Question

13. Diuretics! (8 points total)
A. For each of the following different medications below, explain how they work to promote diuresis. I might suggest including a sketch (of probably a nephron) and indicating specific “location of action” in your answers, and a cellular-level detail of drug action.    Use an additional sheet of paper for your answers if necessary. 2 pts each
B. Which one of these (a, b, or c) can most directly lead to the dangerous condition of hyperkalemia? Why/how? 2 pts

a. Thiazide diuretic (ie. Chlorothiazide/Diuril)

b. Furosemide/Lasix
c. Spironolactone

Answer 1

1. A diurectic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. All diuretics increase the excretion of water from bodies. It is used to treat heart failure, liver cirrhosis, hypertension, influenza, water poisoning, and kidney diseases.

Thiazide Diuretic

It acts on the distal convoluted tubule and inhibit the sodium-chloride symporter leading to retention of water in the urine, as water normally follows penetrating solutes. Frequent urination is due to the increased loss of water that has not been retained from the body as a result of concomitant relationship with sodium loss from the convoluted tubule.

Cellular level action

Thiazide blocks the sodium-chloride channel in the proximal segment of the distal convoluted tubule. When the Na/Cl channel is blocked, decreased level of sodium cross the luminal membrane, thus decreasing the action of sodium-potassium (Na/K) pump and decreasing Na and water passage to the interstitium.

Furosemide

It is a loop diurectic. It may cause a substantial diuresis—up to 20% of the filtered load of NaCl and water. It inhibit the body’s ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine, where as water normally follows sodium back into the extracellular fluid.

It acts by inhinbiting the luminal Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle, by binding to the chloride transport channel, thus causing sodium, chloride, and potassium loss in urine.

Spironolactone

It is a potassium-sparing diuretics.which do not promote the secretion of potassium into the urine. Spironolactone is a aldosterone antagonists. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal scells, preventing sodium reabsorption.

2. Potassium-sparing diuretics such as spironolactone has the potential to cause hyperkalemia. This risk is increased when used in association with potassium supplements and salt substitutes, as previously noted. The risk of hyperkalemia with spironolactone increases threefold if used with potassium supplements.