Loop diuretics

Loop diuretics are primarily used to treat hypertension and oedema often due to congestive heart failure or renal insufficiency. They act on the Na⁺-K⁺-2Cl^- symporter in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. This is achieved by competing for the Cl^- binding site.

By disrupting the reabsorption of ions, the fluid leaving the kidney is more ‘concentrated’ and there is an ‘osmotic driving force’ to dilute it as it leaves the collecting duct system, ultimately resulting in increased urine production and reduction of water in the body.

Because magnesium and calcium reabsorption in the thick ascending limb is dependent on sodium and chloride concentrations, loop diuretics also inhibit their reabsorption.  All this can result in very substantial diuresis – up to 20% of the filtered load of NaCl and water. This is huge when compared to normal renal sodium reabsorption which leaves only ~0.4% of filtered sodium in the urine. 

Like many diuretics, this class of drugs can thus cause electrolyte imbalance, including loss of potassium, calcium, sodium, and magnesium. This loss of minerals affects the nervous system and can also result in reduced bone density – osteoporosis.  The potassium loss is serious and the tendency for all loop diuretics to cause low potassium levels (hypokalemia) has given rise to combination products, either with potassium itself (e.g. Lasix-K) or with the potassium sparing diuretic of amiloride (Co-amilofruse).  The most common adverse drug reactions (ADRs) are thus  - not surprisingly -  related to the effect of loop diuretics on electrolyte balance:

• Dehydration
• Seizures
• Kidney damage
• Lethargy, collapse and coma
• Hyperuricemia
• Gout
• Dizziness and hallucinations
• Postural hypotension, syncope

Loop diuretics cause an increase in the renal blood flow. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.  The collective effects of decreased blood volume and vasodilation decrease blood pressure. 

Ototoxicity is a serious, but rare ADR associated with use of loop diuretics.  Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin and is commonly medication-induced.  [Other ototoxic drugs include antibiotics such as the aminoglycoside gentamicin  and platinum-based chemotherapy agents such as cisplatin. A number of nonsteroidal anti-inflammatory drugs (NSAIDS) such as Meloxicam have also been shown to be ototoxic]. This can result in sensorineural hearing loss, dysequilibrium, or both. Either may be reversible and temporary, or irreversible and permanent.

Loop diuretics may also precipitate renal failure in patients concomitantly taking an NSAID and an ACE inhibitor.

Drugs

This list is likely to change over time, but at least it provides you with an idea of which drugs come within which category.  The drugs which have caused hallucinations according to the ehealthme web site are listed separately under the observations whereas those in this list without any figures have no record on this site.

• Bumetanide [11]  - see detail in observation.

• Furosemide [310] -  see detail in observation

• Etacrynic acid or ethacrynic acid, trade name Edecrin, is a loop diuretic used to treat high blood pressure and the swelling caused by diseases like congestive heart failure, liver failure, and kidney failure.

• Torasemide [13] - or torsemide is used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex and Diuver.

Compared to other loop diuretics, torasemide has a more prolonged diuretic effect than equipotent doses of furosemide and relatively decreased potassium-loss.

Observations

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• Furosemide and Lasix