Carbonic anhydrase inhibitors

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Carbonic anhydrase inhibitors

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Questions

USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 32-year-old woman arrives at the outpatient neurologist for a pulsatile headache that is worse in the morning. She also has experienced occasional episodes of vomiting. She has no significant past medical history, and she does not take any medication. Temperature is 37.5°C (99.5°F), blood pressure is 122/70 mmHg, pulse is 68/min., and body mass index is 25 kg/m2. Fundoscopic examination reveals bilateral papilledema. There is no neck stiffness or cranial nerve deficits. Sensation and strength are intact in all extremities. The cardiovascular, pulmonary and abdominal exams are unremarkable. After appropriate workup, the patient is diagnosed with idiopathic intracranial hypertension. She is started on a medication that inhibits carbonic anhydrase. Which of the following laboratory findings best characterizes the adverse effects of this medication?  

External References

First Aid

2024

2023

2022

2021

Acetazolamide p. 251, 568, 624

metabolic acidosis p. 610

in nephron physiology p. 603

pseudotumor cerebri p. 536

site of action p. 625

Adverse effects/events

acetazolamide p. NaN

Altitude sickness p. 686

acetazolamide for p. 624

Glaucoma p. 551

acetazolamide for p. 624

Metabolic alkalosis p. 604, 610

acetazolamide for p. 624

Pseudotumor cerebri p. 536

acetazolamide for p. 624

Transcript

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Diuretics are medications that act on the kidneys to increase production of urine, and to eliminate water, certain metabolic wastes, and electrolytes from the body.

There are 5 main types of diuretics; carbonic anhydrase inhibitors, osmotic diuretics, thiazide and thiazide-like diuretics, loop diuretics, and last but not least, potassium sparing diuretics - which is the only class of diuretic that retains potassium, rather than wastes it.

Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood. The filtered content goes through the renal tubule, where excess waste, and molecules such as ions and water, are removed or filtered through an exchange between the tubule and the peritubular capillaries. So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, and chloride - in order to maintain homeostasis - or the balance of fluid and ions in our body.

The renal tubule has a few segments of its own: the proximal convoluted tubule, the U- shaped loop of Henle, with a thin descending, a thin ascending limb, and a thick ascending limb, and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.

The luminal side of the proximal convoluted tubule is lined by tubule cells, which are also known as brush border cells. The apical surface of these cells, which faces the tubular lumen, is lined with microvilli. Microvilli are tiny projections that increase the cell’s surface area to help it reabsorb more solutes or water.

On the other side is the basolateral surface, which faces the interstitium, or the space between the tubule and the peritubular capillaries. When a molecule of bicarbonate approaches the apical surface of the brush border cell it binds to hydrogen to form carbonic acid. At that point, an enzyme called carbonic anhydrase type 4, which lurks in the tubule among the microvilli like a shark, swims along and splits the carbonic acid into water and carbon dioxide. The overall equation looks like this:

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Hypertension" Nature Reviews Disease Primers (2018)
  5. "Hypertension" Nature Reviews Disease Primers (2018)
  6. "Non-Classical Inhibition of Carbonic Anhydrase" International Journal of Molecular Sciences (2016)
  7. "Carbonic anhydrase inhibitors in patients with respiratory failure and metabolic alkalosis: a systematic review and meta-analysis of randomized controlled trials" Critical Care (2018)
Elsevier

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