Thiazide

From Wikipedia, the free encyclopedia

Thiazides are diuretics that are derived from benzothiadiazine. They inhibit Na⁺/Cl^- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. The chemical structure of the original thiazide diuretics contained a thiazide ring system; the term is also used for drugs with a similar action that are not chemically thiazides, such as chlortalidone and metolazone.

Because of their vasodilator properties, Thiazides are often used to treat hypertension. They are the recommended first-line treatment in the US (JNC VII) guidelines and a recommended treatment in the European (ESC/ESH) guidelines. They have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by desensitizing the vascular smooth muscle cells to calcium release induced by norepinephrine (PMID 15611360).

Side effects can include hypokalemia, increased serum cholesterol, and impotence. The side effect of hypokalemia has motivated combining thiazides with ACE inhibitors, which also lower blood pressure but cause hyperkalemia as a side effect. Long-term usage of thiazides is also linked to increased levels of homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis. It is recommended that patients receiving long-term thiazide treatments also receive folic acid supplements to combat the risk.

Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones. This effect is associated with positive calcium balance and is associated with an increase in bone mineral density and reductions in fracture rates attributable to osteoporosis. Because of those properties, they are also used in the treatment of Dent's Disease or idiopathic hypercalciuria.

Thiazide treatment may be combined with ACE inhibitors to increase diuresis without changing plasma potassium concentrations. While ACE inhibitors cause diuresis with potassium retention, thiazide increases potassium excretion. Their combined effects on potassium cancel each other out.

It should be noted that thiazides pass through breast milk, and in some cases, decrease the flow of breast milk. There is no specific information regarding the use of thiazides in children, but it is still advised that mothers avoid using thiazides during the first month of breast feeding.

[edit] Mechanism of hypokalemia

Thiazide-induced hypokalemia (decreased plasma potassium concentration) is partly caused by the direct inhibition of the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and also as a result of activation of the renin-angiotensin system. Decreased sodium reabsorption decreases the sodium gradient the nephron usually uses to reabsorb potassium, resulting in greater potassium excretion. In addition, the increased flow of tubular fluid increases the potassium gradient between the epithelium and lumen, driving the secretion of potassium. Finally, low blood volume induced by diuresis results in activation of the renin-angiotensin system, activating aldosterone, which significantly elevates the secretion of potassium. For this reason, ACE inhibitors, which inhibit angiotensin II production and therefore aldosterone activation, are frequently used in combination with thiazides to combat hypokalemia.