Diuretics, thiazide

Figure 46-1. The nephron is the functional unit of the kidney. Note the various tubules, the site of most diuretic activity. The loop of Henle is the site of action for the loop diuretics. Thiazide diuretics ad at the ascending portion of the loop of Henle and the distal tube of the nephron.

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

Diuretics Thiazides diuretics, loop diuretics Produce polyuria... 

Diuretics Thiazides Loop diuretics K+-sparing diuretics Hydrochlorothiazide Furosemide Amiloride 44 4 4... 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

A friend of mine is concerned about his 78 years old mother who has recently been to her doctor for an annual health check up. He is worried because at his mothers last visit her blood pressure had risen to 160/90 and she was prescribed an antihypertensive, a diuretic (thiazide). The medication is giving her a lot of problems due to the diuretic effect, and because of arthritis of the knees she moves slowly and this make it difficult for her to reach the bathroom in time. She has now developed urinary incontinence due to her medication. 

The thiazide diuretics possess antihypertensive properties, in part consequent upon electrolyte and plasma-volume changes but mainly resulting from a direct cardiovascular depressant effect. This is clearly illustrated by the non-diuretic thiazide, diazoxide, which is an effective hypotensive [326b, c]. It is not therefore, surprising that both these properties should be found (in varying proportions) in other, structurally related, compounds. One particular line of research, aimed at modification of the thiazide heterocycle (the o-chlorobenzenesulphonamide moiety was untouched as it was believed essential to activity-the subsequent advent of ethacrynic acid questions this belieO examined first the corresponding... 

Diuretics - Generally initiate therapy with a thiazide or other oral diuretic. Thiazide-type diuretics are drugs of choice hydrochlorothiazide or chlorthalidone are generally preferred. Reserve loop diuretics for selected patients. This therapy alone may control many cases of mild hypertension. Consider treating diuretic-induced hypokalemia (less than 3.5 mEq/L) with potassium supplementation or by adding a potassium-sparing diuretic to therapy. 

Diuretics (thiazide, Heart failure Gout Pregnancy... 

Table 1.13. Most diuretics are designed to deal with conditions of edema by reducing the reabsorption of chlorides, sodium, and water as these are the major constituents of edema fluid. Diuretics are grouped into five main categories loop diuretics, thiazides, potassium-sparing diuretics, osmotic diuretics, and carbonic...

The electronic structures of hydrochlorothiazide 146 and related substances have been determined by the complete neglect of differential overlap (CNDO/2) method (83AF688). The calculation confirms that the diuretic thiazides are electron-accepting, whereas diazoxide 147, a non-... 

Thiazide Diuretics. Thiazide drugs share a common chemical nucleus as well as a common mode of action. These drugs act primarily on the early portion of the distal tubule of the nephron, where they inhibit sodium reabsorption. By inhibiting sodium reabsorption, more sodium is retained within the nephron, creating an osmotic force that also retains more water in the nephron. Since more sodium and water are passed through the nephron, where they will ultimately be excreted from the body, a diuretic effect is produced. Thiazides are the most frequently used type of diuretic for hypertension. Specific types of thiazide drugs are listed in Table 21-3. 

Diuretics work by increasing the amount of sodium and fluids excreted by the kidneys. Less fluid means less total blood volume and improved circulation and blood pressure. There are five main classes of the drug loop diuretics, thiazide diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. 

Many diuretic agents (loop diuretics, thiazides, amiloride, and triamterene) exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (spironolactone). 

Among the diuretics, thiazides are particularly recommended for treatment of hypertension. To avoid undue loss of K combination with triamterene or amiloride is often advantageous. 

AMIODARONE CARBONIC ANHYDRASE ANTAGONISTS, LOOP DIURETICS, THIAZIDES Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia Monitor potassium levels eveiy 4-6 weeks until stable, then at least annually... 

MEXILETINE DIURETICS-CARBONIC ANHYDRASE INHIBITORS, LOOP DIURETICS, THIAZIDES Effect of mexiletine 1 by hypokalaemia Uncertain Normalize potassium levels before starting mexiletine... 

SOTALOL DIURETICS-CARBONIC ANHYDRASE INHIBITORS, LOOP DIURETICS, THIAZIDES t risk of ventricular arrhythmias, particularly torsades de pointes ventricular tachycardia, caused by sotalol Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels eveiy 4-6 weeks until stable... 

TOREMIFENE DIURETICS-THIAZIDES Risk of hypercalcaemia Additive effect Monitor calcium levels closely. Warn patients about the symptoms of hypercalcaemia... 

CICLOSPORIN LOOP DIURETICS, THIAZIDES Risk of nephrotoxicity Additive effect Monitor renal function weekly... 

ALLOPURINOL DIURETICS-THIAZIDES Possible t risk of severe allergic reactions when allopurinol is given with thiazides in the presence of renal impairment Uncertain Caution in co-administering allopurinol with thiazides in the presence of renal insufficiency... 

CALCIUM DIURETICS-THIAZIDES Risk of hypercalcaemia with high-dose calcium 1 renal excretion of calcium by thiazides Monitor calcium levels closely... 

SCREENING FOR ABUSE OF DIURETICS Benzothiadiazine diuretics (thiazides) may be abused by patients who are obsessed with losing weight prolonged use can cause severe hypokalae-mia and hypomagnesaemia. 

Beta blockers, diuretics Thiazide diuretics Calcium channel blockers, alpha blockers ACE inhibitors, ARBs... 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

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