Thiazide
Thiazides are
diuretics, a class of
drug that promote water loss from the body. 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.
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. They may 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 treaments also receive
folic acid supplements to combat the risk.
Thiazides also lower urinary calcium excretion. That is why they are used to prevent 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.
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.
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.
*
U.S. National Library of Medicine: Diuretics, Thiazide
