Diuretics

Diuretics promote the excretion of water and electrolytes by the kidneys. They are used in the treatment of heart failure or in hepatic, renal, or pulmonary disease when salt and water retention has resulted in oedema or ascites. Diuretics are also used, either alone, or in association with other agents, in the treatment of hypertension. The principal groups of diuretics are thiazides, ‘Loop’ or ‘high – ceiling’ diuretics، potassium sparing diuretics, osmotic diuretics, Mercurial diuretics and carbonic anhydrase inhibitors. Thiazides such as Hydrochlorothiazide are used to relieve oedema due to chronic heart failure and in lower doses, to reduce blood pressure. Loop diuretics such as frusemide are used in pulmonary oedema due to left ventricular failure and in patients with chronic heart failure. Osmotic diuretics raise the osmolality of plasma and renal tubular fluid. They are used to reduce or prevent cerebral oedema, to reduce raised intra-ocular pressure, and in acute renal failure. Although loop diuretics are the most potent their duration of action is relatively short, whilst thiazide diuretics are moderately potent but produce diuresis for a longer period. Potassium – sparing diuretics such as Spironolactone have a relatively weak diuretic effect and are normally used in conjunction with thiazide or loop diuretics. Adverse effects: The adverse effects of diuretic therapy are mainly due to the fluid and electrolyte imbalance induced by the drugs. Hyponatraemia is an adverse effect of all diuretics. The risk of hypokalaemia, which may occur with Both thiazide and loop diuretics, depends more on the duration of action than on potency and is thus greater with thiazides than with loop diuretics (when given in equipotent doses). Potassium-sparing diuretics can cause hyperkalaemia. Other electrolyte disturbances include hypercalcaemia (thiazides), hypocalcaemia (loop diuretics) and hypomagnesaemia (thiazide and loop diuretics).

• Thiazaides and Related Diuretics:

Thiazides and related compounds are moderately potent diuretics; they act within 1-2 hours of oral administration and most have duration of action 12-24 hours; they are usually administered early in the day so that diuresis does not interfere with sleep.

Hydrochlorothiazide

Indications: Edema, Hypertension, Peripheral Edema due to Chronic Heart Failure, And Pulmonary Edema Due To Chronic Heart Failure.

Contraindications: Anuria, Gout, Hepatic Coma, Hyperuricemia, Hypokalemia, Hypomagnesemia, Hyponatremia, Neonatal Hyperbilirubinemia, Oliguria, And Severe Renal Disease.

Dose and Administration: Hypertension: Orally, Adult, 12.5, 25 mg daily; elderly initially 12.5 mg daily. Oedema, Orally, Adult, initially 25 mg daily on rising increasing to 50 mg daily if necessary, elderly initially 12.5 mg daily. Severe Oedema in patients unable to tolerate loop diuretics, by mouth، Adult، up to 100 mg either daily or on alternate days (maximum 100 mg daily). Nephrogenic diabetes insipidus, by mouth daily.

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Indapamide:

Indications: Edema, Hypertension.

Contraindications: Anuria, Dehydration, Oliguria, And Severe Renal Disease. Dose and Administration: tablet (1.25 mg) by oral route once daily in the morning.

• Loop Diuretics:

Furosemide/Frusemide:

Indications: -for the treatment of oedema, oliguria due to renal failure; mild to moderate hypertension, usually in combinations with other antihypertensive agents and as adjunct in the treatment of hypertensive crisis and for the treatment of hypercalcemia.

Contraindications: patients with precomatose states associated with liver cirrhosis, renal failure with anuria.

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Dose and Administration:Oedema: Orally Adult, initially 40 mg daily on rising, maintenance, 20, mg daily or 40 mg on alternate days, may be increased to 80 mg daily in resistant oedema; Child 1 – 3 mg/Kg body weight daily (maximum 40 mg daily). Acute Pulmonary Oedema: by slow intravenous injection, Adult, 20-50 mg، if necessary increase by 20 mg steps every 2 hours, if effective single dose is more than 50 mg, consider using slow intravenous infusion at a rate not exceeding 4 mg/minute, child 0.5-1.5 mg/kg body weight daily (maximum 20 mg daily). Oliguria (glomerular filtration rate less than 20 ml/minute): by slow intravenous infusion of a rate not exceeding 4mg/minute, Adult, initially  over 1 hour; if urine output not satisfactory during hour after first dose, infuse 500 mg over 2 hours then, if no satisfactory response during hour after second dose, infuse 1 g over 4 hours; if no response after third dose, dialysis probably necessary. Hypertension: Orally – initially 40mg two times a day; the dosage being adjusted according to patient’s need. Intravenously, hypertensive crisis in patients with normal renal function, IV 40 to 80mg. . Antihypercalcemic – Orally, 120mg a day a single dose or divided into two or three doses; IM or IV, Adult, 80-100mg in severe cases, the dosage being repeated if necessary every one to two hours until the desired response is obtained. In less severe cases smaller doses may be given every two or four hours. Child, IM or IV, To to 50mg, the dosage being repeated if necessary every four hours until the desired response is obtained.

BUMETANIDE:

Indications: is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome.

Contraindications: hypovolaemia, dehydration, severe hypokalaemia, severe hyponatraemia; comatose or precomatose states associated with liver cirrhosis; renal failure due to nephrotoxic or hepatotoxic drugs, anuria

Dose and Administration: the usual total daily dose is 0.5-2mg as a single dose.

• Potassium Sparing Diuretics:

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Spironolactone:

Indications: Aldosteronism, Ascites, Chronic Heart Failure, Diagnostic Test for Primary Aldosteronism, Edema, Edema due to Hepatic Cirrhosis, Edema due to Nephrotic Syndrome, Hypertension, Hypokalemia Prevention, Peripheral Edema due to Chronic Heart Failure, Pulmonary Edema due to Chronic Heart Failure. Contraindications: Acute Renal Disease, Anuria, Hyperkalemia, Severe Renal Disease, Dehydration, Hyperchloremic Acidosis, Hyponatremia, and Hypovolemia Dose and Administration: 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia, when oral potassium supplements or other potassium-sparing regimens are considered inappropriate.

• Osmotic Diuretics:

Mannitol:

Indications: Mannitol is used to increase urine production (diuretic). It is used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). This medication is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. This drug may also be used, along with other diuretics, to help remove certain drugs/poisons from the body (e.g., aspirin, barbiturates, bromides, carbon monoxide)

Contraindications: congestive cardiac failure, pulmonary oedema

Dose and Administration: The usual adult dosage ranges from 50 to 200 g in a 24-hour period, but in most instances an adequate response will be achieved at a dosage of approximately 100 g/24 hours. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 mL/hr.

• Carbonic anhydrase inhibitors:

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Acetazolamide:

Indications For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure.

Contraindications: hypokalaemia, hyponatraemia, hyperchloraemic acidosis; severe hepatic impairment; renal impairment; sulphonamide hypersensitivity

Dose and Administration: Glaucoma: Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple (open-angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg.