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4. Cimetidine

Cimetidine is a potent inhibitor of the P-glycoprotein (PGP) efflux pump (4). PGP efflux pumps are found throughout the GI tract as well as in the blood brain barrier. Loperamide is a substrate with considerable affinity for the PGP pump. With therapeutic doses of loperamide, the bioavailability is around 0.3%, and plasma loperamide is 97% protein bound (inactive). After absorption from the GI tract, the remaining non-protein-bound loperamide must then pass through the second layer of PGP pumps in the BBB. Loperamide then enters the CNS, where it exhibits opioid agonistic effects. PGP inhibitors such as cimetidine can drastically reduce the quantity of loperamide capsules needed to ingest in order to create opioid agonist effects.

Black cohosh is known to cause numerous metabolic drug interactions through inhibition or induction of most major CYP enzyme pathways, but it is not associated with significant PGP inhibition. Bismuth subsalicylate, omeprazole and aspirin would not be expected to increase CNS dose of loperamide.

What is the best treatment for a patient suffering from loperamide toxicity? (Click on the correct answer to be directed to the fifth of seven pages)

  1. Amiodarone
  2. Calcium gluconate
  3. Magnesium sulfate
  4. Overdrive pacing
  5. Sodium bicarbonate

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