Drug-Nutrient Interactions

Question 1

Delivery Environment
Gastric emptying is a rate-controlling step for absorption, and any nutrient or drug that alters gastric emptying will affect pharmacokinetic parameters. The rate of nutrient and drug absorption typically follows the direction of change in gastric emptying. Slow gastric emptying slows absorption and rapid gastric emptying increases the absorption rate.

Answer 1

Factors assoc w/ Delayed Gastric Emptying Formula Related:

1. Long-chain fats - high conc - ↓ gastric motility
2. PRO - high conc - ↓ gastric motility
3. pH - low conc - ↓ gastric motility and ↑ small bowel motility
4. Osmolarity (mOsm/L) - 800 - ↓ gastric and ↑ small bowel motility.
5. Viscosity - high - ↓ gastric motility
6. Volume - Large - ↓ gastric motility and ↑ small bowel motility

Question 2

Rapid gastric emptying accompanied w/ rapid GI transit can result in poor absorption bcuz there is too little contact between drugs or nutrient and the absorptive surface of the bowel.

Answer 2

Use of short and long-term jejunal feeding using both hydrolyzed and intact protein formulations suggests that delivery beyond the duodenum has negligible effects on overall nutrient absorption.

Question 3

Warfarin and Vit K
Formation of Vit K dependent blood clotting factors in the liver (Factors II, VII, IX, X) is inhibited by warfarin resulting in an anticoagulation effect. Significant Vit K intake from an EN formulation can antagonize this anticoagulation effect and result in treatment failure.

Answer 3

Warfarin and Vit K
Most EN formulations marketed today contains modest amts of Vit K and provides the daily Vit K intake similar to average dietary intake from foods (90 to 118mcg/d in adults).
Consistent intake of a EN formulation containing

Question 4

There have been evidence of warfarin resistance in EN pts with relatively low Vit K intake. How would we modify the EN schedule to treat the warfarin resistance? How do we know this modification work or how do we evaluate this effective of the modification?

Answer 4

1. Initiate a trial of holding the EN for at least 1hr before and after the warfarin dose.
2. Checking the prothrombin time (PT) and the International Normalized Ratio (INR) within a few days after modification of EN. Increases in PT and INR should show the effectiveness in correcting the warfarin resistance. Another route in treating the warfarin resistance is using alternate anticoagulant therapy like low-molecular wt heparin.

Question 5

Phenytoin (Dilantin) and EN

What are the two methods used to prevent drug-nutrient interaction or ineffectiveness of the Dilantin?

Answer 5

1. Holding EN formulation at least 1hr and preferably 2hr after and before dilantin administration.
2. Some practitioners elect to continue adjusting the dilantin dose to achieve serum conc bcuz adjusting the EN can create problems related to inadequate EN delivery. High Dilantin doses are required with this method and monitoring dilantin serum levels is recommended.

Question 6

Carbamazepine - binding of carbamazepine to a component of EN formulations has not been demonstrated; thus, it is unclear if holding administration of the EN formulation for 2hrs before or after the drug dose, as has been recommended, is the best method of mitigating this potential interaction. Because an EN-carbamazepine interaction seems most probable with postpyloric administration, it would reasonable to hold feedings ac/pc drug administration in this population

Answer 6

Gastric administration cld be cautiously monitored w/out routinely holding feeding unless there’s evidence of an interaction.
Carbamazepine suspension shld be diluted at least 1:1 w/ water if administration via a feeding tube because drug loss in the feeding tube seems to be reduced w/ dilution.

Question 7

Fluoroquinolones - significant decreased in bioavailability when administered with EN formulation have been recorded in healthy volunteers and hospitalized pts. Therefore current recommendation is to hold administration of EN formulation for at least 1hr before a fluoroquinolone dose and 2hrs after the dose.

Answer 7

Warfarin - its resistance due to protein binding has not been adequately studied to confirm this as a mechanism of DNI. Use of a free a.a (elemental) EN formulation is expected to prevent the interaction. Alternate methods includes increasing warfarin dose or change to an alternate anticoagulant therapy.