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Master Deck > Drug-Nutrient Interactions > Flashcards

Drug-Nutrient Interactions Flashcards

1
Q

Define DNI.

A

Drug Nutrient Interaction ASPEN defines DNI as “an event that occurs when nutrient availability is altered by a medication, or when a drug effect is altered or an adverse reaction is caused by the intake of nutrients.’

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2
Q

The presence of XXXX seems to be a critical property for determining risk of developing a physical interaction.

A

Complex protein (ie: intact or whole protein)

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3
Q

XXXX, XXXX, and XXXX of the EN formulation have not been shown to affect the risk of physical interactions with drugs in studies reported in the literature.

A

Fiber content N content Dilution of the EN formulation

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4
Q

What two factors are of particular importance with drugs in liquid form?

A
  1. Acidic pH 2. Base components, especially sugar-water syrups, alcohol-containing elixirs, or oil-based products.
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5
Q

(TRUE/FALSE) 1/3 of drugs in liquid dosage have demonstrated undesirable effects with at least 1 EN formulation.

A

TRUE.

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6
Q

(TRUE/FALSE) Physical interactions are best avoided by not allowing drugs to mix with either PN or EN formulations. Ideally, drugs should be administered via a route other than the feeding administration device.

A

TRUE.

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7
Q

When a drug must be administered through the same device as the PN or EN formulation, what is the procedure?

A

The feeding should be stopped, and the access device should be flushed with fluid that is compatible with the PN or EN formulation as well as the drug. The access device should be flushed before and after drug administration and between drugs if multiple drugs are administered.

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8
Q

What is the ideal fluid of choice for flushing VADs?

A

0.9% sodium chloride, or sometimes 5% dextrose solution is required

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9
Q

What is the ideal fluid of choice for flushing EN tubes?

A

Water

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10
Q

(TRUE/FALSE) Acidic products, such as carbonated beverages and cranberry juice may be used for flushing.

A

FALSE. They can be particularly problematic.

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11
Q

(TRUE/FALSE) The minimum recommended volume used to flush enteral feeding tubes in adults is 30 mL.

A

FALSE. 15 mL; although usually larger volumes are often used.

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12
Q

What type of medications (as a general rule), should not be crushed or dissolved?

A

Special dosage forms such as long-acting, sustained-release, slow-release, or delayed-release containing several doses in 1 tablet/capsule Watch for: CD, CR, ER, LA, SA, SR, TR, XL, or XR (generally these need to be taken intact)

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13
Q

(TRUE/FALSE) Administration into the jejunum negates the need for an enteric coating since the jejunum is where the coating is designed to dissolve.

A

TRUE. Dissolving the coating in bicarbonate solution, then crushing the table is acceptable for jejunal administration, although the process can be slow (30 to 45 minutes) and caution is still required to avoid tube occlusion.

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14
Q

(TRUE/FALSE) Film coatings are used to make tablets easier to swallow or to mask unpleasant taste. They also impart special characteristics such as those associated with enteric coatings.

A

FALSE They DO NOT impact special characteristics. Crushed film-coated tables should not result in altered drug activity or increased risk of adverse effects. They can be problematic because they often remain as undissolved pieces that become sticky in water and can occlude the feeding tube.

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15
Q

(TRUE/FALSE) Intact pellets may be administered through the feeding tube, provided the pellets are small enough to completely pass through the tube.

A

TRUE. Usually a larger tube (min. 16-Fr) is necessary for successful administration of these dosage forms.

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16
Q

What liquid would you use to administer a drug with intact pellets?

A

Acidic juice as the vehicle for microencapsulated pieces as it should reduce the risk of the beads or pellets sticking to the tube. NOTE: Water should be used to clear the tube of the EN formulation before and after administration of the acidic-juice mixture to avoid physical DNIs between the EN formulation and an acidic product.

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17
Q

What is the recommendation administration for pancreatic enzmyes?

A

With no viable options, it may be necessary to dissolve an enteric coating on the beads or pellets in a sodium bicarb. solution, then crush and administer the drug with a small volume of sodium bicarbonate solution.

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18
Q

(TRUE/FALSE) Diluting hyperosmolar products with water before administration reduces the osmolality and may reduce the risk of GI intolerance.

A

TRUE.

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19
Q

(TRUE/FALSE) Proper tube flushing cannot prevent pharmaceutical interactions. However, flushing with adequate quantities of water remains an important technique to prevent concomitant physical interactions

A

TRUE. Pharmaceutical interactions may also be minimized by using alternate routes of administration or by using a therapeutic alternative that is available in a form conductive to administration via the feeding tube.

