**Question:** A patient is on long term ketoconazole therapy. He developed gastroesophageal reflux disease (GERD). Which of the following drug should not be used for treatment of GERD in this patient?

A. Omeprazole
B. Pantoprazole
C. H2-receptor antagonist (e.g., cimetidine)
D. Antacid

**Correct Answer:** C. H2-receptor antagonist (e.g., cimetidine)

**Core Concept:**
Long-term ketoconazole therapy can lead to achlorhydria, which is the absence of gastric acid secretion. As GERD is primarily treated by increasing gastric acid secretion, using a drug that inhibits gastric acid secretion, like H2-receptor antagonists (cimetidine), is not advisable in this scenario.

**Why the Correct Answer is Right:**
Long-term ketoconazole therapy interferes with the normal physiological process of gastric acid production, resulting in achlorhydria. This condition necessitates the use of medications that increase gastric acid secretion, such as proton pump inhibitors (PPIs) like omeprazole and pantoprazole.

**Why Each Wrong Option is Incorrect:**
A. Omeprazole: Proton pump inhibitors (PPIs) are used to increase gastric acid secretion, which is beneficial in achlorhydric conditions like GERD. Omeprazole is a suitable choice for treating GERD in this context.

B. Pantoprazole: Similar to omeprazole, pantoprazole is also a proton pump inhibitor (PPI) that increases gastric acid secretion, making it a suitable choice for treating GERD in this context.

C. H2-receptor antagonists (e.g., cimetidine): As mentioned earlier, H2-receptor antagonists like cimetidine are used to reduce gastric acid secretion, which is counterproductive in achlorhydric conditions like GERD. The use of cimetidine would not be effective for treating the patient's GERD.

D. Antacids: Antacids neutralize gastric acid, providing temporary relief from symptoms but do not address the underlying issue of achlorhydria. The use of antacids would not be an appropriate treatment for the patient's GERD.

**Clinical Pearls:**
1. In achlorhydric conditions like GERD, it is essential to choose medications that increase gastric acid secretion, such as PPIs like omeprazole and pantoprazole.
2. H2-receptor antagonists, like cimetidine, are ineffective for treating GERD in achlorhydric conditions.
3. Antacids provide temporary relief but do not address the underlying issue of achlorhydria, and therefore are not suitable for treating GERD in this context.
4. It is crucial to consider the patient's underlying condition (achlorhydria from long-term ketoconazole therapy) when choosing a therapeutic agent for GERD treatment.