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Chapter: Modern Medical Toxicology: Cardiovascular Poisons: Diurets, Antihypertensives and Antiarrhythmics

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Potassium Sparing Diuretics - Cardiovascular Poison

Potassium sparing diuretics interfere with reabsorption of sodium at the distal tubule, thereby decreasing potassium secretion.

Potassium Sparing Diuretics

Potassium sparing diuretics interfere with reabsorption of sodium at the distal tubule, thereby decreasing potassium secretion. Examples include amiloride, eplerenone, triamterene, and spironolactone. Amiloride and triamterene act by blocking sodium channels in the luminal membrane of principal cells in the late distal tubule and collecting duct, while spironolactone competitively inhibits the binding of aldosterone to mineralo-corticoid receptors.

The major therapeutic use of potassium sparing diuretics is in the treatment of oedema or hypertension, in combination with other diuretics so as to offset the latters’ kaluretic (or potassium excreting) effect. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism.

Drug Interactions

·      Co-administration of potassium sparing diuretics with ACE inhibitors is associated with an increased risk of severe hyperkalaemia.

·              Amiloride used with other diuretics may produce hyponatraemia and hypochloraemia.

·      Severe hyponatraemia may occur when triamterene and chlorpropamide are concomitantly administered.

Adverse Effects and Toxic Features

·      The most dangerous adverse effect is hyperkalaemia.

·      Cardiovascular abnormalities secondary to hyperkalaemia include bradycardia, conduction defects, sinus arrest, and hypotension. Cardiovascular symptoms have only been reported after chronic therapy and not from an acute inges-tion. Tall, peaked T waves or T-wave elevations compared with previous tracings, lowered R waves, increased depth of the S wave, widening or absence of the P wave, progres-sive widening of the QRS complex, prolongation of the PR interval, and/or depression of ST segment have been associated with ECG changes of hyperkalaemia.

·      Weakness, areflexia, and fatigue may be noted secondary to hyperkalaemia from chronic therapy.

·      There can also be effects related to the gastrointestinal (vomiting, diarrhoea), CNS (headache, drowsiness, confu-sion, vertigo), musculoskeletal (leg cramps), and dermato-logical (skin rashes), systems. Metabolic acidosis can occur with hyperkalaemia.

·      Spironolactone can cause peptic ulceration, gynaecomastia, impotence, and hirsutism, and menstrual irregularities and breast soreness in females. There are indications that it may be carcinogenic.

·      Angina pectoris and myocardial infarction have occurred in patients treated with eplerenone.

Treatment

·      Patients should be monitored for fluid status and serum elec-trolytes (particularly sodium and potassium). Administer 0.9% saline as needed.

·      Monitor vital signs and ECG in symptomatic patients, particularly in patients with significant electrolyte abnor-malities.

·      Consider administration of activated charcoal after a poten-tially toxic ingestion.

·      Treat severe hyperkalaemia (associated arrhythmias, QRS widening) aggressively. Monitor ECG continuously during and after therapy.

o     Calcium chloride: Adult: 5 ml IV bolus of a 10% solu-tion over 5 minutes; Child: 0.2 to 0.3 ml/kg of a 10% solution over 5 to 10 minutes (20 to 30 mg/kg/dose).

o     Sodium bicarbonate: Adult or Child: 1–2 mEq/kg IVbolus.

o     Insulin/dextrose: Adult: 5 to 10 units regular insulinIV bolus with 100 ml of D50 IV immediately; monitor serum glucose every 30 minutes. Child: 0.5 to 1 gm/ kg dextrose as D25 or D10 IV followed by 1 unit of regular insulin for every 4 grams of dextrose infused; monitor serum glucose every 30 minutes.

o     Sodium polystyrene sulfonate: Adult 15 to 60 ml by nasogastric tube or rectal enema; Child: 1 gm/kg by nasogastric tube or rectal enema.

·              If hypotension is not corrected by treatment of hyper-kalaemia, infuse 10 to 20 mg/kg of isotonic fluid and place

Forensic Issues (All Diuretics)

Despite the widespread use of diuretics in medical practice, acute overdoses involving these agents are fortunately quite rare. Most reported cases of toxicity are actually related to chronic use. Long-term diuretic use to treat hypertension has recently been associated with the development of type 2 diabetes.

 

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