Ch 18: Drug-Nutrient Interactions Flashcards
An alert and oriented adult pt is receiving continuous infusion of a standard, fiber-containing EN formulation through an 8-Fr NG tube. Drugs administered by bolus through the side port of the tube are: phenytoin suspension (400mg/d), nizatidine (150mg Q12H). The feeding tube becomes occluded and must be removed. A new tube is placed because a long-term tube will not be considered until after a swallow study is completed 2.5 weeks from now. Which of the following measures is most appropriate for preventing occlusion of the new tube?
A. Replace the 8-Fr with an 18-Fr NGT
B. Flush the feeding tube with 15 ml water before/after administering each med
C. D/c the fiber-containing formulation and initiate feeds with a fiber-free formla
D. Hold the feeding infusion x2 hours before/after administering phenytoin
B. Flush the feeding tube with 15 ml water before/after administering each med
Likely cause is improper flushing technique. Flush with a min of 15 mL of water before/after each med; 30 mL is commonly recommended and may be required to properly flush longer or larger tubes
A = uncomfortable in awake pt; C = min effect; D = enhance drug abs
The EN formulation for a home pt w/ PEG tube changes from: 1 kcal/mL (high protein/fiber-containing)
To: 1.5 kcal/mL (low CHO, 55% fat, 15% less protein/d, no fiber)
What component of the new formulation is most likely to contribute to interactions resulting from slow gastric emptying?
A. Lower fiber content
B. Lower protein content
C. Higher fat content
D. Higher energy density
C. Higher fat content
Pro/energy density slows, but to a lesser degree. Fiber: colonic xport
Which of the following is the preferred method of administering a hospitalized patient’s antihypertensive med when TF is started 2/2 poor PO intake?
A. By oral route
B. Oral liquid via feeding tube
C. Crushed tablet via feeding tube
D. IV route
A. By oral route
A medication ordered as liquid to be administered via feeding tube is availabe as IV form, capsule (powdered drug in hard gelatin capsule), and film-coated tablet. What is the most appropriate and cost-effective coice for administration of this med?
A. IV form via IV route
B. IV form via feeding tube
C. Make a slurry of the capsule’s powder and administer via feeding tube
D. Crush the tablet to a fine powder and administer via feeding tube
C. Make a slurry of the capsule’s powder and administer via feeding tube
What are physical interactions, and where do they occur?
Interactions that result in altered physical characteristics of the nutrition formulation or the drug
Occur in delivery device before drug/nutrients reach the patient
Table 18-1
What is the most frequent physical interaction?
Occlusion of the feeding access device
What is a side effect of physical interactions?
Reduced bioavailability of drug or nutrients
Variables to consider when assessing risk of physical interactions
- pH: what pH is the drug and EN/PN is most stable at?
- Presence of anions and cations known to react chemically
- Concentration and chemical complexity of nutrients
- Time, temperature, duration of exposure
Signs of incompatability in PN
- Visual changes: turbidity, haziness, cloudiness, color changes, precipitate formation
- Emulsion disruption in lipid-containing PN
What happens when Octreotide acetate is added to PN?
**No visual changes
Develops glycosyl octreotide conjugate and loss of drug activity
MVIs are prepared to be compatible with PN formulations. Certain vitamins have limited stability - why?
Give an example of one vitamin
Lose activity d/t hydrolysis, photo-degeneration, other forms of chemical degradation
Thiamin
What affects physical and chemical stability?
pH
Are PN solutions are acidic or alkaline?
slightly acidic (5-6.5)
Drugs requiring high pH or low pH for best solubility are usually ____ with PN
incompatible
What does increasing time or exposure between PN and drug do?
Ex: admixture of drug + PN vs co-infusion
increases risk for interactions
Additional components in PN that can influence compatibility and stability:
- Additional components in PN that can influence compatibility and stability:
- Dextrose and AA concentration
- Specific brand of AA used for compounding
- Inclusion of ILE and specific type of ILE
- Electrolyte concentrations and specific electrolytes added
- Addition of trace elements, heparin, insulin, etc
What antibiotic class is compatible with PN?
cephalosporin class
(including ceftazidime)
What antifungal medication is compatible with PN?
Fluconazole
Is foscarnet (antiviral) compatible for co-infusion with PN?