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20
Q

Define pharmacokinetics.

A

Refers to studies of the time course for drug absorption, distribution, metabolism, and excretion. The term can also be applied to nutrients because the same processes occur with nutrients.

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21
Q

Define bioavailability.

A

Describes the amount of drug that reaches systemic circulation after administration.

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22
Q

List some examples of what can decrease bioavailability.

A
  • Drug or nutrient loss during administration
  • Adverse pH effects
  • Complex formation between nutrient(s) and drug
  • Presystemic metabolism in the gut mucosa (CYP450)
  • Hepatic first-pass metabolism
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23
Q

(TRUE/FALSE)

The potential for chemical reactions and stability issues exists whenever a solid dosage form of drug is made into a liquid form.

A

TRUE.

Water tends to accelerate chemical reactions that result in loss of drug activity.

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24
Q

Rapid gastric emptying accompanied by rapid GI transit can result in XXX absorption because…..

A

Poor absorption because there is insufficient contact time between the drug/nutrient and the absorptive surface of the small bowel.

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25
Q

(TRUE/FALSE)

Delivery of the EN formulation and drugs into the small bowel bypasses problems with gastric emptying.

A

TRUE.

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26
Q

Where does presystemic metabolism occur?

A

Gut mucosa and liver

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27
Q

Define CYP450 enzyme system.

A
  • Includes many isoenzymes involved in drug metabolism and is a major component of presystemic metabolism.
  • ~60% of drugs currently available are metabolized by these isoenzymes, specifically CYP3A4
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28
Q

What is a classic example of CYP450-mediated DNI?

A

Drug interactions with grapefruit juice

Grapefruit juice inhibits the isoenzyme CYP34A, thereby increasing serum levels of drugs normally metabolized by this isoenzyme.

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29
Q

What is P-glycoprotein?

A
  • The best-known transporter
  • Serves as an efflux mechanism to pump xenobiotics (drugs and other chemicals/substances not normally present in the body), out of the cells and prevent entry to the compartment that the cells protect.
  • Located on the luminal surface of cells lining the small bowel and prevents systemic absorption of certain drugs.
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30
Q

(TRUE/FALSE)

The alterations in body composition associated with malnutrition, edema, increased body water and decreased lean muscle may affect pharmacokinetics parameters.

A

TRUE.

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31
Q

What is phenytoin prescribed for?

What methods are used to manage DNIs with EN and this medication?

A

Anti-epileptic drug, also used as an anticonvulsant

None of the methods used are completely reliable, and monitoring of serum phenytoin concentrations is highly recommended and consistency of administeration is important

  • Holding administration of the EN for at least 1 hour, and possibly 2 hours, before and after phenytoin administration, seems to produce the most consistent results
  • Dilution of phenytoin suspension is also recommended when the suspension is administered through a feeding tube
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32
Q

What is carbamazepine used for?

What are the methods used for controlling DNIs with EN and this drug?

A

Anticonvulsant

The first choice of methods is:

  • Adequate dilution of the suspension (or slurry from a crushed tablet) prior to administration and adequate flusing after the dose
  • Dilution should be at least 1:1, preferably 3:1, with water if administered via a feeding tube because drug loss in the feeding tube seems to be reduced with dilution.

When that fails (in postpyloric administration):

  • It would be reasonable to hold feedings before and after drug administration in this population.
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33
Q

What method is recommended for preventing DNIs with fluoroquinolone antibiotics?

A

Holding feedings remains a potential method for mitigating EN interactions with ciprofloxacin or nofloxacin; however, holding feedings with other fluoroquinolones should not be done routinely.

NOTE: Many facilities follow a policy of holding EN for at least 1 hour before a fluoroquinolone dose and 2 hours after each dose, as recommended previously. This approach does seem to minimize the effects; however the data is very limited especially in TF patients.

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34
Q

What methods are used for mitigating DNIs with warfarin with low vitamin K intake?

A
  • No definitive recommendations can be provided associated with relatively low vitamin K intake.
  • Response to warfarin therapy must be closely monitored with EN therapy is started, stopped, or altered
  • Holding EN around administration of warfarin through a feeding tube should NOT effect bioavailability, and they did NOT recommend holding feedings to mitigate warfarin-EN interactions
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35
Q

(TRUE/FALSE)

One proprosed mechanism for warfarin resistance with low vitamin K intake is binding of warfarin to a component of the EN formulation, most likely protein.

A

TRUE.

Use of a free AA (elemental) TF is expected to prevent this interaction; however, that is not recommended.

