Quiz 32: Diuretic Therapy and the Pharmacotherapy of Renal Failure
Spironolactone inhibits aldosterone by binding to its receptors in distal tubule and collecting ducts of nephron. The angiotensin II indirectly affects sodium reabsorption and thereby induces the adrenal cortex to synthesize and secrete additional amounts of aldosterone hormone. The drug acts as a potent diuretic and induces mild diuresis. It also has no or less effect on excretion of potassium. The rate of morbidity, mortality, and dysrhythmias associated with heart failure has been shown to be reduced when using the drug.
Drug excretion is the elimination of the drugs from the body. The principle organ of excretion is the kidney. The other systemic types of drug excretion are • Biliary excretion • Pulmonary excretion • Salivary excretion • Gastrointestinal excretion • Genitourinary excretion • Dermal excretion The drug administered exists in two forms bound and unbound form. The unbound form is the free form of the drug. The unbound drugs are small in size and can easily get filtered by the kidneys. In the kidneys this unbound drugs get infiltered in the glomerullar filtration. Thus the free form of the excess drugs gets eliminated in the kidneys. The binding character of the drug is the one of the factor that affects the renal excretion. Drugs that are bound to plasma proteins behave as macromolecules and cannot be filtered through glomerulus. The protein bound drugs are in inactive form and have long half life. The process of drug elimination by metabolism and drug excretion is delayed. Hence a drug by binding to the plasma proteins remains inactive and also acquires macro size which affects the elimination of the drug and the drug remains for longer period in the body.
Diuretics are drug that increases the rate of urine that is impaired in patients with renal failure, hypertension, pulmonary edema, heart and liver failure. They act by reducing the sodium ion re-absorption by nephrons and thus excreting more sodium in the urine. Loop diuretics acts by preventing the reabsorption of sodium and chloride by blocking the ionic symporter in the henle's loop of the nephron. Treatment with this drug exerts excessive fluid leading to loss of electrolytes, leading to fluid electrolyte imbalance. Thiazide type diuretics acts on distal tubule and decreases the reabsorption of sodium ions, resulting in less water absorption and excretion of more fluids. The treatment of this also leads to loss of electrolytes like sodium and potassium. The medication using this drug leads to electrolyte imbalance such as hypochloremia, hypomagnesemia, hypokalemia and hyponatremia. In case diuretics like potassium - sparing diuretics, the drug acts by inhibition of the alsosterone, excreting water and sodium increases and potassium is retained. These kinds of diuretics maintain the electrolyte balance, but can cause adverse effects when potassium levels in the body increases. Osmotic diuretics act by creating an osmotic gradient by means of mannitol which when administered intravenously. The sugar is filtered by the kidney, but cannot be reabsorbed thus creating an osmotic gradient. This gradient decreases the reabsorption of sodium and water resulting in increased amount of urine. Electrolyte imbalance may occur in both the ways and proper care must be provided while prescribing the drug.