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Review Question - QID 210619

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QID 210619 (Type "210619" in App Search)
A 52-year-old woman makes a follow-up appointment with her primary care physician for evaluation of her diabetes medications. Specifically, she complains that she has been experiencing flushing, nausea, and palpitations after drinking a glass of wine with dinner after she started the latest regimen for her diabetes. She was warned that this was a side-effect of one of her medications but she did not understand the severity of the reaction. Given this experience, she asks to be placed on an alternative regimen that does not involve the medication that caused this reaction. Her physician therefore replaces the medication with another one that interacts with the same target though at a different binding site. Which of the following is a side-effect of the new medication?

Hepatotoxicity

13%

20/157

Lactic acidosis

13%

20/157

Pancreatitis

16%

25/157

Urinary tract infection

3%

4/157

Weight gain

54%

84/157

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This patient with a disulfiram-like reaction to alcohol is most likely taking the sulfonylurea drug class for diabetes. Meglitinides also target ATP-gated potassium channels and have a side effect of weight gain.

Glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP. This increase in ATP closes ATP-gated potassium channels and thereby leads to depolarization of the β cells and subsequent release of insulin. Both sulfonylureas and meglitinides work by binding to and closing these ATP-gated potassium channels, though the two drugs bind to different sites on the channel. Side effects of sulfonylureas include a disulfiram-like reaction to alcohol, and side effects of meglitinides include weight gain.

Incorrect Answers:
Answer 1: Hepatotoxicity is a side effect of thiazolidinediones; however, these drugs do not interact with ATP-gated potassium channels.

Answer 2: Lactic acidosis is an important side effect of biguanides such as metformin; however, these do not interact with ATP-gated potassium channels.

Answer 3: Pancreatitis is a side effect of GLP-1 analogs such as exenatide; however, these do not interact with ATP-gated potassium channels.

Answer 4: Urinary tract infections are a complication of SGLT-2 inhibitors such as canagliflozin; however, these do not interact with ATP-gated potassium channels.

Bullet Summary:
Meglitinides and sulfonylureas both stimulate insulin release through binding to ATP-gated potassium channels.

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