Practitioners may elect to manage the interaction by other methods (increase dose or use another therapy)

36
Q

What are potential methods of mitigating the warfarin-EN interaction?

A
  • Rapidly administering a concentrated form of the drug to minimize contact with the feeding tube
  • Separating warfarin administration from EN admin (holding EN for at least 1 hour before and after, is second approach)
  • Increasing the warfarin dose until a therapeutic PT/INR is achieved, OR
  • Changing to an alternative anticoagulation therapy that does not interact with EN therapy.

*Minimizeing contact with the feeding tube has a low potential to cause unintended consequences and is a reasonable first approach.

37
Q

What are the factors related to nutrition support that may influence drug-nutrient interactions?

A

The type and site of access
Method of administration
Content of the PN or EN formulation

38
Q

How is a drug-nutrient interaction defined?

A

An event that occurs when a nutrient availability is altered by a medication, or when a drug effect is altered or an adverse reaction is caused by the intake of nutrients

39
Q

What are the types of physical drug-nutrient interactions?

A

Precipitation in PN or EN formulations
Disruption of emulsion for ILEs or EN formulation
Altered viscosity, change in consistency, clumping, or curdling of EN formulation

40
Q

What are the variables to consider when assessing the risk of a physical drug-nutrient interaction?

A

The pH at which the drug and PN/EN formulation is most stable
Presence of cations and anions known to react chemically
Concentration and chemical complexity of nutrients
Time, temperature, and duration of exposure to one another

41
Q

What is a frequent outcome of physical drug-nutrient interactions?

A

Occlusion of the feeding access device

42
Q

What are visually evident physical changes in PN formulations that indicate incompatibility?

A

Turbidity
Haziness
Cloudiness
Color changes
Precipitate formation
Emulsion disruption in lipid-containing PN

43
Q

List some drug-nutrient physical interactions that result in a loss of drug or nutrient activity that requires chemical or molecular analysis for detection in which no visible changes occur in the product

A

Admixture of octreotide acetate to PN creates incompatibility due to development of a glycosyl octreotide conjugate and loss of drug activity.
Injectable multivitamins are compatible with PN formulation, but some vitamins (thiamin) have limited stability and begin to very quickly lose their activity once added to the PN formulation because of hydrolysis, photodegradation, or other forms of chemical degradation

44
Q

What factor(s) is most likely to result in occlusion of the vascular access device when a patient is receiving several drugs and PN through the VAD?
Scenario: Patient s/p hematopoietic cell transplant receiving PN with separate ILE and patient-controlled analgesia with morphine sulfate through his tunneled VAD. Ceftazidime, Fluconazole, and Foscarnet are administered through the VAD. Pt with increased calcium demand so calcium chloride 1gm q 8 hrs is ordered for adding to PN (due to shortage of calcium gluconate and bc patient requires high phosphate content in PN which would limit addition of calcium gluconate). Meds ordered for “minimum fluid”. VAD is double lumen, one lumen is occluded. Morphine is continued through the line; Foscarnet, Ceftazidime, Fluconazole, and PN are on hold until access can be obtained.

Patient was receiving a blood transfusion when the calcium dose was due, and was to receive platelets once the red cell transfusion was complete. Pt’s nurse co-infused calcium chloride with the PN, which contained above-standard amounts of potassium phosphate due to effects of Foscarnet. A 0.22-micron filter was on the PN lumen of a bifurcation device connected to the catheter lumen; however, there was no filter after the calcium mixed with the PN solution

A

Review administration regimen for physical interactions that occlude the VAD
Composition of PN and co-infused drug should be reviewed

Antibiotic Ceftazidine and Fluconazole are compatible for co-infusion with PN. Foscarnet can be incompatible with calcium-containing solutions and may cause problems if co-infused with PN containing calcium. High likelihood of calcium precipitating with phosphate when calcium chloride is co-infused with PN.

Altering the pH for this occlusion within the VAD to make the drug more soluble will likely clear the occlusion. Consider risk vs benefit of line salvage first. Confirm compatibility between catheter materials and recommended clearance solution.

With calcium-phosphate precipitate, decreasing the pH by instilling 0.1-N hydrochloric acid will increase calcium phosphate solubility and may be effective in clearing the occlusion.

45
Q

The presence of what specific nutrient component in EN formula seems to be a critical property for determining risk of developing a physical interaction?

A

Complex protein (intact or whole protein) (caseinates, soy, whey)

46
Q

Why is EN formula dilution not recommended?

A

Increases the risk of microbial contamination

47
Q

What two factors are of particular importance with drugs in liquid form in regard to their potential to cause drug-nutrient interaction?

