Loop diuretic
Encyclopedia
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s that act on the ascending loop of Henle
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...
in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
. They are primarily used in medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
often due to congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
or renal insufficiency. While thiazide
Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.
Mechanism of action
Loop diuretics act on the Na+-K+-2Cl- symporterNa-K-2Cl symporter
The Na-K-Cl cotransporter is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells. There are two varieties, or isoforms, of this membrane transport protein, called NKCC1 and NKCC2. NKCC1 is widely distributed throughout the body; it has important...
(cotransporter) in the thick ascending limb of the loop of Henle
Loop of Henle
In the kidney, the loop of Henle is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its discoverer F. G. J...
to inhibit sodium and chloride reabsorption. This is achieved by competing for the Cl- binding site. Because magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
reabsorption in the thick ascending limb is dependent on sodium and chloride concentrations (primarily on the recycling of the potassium due to the lack of the electropositive gradient generation), loop diuretics also inhibit their reabsorption. By disrupting the reabsorption of these ions, loop diuretics prevent the urine from becoming concentrated and disrupt the generation of a hypertonic renal medulla
Renal medulla
The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the arcuate arterioles. The arcuate arterioles each in turn branch into...
. Without such a concentrated medulla, water has less of an osmotic
Osmotic pressure
Osmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane....
driving force to leave the collecting duct system
Collecting duct system
The collecting duct system of the kidney consists of a series of tubules and ducts that connect the nephrons to the ureter. It participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and antidiuretic hormone.There are several...
, ultimately resulting in increased urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
production. Loop diuretics cause an increase in the renal blood flow by this mechanism. 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 and ameliorate edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
.
Clinical use
Loop diuretics are principally used in the following indications :- edema associated with heart failure, hepatic cirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, renal impairment, nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine.... - hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
- adjunct in cerebralCerebral edemaCerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
/pulmonary edemaPulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
where rapid diuresisDiuresisDiuresis may refer to:* Urine production, as an aspect of fluid balance* Excessive urine production - see polyuria* Immersion diuresis...
is required (IV injection)
They are also sometimes used in the management of severe hypercalcemia in combination with adequate rehydration.
Loop diuretic resistance
Renal insufficiency causes decreased bloodflow to the kidneys, which decreases the glomerular filtration rate (GFR) and reduces the ability of loop diuretics to reach their target organ, the loop of Henle. Similarly, non-steroidal anti-inflammatory drugNon-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s also decrease GFR with comparable results. In patients with reduced GFR, ceiling dosages of loop diuretics are increased proportional to the decrease in GFR. Simultaneous treatment with a thiazide
Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
diuretic such as hydrochlorothiazide
Hydrochlorothiazide
Hydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...
(to inhibit sodium reabsorption at multiple sites in the nephron) is often successful.
Patients with congestive heart failure tend to retain sodium, also necessitating an increase in dosage. The same is true for patients with increased sodium intake.
Adverse effects
The most common adverse drug reactions (ADRs) are dose-related and relate to the effect of loop diuretics on diuresis and electrolyteElectrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
balance.
Common ADRs include: hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
, hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
, hypomagnesemia
Hypomagnesemia
Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
, dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
, gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, postural hypotension, syncope.
Infrequent ADRs include: dyslipidemia
Dyslipidemia
Dyslipidemia or dyslipidaemia is an abnormal amount of lipids in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood, often due to diet and lifestyle. The prolonged elevation of insulin levels can lead to dyslipidemia...
, increased serum creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
concentration, hypocalcemia, rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
.
Ototoxicity
Ototoxicity
Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...
(damage to the ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
) is a serious, but rare ADR associated with use of loop diuretics. This may be limited to tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
and vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
, but may result in deafness in serious cases.
Loop diuretics may also precipitate renal failure in patients concomitantly taking an NSAID and an ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
—the so-called "triple whammy" effect.
Examples of loop diuretics
- FurosemideFurosemideFurosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
- BumetanideBumetanideBumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in people in whom high doses of furosemide are ineffective. It is marketed by Hoffmann-La Roche. The main difference between the two substances is in bioavailability and pharmacodynamic potency...
- Ethacrynic acidEthacrynic acidEtacrynic 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....
- Torsemide
External links
- Loop Diuretic, from the Family Practice Notebook