Diuretics - Carbonic Anhydrase Inhibitors

Question 1

What are examples of this class of medications?

Answer 1

1. Oral drugs: acetazolamide
2. Topical drugs: brizolamide and dorzalamide

Question 2

Where is the site of action of those drugs?

Answer 2

They work on the proximal convoluted tubules.

Question 3

What is their MOA?

Answer 3

They work by inhibiting carbonic anhydrase; this leads to multiple effects:

1. In the kidneys; the blockage of carbonic anhydrase leads to increased sodium, potassium and bicarbonate excretion which leads to water excretion (diuretic effect which is weaker than other diuretics like loop diuretics)
2. In the eyes; the blockage of carbonic anhydrase leads to decreased formation of bicarbonate ions which decreases the formation of aqueous humors thereby decreasing IOP
3. In the CNS; the blockage of carbonic anhydrase leads to decreased formation of CSF

Question 4

What are the therapeutic uses of carbonic anhydrase inhibitors?

Answer 4

1. Treatment of open-angle glaucoma: they work by inhibiting the formation of bicarbonate (by blocking carbonic anhydrase enzyme) which prevents the formation of aqueous humor which decreases the intraocular pressure. It should be mentioned that they may only be used for chronic cases of glaucoma.
2. Prophylaxis of mountain sickness; acetazolamide can be used in prophylaxis for acute mountain sickness in healthy individuals who rapidly ascend above 10,000 ft (3000m) which could lead to hypoxia and its associated symptoms (nausea, weakness, tiredness as well as cerebral and pulmonary edema) so the medication is given 5 days prior to the ascent (MOA; the medication decreases the pH in the brain by inhibiting bicarbonate formation which increases the respiratory rate which is why it can also be used for sleep apnea)
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3. Edematous states; it can be used to treat edematous states like pulmonary edema and ascites when the patients suffer from alkalosis
4. Alkalinazation of urine; which decreases the likelihood of cystine stone and goat formation

Question 5

What are the side effects of carbonic anhydrase inhibitors?

Answer 5

A. Renal side effects:
1. Potassium wasting: these medications increase water & sodium excretion in the collecting tubule which leads to potassium excretion
2. Kidney stone formation: these medications increase calcium and phosphate excretion, which can form stones in the alkaline environment that the medications also cause.

B. Systemic side effects:
1. Metabolic acidosis and a subsequent hypochloremia.
2. High doses can lead to dizziness and paresthesia

Question 6

What are the contraindications of this medication?

Answer 6

Patients with hepatic cirrhosis because they cause ammonia retention within the body, which can lead to hepatic encephalopathy