamiliar with the basic physiology of the nephron, we recommend taking a few moments to learn more about the structure and function of this feature. The four basic functions of the nephron include:
Knowing these processes is essential to properly understand how any diuretic works.
Loop diuretics act on the thick ascending limb of the loop of Henle. Along this limb, these drugs inhibit a protein responsible for sodium, potassium and chloride transport – a protein called the Na+/K+/2Cl– transporter.
More specifically, loop diuretics compete with the Cl– site of the transporter – reducing reabsorption of the above ions – with water following by osmosis. It’s precisely this water loss that contributes to the therapeutic value of loop diuretics.
However, loop diuretics also work by a secondary mechanism – namely, dilatation of capacitance veins; an effect which reduces preload and enhances the contractile ability of cardiac muscle.
Both effects – water elimination and vasodilation – combine to generate the therapeutic potential of loop diuretics. The above mechanism of loop diuretics directly contributes to its side effect profile.
When we talk about the clinical pharmacology of loop diuretics, we need to think about the following factors:
Loop diuretics are associated with their own range of potential side effects.
More seriously, loop diuretics are also linked to ototoxicity. Because the endolymph of the inner ear is also regulated by a similar transporter, loop diuretics may impact electrolyte balance in the ear and lead to tinnitus, vertigo and deafness.
Loop diuretics continue to play an important clinical role in the treatment of edematous states.
Knowing how they work, what side effects and drug interactions they have, and how these facts implicate therapeutic matters, is an absolute must for every student.