PEP PAST QUESTIONS QUIZ

DRF focuses on providing essential medicines of assured quality, safety, and affordability, not specifically branded drugs which are often more expensive.

Diphenoxylate/atropine (Lomotil) is an anti-motility agent (an opioid agonist). It is strictly contraindicated in patients with diarrhea caused by Clostridium difficile (pseudomembranous colitis) or other toxin-producing bacteria (like Shigella or Salmonella).

• Mechanism of Harm: In toxin-mediated diarrhea, the body's diarrhea response is a defense mechanism to flush out the bacteria and its toxins. Anti-motility agents paralyze the gut (slow peristalsis), which causes toxin retention.

• Consequence: Retaining the toxins can lead to severe worsening of the colitis, precipitation of toxic megacolon (a life-threatening dilation of the colon), and sepsis.

Why the other options are incorrect

• Cholestyramine: This is a bile acid sequestrant. While it is not a first-line treatment, it has actually been used as an adjunctive therapy in C. difficile because it can bind the toxins (Toxin A and B) produced by the bacteria.

  • Note: It is used with caution because it can also bind the oral vancomycin used to treat the infection, so they must be dosed hours apart. However, it is not absolutely contraindicated in the same dangerous way as anti-motility agents.

• Psyllium: This is a bulk-forming fiber laxative. While adding bulk is not the primary treatment for active infectious colitis, it is not an anti-motility agent and does not carry the same high risk of inducing toxic megacolon.

• Kaolin-pectin: These are adsorbents. They work by binding fluid and potentially bacteria. Like cholestyramine, they are generally not recommended because they are not very effective and can bind antibiotics, but they do not paralyze the gut and are not as dangerous as diphenoxylate.

Ranitidine (an H2-receptor antagonist) is primarily eliminated unchanged by the kidneys. In patients with reduced renal function, the drug can accumulate significantly, leading to an increased risk of side effects, particularly CNS effects like confusion or agitation (especially in the elderly).

• Adjustment Rule: The manufacturer's labeling typically recommends that if the Creatinine Clearance (CrCl) is < 50 mL/min, the dose should be reduced (e.g., to 150 mg once daily) or the dosing interval should be extended. Therefore, a patient with < 30 mL/min definitely requires a dosing adjustment.

Why the other options are incorrect

• Ceftriaxone: Unlike most other cephalosporins, Ceftriaxone has dual elimination (approximately 50% renal and 50% biliary/fecal). Because the liver can compensate for the kidneys (and vice versa), no dosage adjustment is required for renal failure alone (unless there is also severe hepatic dysfunction).

• Pantoprazole: Proton Pump Inhibitors (PPIs) are extensively metabolized by the liver (via the CYP450 system). No dosage adjustment is necessary for renal impairment, including patients on dialysis.

• Metronidazole: This drug is primarily metabolized by the liver. While metabolites may accumulate in severe renal failure, a specific prophylactic dose adjustment for CrCl < 30 mL/min is generally not required in the standard labeling (though it may be modified for hemodialysis schedules)

CYP2C19