A

Acidic pH and base components, especially sugar-water syrups, alcohol-containing elixirs, or oil-based products

48
Q

Why is the risk of undesirable interactions between drugs and EN formulations containing soluble fibers greater than with soy polysaccharide?

A

Soluble fibers have a propensity to form gels.

49
Q

How are physical drug-nutrient interactions best avoided?

A

By not allowing drugs to mix with either EN or PN formulations. Ideally drugs would be administered via a route other than the feeding administration device (VAD or feeding tube)

50
Q

What are the other available routes for medication administration other than the VAD or feeding tube?

A

Oral, rectal, transdermal, sublingual, intramuscular, subcutaneous

51
Q

What is the most effective method for preventing feeding tube occlusion related to medication administration in a patient receiving jejunal feedings to supplement inadequate oral intake associated with gastroparesis?
Scenario: patient w/ gastroparesis 2/2 T2DM. Thin liquids empty from the stomach with only slight delay; progression of thick liquids and solids into the duodenum is severely delayed. GJ tube is placed and patient is started on TF + thin liquid diet.

A

If patient is able to eat by mouth, medications should be given via the oral route as these do not cause tube occlusion. Medications taken with water should have minimal effect on gastric emptying compared with water alone, and thin liquids empty with only slight delay per the GI evaluation

52
Q

What is the usual fluid of choice for flushing VADs?

A

Sodium chloride 0.9%, but sometimes 5% dextrose is required

53
Q

What is the fluid of choice for flushing enteral feeding tubes?

A

Water

54
Q

What is the minimum recommended volume used to flush enteral feeding tubes in adults?

A

15 ml

55
Q

What should be done if a drug must be administered through the same device as the PN or EN formulation?

A

Feeding should be stopped, and the access device should be flushed before and after drug administration and between drugs if multiple drugs are administered

56
Q

What are other potential methods of preventing physical interactions with PN and EN formulations?

A

Altering the infusion time (cyclic regimen), altering the nutrition formulation (changing to hydrolyzed or free amino acid EN formula), or altering the drug

57
Q

Interactions that occur because a drug dosage form is altered are more likely to occur with EN or PN therapy?

A

EN therapy

58
Q

What are some alternate dosage forms that drugs are available in?

A

Enteric coated (to protect the drug from gastric acid, or to protect the stomach from an irritating drug)
Long acting (to reduce the number of daily doses)
Sublingual or rectal (to bypass first-pass metabolism in the liver)

59
Q

What can happen if you alter certain drug dosage forms?

A

Can dramatically increase or decrease drug bioavailability and trigger adverse effects or, conversely, destroy the active ingredient

60
Q

What is the most common method of altering a dosage form?

A

Crushing or dissolving solid dosage forms to create a liquid for administration via the feeding tube

61
Q

How should solid dosage forms that are appropriate to crush/alter be prepared for administration in the feeding tube?

A

Prepared as a very fine powder and mixed with warm water before administration. Many capsules may be opened and the contents administered after forming a slurry with water from the powder or finely crushed solids

62
Q

Why should special dosage forms such as long-acting, sustained-release, slow-release, or delayed-release not be crushed or dissolved?

A

They contain several doses in 1 tablet and are designed to slowly release in the GI tract, often over 12-24 hours. Crushing may cause immediate release of the total drug dose, increasing the risk of toxicity and reducing efficacy

63
Q

Abbreviations to be aware of in a drug that indicates they need to be taken intact and should not be crushed or dissolved for administration:

A

CD, CR, ER, LA, SA, SR, TR, XL, XR

64
Q

Why should enteric coated (denoted as EC after the drug name) drugs generally not be altered for administration

A

The coating is intended to protect a drug from destruction by gastric acid or to protect the stomach from irritation caused by the drug.

65
Q

What should be done for administration of enteric coated drugs into the jejunum?

A

Administration into the jejunum negates the need for an enteric coating since the jejunum is where the coating is designed to dissolve. Can dissolve the coating in bicarbonate solution, then crush the tablet. Can be a slow process (30-45 minutes) and caution is still required to avoid tube occlusion

66
Q

What are film coatings on medications?

