Different types of diuretics and appropriate uses

A diuretic is any substance that increases urine excretion of both water and electrolytes. They are more commonly known as 'fluid tablets'. Diuretics have different clinical uses depending on their sites and mechanisms of action. There are a number of different subclasses of diuretics for a range of different purposes.

Thiazides

Diuretics known as Thiazides are predominantly used in low doses of the treatment of hypertension, or occasionally in combination with loop diuretics to treat severe heart failure. Examples of thiazides include bendroflumethiazide and hydrochlorothiazide, and when taken orally their onset will typically occur within 1-2 hours of administration. The duration of their action depends on the drug, with bendroflumethiazide typically lasting for 6-12 hours and other drugs such as chlortalidone lasting for a longer period of time (between 24-72 hours).

Loop Diuretics

Loop diuretics are regularly used for the symptomatic treatment of heart failure, as well as fluid retention in chronic kidney disease (CKD), and examples include frusemide, torasemide, and bumetanide. They are fast acting, with rapid onset of dieresis commonly less than one hour after being administered orally. They act for approximately 6 hours, so many patients take doses throughout the day as part of their prescription.

Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors such as acetazolamide are often used for glaucoma, and also for the prophylaxis (prevention) of altitude sickness (off prescription).

Osmotic diuretics

Osmotic are used in a hospital setting for the treatment of cerebral oedema.

Potassium sparing diuretics

Potassium sparing diuretics such as triameterene are used in the treatment of hypertension, heart failure, and oedema of liver failure. These diuretics are generally weaker than the other categories, and they include the commonly used spironolactone and eplerenone which are also known medically as aldosterone antagonists.

How are diuretics prescribed?

How diuretics are prescribed will most often depend on a combination of the disease that is being treated, specific patient characteristics, medical history, and any particular medication that the patient is currently taking.

Hypertension

The most commonly used first line treatment for hypertension is a calcium channel blocker diuretic (CCBs). However, if certain medicines or further medical conditions contraindicate the prescription of CCBs, such as heart failure (or a high risk of heart failure), a thiazide such as indapamide has been evidenced to be safer and more effective (1).

Indapamide, used on its own or in conjunction with another diuretic such as perindopril, has been evidenced to be particularly effective for patients aged 80 or above. A 2008 study, published in the New England Journal of Medicine, revealed that this particular treatment combination for hypertension reduced all-cause mortality, heart failure and stroke with limited adverse effects (2). Further possible contraindications that need to be considered in the prescription of diuretics for hypertension include high levels of potassium and poorly functioning kidneys with low levels of estimated glomerular filtration rate (eGFR).

Acute left ventricular failure (LVF)

Frusemide, administered intravenously, has been evidenced to offload the pulmonary oedema that causes the breathlessness associated with LVF. The chemical process catalysed by the diuretic results in a rapid initial action that relieves breathlessness through pulmonary vasodilation, with the diuretic effect kicking in later. Eplerenone can also be used as an additional diuretic in the event of a heart attack, with its use evidenced to reduce both the length of hospital stay and total days of heart failure hospitalisation when administered according to prescribing guidelines (3).

Whilst diuretics are widely considered and evidenced for the reduction of pulmonary oedemas, it is recommended that they are not used for idiopathic oedema as the initial benefit can be offset and compromised by tolerance and a worsening of the swelling (4).

Diuretics commonly used in combination

Many diuretics are used together to increase their efficacy and improve patient outcomes, as well as averting well known side effects of diuretics used in isolation.

Where refractory heart failure has been evidenced to respond poorly to an isolated loop diuretic, the use of an accompanying thiazide has been shown to improve clinical symptoms (5). However, such a combination can also result in a range of other health conditions such as dehydration, hyponatremia, and hypokalaemia and must be administered under very careful specialist supervision.

Safer and more widely used combinations include potassium-sparing diuretic and loop diuretics (beneficial for patients who have, or are at risk of developing hypokalaemia) and spironolactone and loop diuretics (for patients on loop diuretics also at risk of developing hypokalaemia).

Some combination products are prescribed fairly regularly, although the rationale for doing so is not always clear: many guidelines advise against this, as many combinations are not required for clinical purposes. Such an example would be the prescribing of amiloride for heart failure patients, which is almost always never required due to patients also regularly taking an ACE-inhibitor which has a potassium sparing effect and as such does not require diuretic combinations (6).

Who should avoid using diuretics

Diuretics should not be used under any circumstances in pregnant women due to the risk of foetal/neonatal toxicity, and both thiazides and loop diuretics can significantly precipitate or worsen pre-existing gout. Instead of diuretics, beta blockers and methyldopa are to treat hypertension in pregnancy, and allopurinol is the only recommended diuretic for gout if there are no other treatment options available.

Many elderly patients must only take lower dose diuretics due to the potential for renal complications or the risk of oedema.

The use of diuretics in patients with severe liver disease is also contraindicated, as hypokalaemia can result in hepatic coma. Only in the treatment of cirrhosis are certain diuretics allowed (most often spironolactone), and only under specialised supervision.

References

1. Izzo JL Jnr (2012) Value of combined thiazide-loop diuretic therapy in chronic kidney disease: heart failure and renin-angiotensin-aldosterone blockade J Clin Hypertens 14(5):344
2. Beckett NS, Peters R, Fletcher AE, et al (2008) Treatment of hypertension in patients 80 years or older N Engl J Med 358(18):1887-98
3. Gheorghiade M, Khan S, Blair JE, et al (2009) The effects of eplerenone on length of stay and total days of heart failure hospitalization after myocardial infarction in patients with left ventricular systolic dysfunction. Am Heart J 158(3):437-43
4. Richards D, Aronson J. Oxford Handbook of Practical Drug Therapy OUP: Oxford, UK.
5. Barzilay JI, Davis BR, Cutler JA, et al (2006) Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Arch Intern Med 166(20):2191-201
6. NICE Clinical Knowledge Summary (CKS): Heart Failure – chronic. Available online at http://cks.nice.org.uk/heart-failure-chronic (last accessed 2nd June 2015)