DESCRIPTION
A benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the
MECHANISM
is comparable.
CATEGORIES
Antihypertensive Agents,Diuretics,Sodium Chloride Symporter Inhibitors
CHEMICAL FORMULA
C16H16ClN3O3S
COMPOSITION
Indapamide 1.5 mg
INDICATION
For the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.
PHARMACODYNAMICS
Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.
MECHANISM
Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2.
ABSORPTION
Rapidly absorbed from gastrointestinal tract.
METABOLISM
Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
ELIMINATION
Indapamide is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
HALF LIFE
14 hours (biphasic)
TOXICITY
Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness
FOOD INTERACTIONS
Take without regard to meals. Magnesium, potassium and zinc needs increased.
SIDE EFFECTS
Low potassium levels. Signs include feeling tired, weak, numbness, or tingling; muscle cramps; hard stools (constipation); throwing up; or a fast heartbeat. Feeling dizzy. Rise slowly over a few minutes when sitting or lying down. Be careful climbing. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Feeling tired or weak.