Diuretics: Carbonic Anhydrase Inhibitors

Front 1

List carbonic anhydrase inhibitors

Back 1

Acetozolamide
Dichlorophenamide
Methazolamide

Front 2

Tubular site of action of acetozolamide

Back 2

Proximal convoluted tubule

Front 3

MOA of Carbonic Anhydrase Inhibitors

Back 3

At the luminal surface of PCT, we have a Na-H antiporter. Carbonic anhydrase is an enzyme found both in the tubular fluid and the interstitium. The enzyme is responsible for providing the Hyrogen ions to enable the antiporter.

Front 4

Are carbonic anhydrase inhibitors often used as diuretics?
What are they used for?

Back 4

No, as diuretics they are used rarely.
Major uses are:
Tx of glaucoma
Urinary alkalinization to enhance the secretion of uric acid. This also enhances the secretion of weak acids such as aspirin. These effects are short in duration. NaHCO3 is needed to maintain the alkaline state of the urine.
Also used as tx in the mountain acute sickness (severe symptoms of pulmonary or cerebral edema)

Front 5

The bottom line of the effects of the carbonic anhydrase inhibition

Back 5

Increased excretion of HCO3
Decreased excretion of H ions.

Front 6

What other diuretics decrease H secretion?

Back 6

K-sparing diuretics

Front 7

Lack of aldosterone has what 3 effects

Back 7

Decreased reabsorption of Na
Decreased K excretion
Decreased H secretion
so ECF volume contraction, hyperkalemia and metabolic acidosis

Front 8

In hypoaldosteronism, the ECF volume contraction elicits the release of ADH. How is it inappropriate in this case?

Back 8

Because ADH causes increased water reabsorption, which farther dilutes the sodium and make the hyponatremia even more severe.

Front 9

In adrenal insufficiency, what are the effects of hypocortisolinemia

Back 9

Increased secretion of ACTH
So we get hyperpigmentation (pro-opiomelanocortin)

Front 10

Acidosis increases cortisol excretion by the adrenal. How does cortisol correct the situation?

Back 10

Cortisol acts on the kidney to increase transcription of the Na-H antiporter and Na-3HCO3 symporter genes in the proximal tubule. So in other words, with high cortisol, we retain more Na and excrete more H ions. Explains the edema formation with hypercorisolenemia-associated states!