Thiazide and loop diuretics

Domenic A. Sica, Barry Carter, William Cushman, Lee Hamm

Research output: Contribution to journalReview article

90 Citations (Scopus)

Abstract

Key Points and Practical Recommendations: Although chlorthalidone and hydrochlorothiazide are structurally similar, they are very different pharmacokinetically, with chlorthalidone having both an extremely long half-life (approximately 40 to 60hours) and a large volume of distribution, with gradual elimination from the plasma compartment by tubular secretion. Furosemide usage, the most widely used diuretic in the loop diuretic class, can be complicated by extremely erratic absorption, with a bioavailability range of 12% to 112%. Chlorthalidone, at a dose of 25mg, is comparatively more potent than 50mg of hydrochlorothiazide, particularly as related to overnight blood pressure reduction. In ALLHAT, there was no difference among chlorthalidone, amlodipine, lisinopril, and doxazosin for the primary outcome or mortality. Secondary outcomes were similar except for a 38% higher rate of heart failure with amlodipine; a 10% higher rate of combined cardiovascular disease, a 15% higher rate of stroke, and a 19% higher rate of heart failure with lisinopril; and a 20% higher rate of cardiovascular disease, a 20% higher rate of stroke (40% higher rate in blacks), and an 80% higher rate of heart failure with doxazosin, compared with chlorthalidone. The ACCOMPLISH study may affect future practice guidelines as a result of its findings favoring the amlodipine/benazepril combination; however, the generalizability to patient populations with a lesser cardiovascular risk profile remains in question and the dose of hydrochlorothiazide was only 12.5mg to 25mg daily, which was a dose lower than that used in placebo-controlled trials using hydrochlorothiazide. Certain low-renin patient groups (eg, blacks, the elderly, and diabetics) as well as those who manifest the metabolic syndrome are commonly more responsive to thiazide-type diuretic therapy. Diuretics can be successfully combined with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, centrally acting agents, and even calcium channel blockers. Although thiazide-type diuretics are among the best-tolerated antihypertensive agents in terms of symptomatic adverse effects, diuretic-related adverse side effects include those with established mechanisms (eg, such as electrolyte changes and/or metabolic abnormalities) and other side effects, which are less well understood mechanistically (eg, impotence), although the latter is not universally accepted as a diuretic-related side effect. Thiazide-induced hypokalemia is associated with increased blood glucose, and treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent diabetes. Thiazide-induced hyperuricemia occurs as a result of volume contraction and competition with uric acid for renal tubular secretion, but does not necessarily contraindicate using a thiazide, especially if a uric acid-lowering drug such as allopurinol is being used. Adverse interactions include the blunting of thiazide effects by nonsteroidal anti-inflammatory drugs and the potential to increase fatigue, lethargy, and increase in glucose when combined with β-blockers. Thiazide-type diuretics are useful first-line agents in the treatment of hypertension because they have been proven to reduce cardiovascular mortality and morbidity in systolic and diastolic forms of hypertension and do so at low cost. Loop diuretics should not be used as first-line therapy in hypertension since there are no outcome data with them. They should be reserved for conditions of clinically significant fluid overload (eg, heart failure and significant fluid retention with vasodilator drugs, such as minoxidil) or with advanced renal failure and can be combined with thiazide-type diuretics.

Original languageEnglish (US)
Pages (from-to)639-643
Number of pages5
JournalJournal of Clinical Hypertension
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2011

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Chlorthalidone
Sodium Potassium Chloride Symporter Inhibitors
Thiazides
Sodium Chloride Symporter Inhibitors
Hydrochlorothiazide
Diuretics
Amlodipine
Heart Failure
Doxazosin
Lisinopril
Hypokalemia
Hypertension
Uric Acid
Cardiovascular Diseases
Stroke
Minoxidil
Hyperuricemia
Lethargy
Allopurinol
Glucose Intolerance

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Thiazide and loop diuretics. / Sica, Domenic A.; Carter, Barry; Cushman, William; Hamm, Lee.

In: Journal of Clinical Hypertension, Vol. 13, No. 9, 01.09.2011, p. 639-643.

Research output: Contribution to journalReview article

Sica, Domenic A. ; Carter, Barry ; Cushman, William ; Hamm, Lee. / Thiazide and loop diuretics. In: Journal of Clinical Hypertension. 2011 ; Vol. 13, No. 9. pp. 639-643.
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