Diuretics Research Paper

The simplest definition of diuretics is that they are chemical agents that increase the rate of urine formation and out flow 1. By this process, they lead to increased excretion of electrolytes such as sodium and chloride ions. Also, they increase water secretion from the body. The kidneys are the primary target organ for diuretics where they interfere with reabsorption of electrolytes from the Lumina of the nephrons 2, the functional unit of kidney. Each kidney contains about one million nephrons, each capable of forming urine separately. The kidneys of healthy adult can handle up to 1200ml/minute of blood flow 1,2.

Diuretics are widely used for treatment of edematous conditions resulting from various causes such as nephrotic

increase in Ca levels and hypersensitivity reaction.2,3 There are many classes of Diuretics such as loop diuretics, potassium sparing, thiazide, osmotic diuretics. They are classified according to mechanism of action, site of action, chemical class and effect on urine electrolytes. Each class vary widely in its efficacy.1,2 At the 16th century, calomel (mercurrous chloride) was used as diuretic, but its poor absorption from the GIT limited its use and was replaced by the organomerrcurials(chlormerodin) which was highly effective, but unfortunately its parenteral use and possibility of toxicity and tolerance limited their use and they are no longer used, so scientists searched for more safe and effective

Loss of C=C bond at third and fourth position increase the potency to 3-10 overlap. Substitution at position 4,5 or 8 with alkyl groups ordinarily lessens diuretic action and position 2 can tolerate a small alkyl group such as -CH3.4,5 The mechanism of action of thiazide is not fully understood but they act by inhibition of NaCl reabsorption in the cortical portion of the thick ascending limb of loop of Henle & Distal tubule and also inhibit electroneutral Na & Cl co-transport system. they are rapidly absorbed orally and have volume of distribution equal or greater than the body weight. They are strongly bound to plasma proteins so most of them are not metabolized but excreted as they are in urine as chlorothiazide and hydrochlorothiazide, but benzthiazide, bendroflumethazole and polythiazide are extensively metabolised.1,2The onset of most thiazides occurs after 2-3 hours. they have half life time nearly 8-12 hours permitting one dose per day.4,6 Thiazide diuretics were available at the end of 1950 when they had acceptable adverse effect. There are many drugs in this class of diuretics discussed in the following table. Each drug has its own characteristics according to side chains.