Thiazide Diuretics

Thiazide diuretics, especially hydrochlorothiazide, are widely used in the treatment of hypertension.  Thiazide diuretics work by inhibiting the sodium/chloride cotransporter that is located in the luminal membrane of the tubules of the ascending loop of Henle and the distal convoluted tubule.  The sodium/chloride cotransporter is used to remove (reabsorb) sodium from the tubules.  Inhibition of the cotransporter results in decreased sodium and water reabsorption, which results in lower blood pressure. Over time, blood pressure effects seem to result from arteriolar smooth muscle relaxation and decreased peripheral vascular resistance.   These medications also result in decreased calcium excretion, which reduces risk of developing calcium oxalate stones in patients with kidney stones.  Thiazide diuretics are derived from sulfites, so avoid use in sulfa allergic patients.

Class Drugs

• Chlorothiazide

• Chlorthalidone

• Hydrochlorothiazide

• Indapamide

• Metolazone

Class Mechanism of Action

Inhibition of the Sodium/Chloride (Na/Cl) co-transporter in luminal membrane of tubules in the ascending loop of Henle and distal convoluted tubule

• Decreases reabsorption of Na

• Results in increased concentration of Na and Cl in tubules

• Must be secreted into tubules for action to function

Limited efficacy in patients with renal dysfunction and in those using NSAIDS (decreased renal blood flow)

• Results in loss of potassium (K), secondary to Na/K exchange in distal tubule

• Results in loss of magnesium (Mg)

• Results in calcium re-absorption (decreased Ca excretion)

Arteriolar dilation

• Reduces afterload

• Unknown mechanism

Renal Tubule - Primary sites of action of diuretics.

Class Applications

Hypertension

• Initially, reduces blood volume, resulting in decreased cardiac output and lower blood pressure

• Long-term, causes arteriolar smooth muscle relaxation, resulting in decreased peripheral vascular resistance

• Total ceiling effect exists, limits utility of increasing doses

Heart Failure

• Adjunct to loop diuretics

Hypercalciuria

• Reduces formation of kidney stones (calcium oxalate)

Diabetes insipidus

• Substitutes for ADH, reducing hypo-osmolar urine output

Class Adverse Effects

• Hypokalemia

• Hyponatremia

• Hyperuricemia

• Volume depletion

• Hypercalcemia

• Hyperglycemia

• Derived from sulfites

Do not use in patients with sulfa allergy

Drug Table

Drug Name	Application	Comments	Image
Chlorothiazide			"Clorox" "Tide"
Chlorthalidone			"Clorox" "Hal" "Done"
Hydrochlorothiazide			"Hydrant" "Clorox" "Tide"
Indapamide			"India" "Pam"
Metolazone			"Metal" "Zone"