A

Used to make tablets easier to swallow or to mask unpleasant taste, but they do not impart special characteristics such as those associated with enteric coating. Often remain as undissolved pieces in water and can occlude the feeding tube

67
Q

Which of the available dosage forms of Lansoprazole should be ordered, and how should it be administered through a nasal-jejunal feeding tube?
Scenario: Pt receiving Lansoprazole (Prevacid) d/t GI bleed. Being fed via small-bore nasal-jejunal tube d/t poor nutrition status, inability to take oral diet, and aspiration risk while on mechanical ventilation. Extubated and IV lansoprazole stopped

A

Discuss options for acid suppression and address whether acid suppression needs to be continued once off mechanical ventilation and out of ICU. If acid suppression is to continue, the histamine-2 receptor antagonist on the hospital’s formulary may be adequate. Lansoprazole is problematic for administration through small-bore feeding tube. Either an extemporaneously prepared oral suspension or therapeutic alternative should be considered to avoid occlusion of the feeding tube.

68
Q

Why is Lansoprazole problematic for administration through small-bore feeding tube using commercially available dosage forms?

A

Available as a delated-release capsule and as a delayed-release ODT. These dosage forms should not be crushed because of the delayed release characteristic. Capsule can be opened and intact granules administered with apple juice (40ml) via feeding tube, however the small-bore tube is not of adequate size.

69
Q

What is the adequate feeding tube size for administration of intact granules from the capsule form of a medication?

A

16 Fr

70
Q

Why should IV dosage forms not be administered via GI tract?

A

They are poorly suited to withstand gastric acidity and enzyme activity within the GI tract. Substantial drug loss can occur. IV electrolyte preparations are an exception.

71
Q

What is a potential side effect of using oral liquid dosage forms of certain medications?

A

Can have high osmolality and result in diarrhea or cramping. Osmolality of oral liquids and IV drugs often exceeds 1000 mOsm/kg.

72
Q

What can help reduce the risk of GI intolerance with hyperosmolar products?

A

Diluting with water before administration reduces the osmolality

73
Q

What sweetening agents often used in oral liquid dosage forms contribute to increased osmolality?

A

Mannitol, sucrose, and sorbitol

74
Q

Why is sorbitol a particularly troublesome sweetening agent when added to oral liquid dosage forms?

A

The cumulative daily dose of sorbitol from oral liquid drugs can reach 20-50 gm, which is an amount commonly used as an osmotic laxative. Sorbitol doses of only 5-10 mg daily cause a considerable portion of people to experience bloating and flatulence

75
Q

Why do pharmacokinetic drug-nutrient interactions occur?

A

Can occur as the result of multiple factors: administration of EN or PN, the drug, the PN or EN formulation, the disease process (especially if it affects protein status, organ perfusion, and GI motility)

76
Q

What is bioavailability?

A

The amount of drug that reaches systemic circulation after administration

77
Q

What factors can cause product loss that decrease bioavailability?

A

Drug or nutrient loss during administration, adverse pH effects, complex formation between nutrients and drug, presystemic metabolism in the gut mucosa, and hepatic first pass metabolism

78
Q

What are 2 examples of drugs with a “local” effect?

A

Antacids and sucralfate. They have no therapeutic effect with postpyloric delivery because they act locally in the stomach

79
Q

Slow gastric emptying increases the extent of absorption for which nutrients?

A

Those that benefit from acid exposure (iron, calcium, magnesium) and those that undergo active absorption by a saturable mechanism in the upper small bowel (riboflavin)

80
Q

The effect of delivery into the small bowel on drugs largely depends on what?

A

The drugs’ solubility and need for acid exposure for absorption

81
Q

Clinical experience suggests that holding EN administration how frequently for drug administration is likely to result in inadequate nutrition support and deterioration of nutrition status unless a volume-based feeding protocol is used?

A

Holding EN administration for approximately 1-2 hours every 6-8 hours

82
Q

For PN formulations, what are drug-related pharmacokinetic DNI factors largely associated with?

A

Stability of the IV dosage form and the potential for loss of drug activity due to chemical reactions (photodegradation, oxidation, hydrolysis)

83
Q

What is presystemic metabolism?

A

Metabolism that occurs before reaching systemic circulation, occurs in both the gut mucosa and liver

84
Q

Estimated that what % of drugs currently available are metabolized by CP450 isoenzymes and which interaction is a classic example of this?

A

60% of drugs. Grapefruit juice inhibits the isoenzyme CYP3A4, thereby increasing serum levels of drugs normally metabolized by this isoenzyme

85
Q

Consistent intake of an EN formulation containing __ mcg of vitamin K per 1000 kcal is not expected to cause warfarin resistance

A

<100 mcg of vitamin K per 1000 kcal

86
Q

What administration regimen of Phenytoin with EN produces the most consistent results?

A

Holding EN for at least 1 hour and possibly 2 hours before and after phenytoin administration

87
Q
A

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