- Limited evidence suggests foscarnet (antiviral) is compatible for co-infusion with PN
- Other data suggests incompatibility is with calcium-containing solutions
Using enteral feeding tubes as drug delivery device increases the risk for:
interactions between the drug, feeding tube, and formula
What seems to be a critical property for determining the risk of developing a physical interaction
Presence of complex protein
Intact or whole protein – not hydrolyzed protein or free AA
Protein sources that have some effect on interactions:
- Whey
- Casein
- Soy
Does the fiber content, nitrogen content, and dilution of EN affect the risk of physical interactions with drugs?
No
Drugs in liquid forms:
And what two forms are important to know?
May more important than the actual drug as these two components are selected to optimize solubility of a particular drug
- Acidic pH
- Base components – sugar-water syrups, alcohol-containing elixirs, oil-based products
Drugs in liquid forms + EN
Can demonstrate undesirable effects (precipitation, curdling, clumping)
What 3 drugs were incompatible with hydrolyzed protein EN formulations?
- Potassium chloride liquid
- MCT oil
- Methenamine suspension (antibiotic, eliminates bacteria that causes UTIs)
What liquid drug was considered incompatible with fiber and compatible without fiber in EN formulas?
Reglan syrup
contained soy polysaccharide as fiber source
Best route of drug administration:
Oral route
When this is actually possible
What fluid is used to flush VADs?
- Sodium chloride 0.9% is usual fluid to flush VADs
- Sometimes required 5% dextrose solution
Is use of thrombolytic agents an effective way to clear drug precipitate in VADs?
NO
Altering pH within VAD lumen to make the drug more soluble can often clear occlusions
What are viable options when you can’t change an EN formula, remove ILE from PN, etc?
- Alternative dosage forms (powder from capsule → slurry vs use of elixir)
- Therapeutic drug equivalent that has different potential to interact
What is a drug dosage form?
The drug + nonmedical components (excipients) needed to make a stable and effective product
(ex: palatable for PO administration, non-irritating for dermal administration)
Examples of drug dosage forms:
- Enteric coated tablets – protect drugs from gastric acid
- Long acting products – reduce # daily doses
- Sublingual or rectal – avoid first-pass metabolism in liver
What is the most common method of altering dosage form?
Crush or dissolve solid dosage forms → create liquid for administration via feeding tube
What sort of drugs/nutrients can be absorbed by plastics?
High fat solubility: more likely to undergo absorption with plastics
Insulin can also be absorbed
Loss of drugs to feeding tubes:
- Warfarin + polyurethane feeding tube material
- Phenytoin/carbamazepine suspension losses – adherence to intraluminal surface of tube
Solution to avoid drug loss and potential physical DNI between drug and feeding tube?
Make slurries, dilute, flush the tube well after med administration
Dosage forms - PERT?
- Pancreatic enzymes – no viable options
- Needs enteric coating to be dissolved in sodium bicarbonate solution → crush → then administer with small volume of sodium bicarb
What are common additives to liquid forms that can cause an osmotic effect?
Mannitol, sucrose, sorbitol
What effect does water have on chemical reactions?
Water tends to accelerate chemical reactions → loss of drug activity
What are typical chemical reactions → stability issues?
Photodegradation, oxidation, hydrolysis
What nutrients/drugs bind to tubing and thus result in a loss?
What can be done to help decrease losses?
- High fat solubility: more likely to undergo absorption with plastics
- Insulin can also be absorbed
- Vitamin A lost → DEHP-containing plastics
- Warfarin + polyurethane feeding tube material
- Phenytoin/carbamazepine suspension losses – adherence to intraluminal surface of tube
Make slurries, dilute, flush well
Postpyloric administration like will cause reduced bioavailability in the following drugs:
- Carbamazepine
- Itraconazole
- Tetracycline
Bioavailability of these drugs depends on stability in acid environment:
- Carbamazepine – acid-stable drug
- Digoxin – hydrolyzed in presence of acid
Impact of slow gastric emptying on certain drugs:
Dissolution of soluble (tetracycline) and poorly soluble (carbamazepine, digoxin) is improved
What inhibits CYP450 enzyme → increased serum level of drugs?
Grapefruit juice
What macro/micronutrients impact drug metabolism through effects on enzymes of mixed-function oxidase system in liver?
- High protein intake
- Riboflavin
- Niacin
- Large ascorbic acid doses
Most data is from animal studies
What happens when macro/micronutrients impact drug metabolism through effects on enzymes of mixed-function oxidase system in liver?
Results in increased clearance of drugs metabolized by these enzymes
Most data is from animal studies
How can protein intake influence blood flow?
Low intake → reduced blood flow to kidney → reduced renal elimination
Most data is from animal studies
Which divalent and trivalent minerals known to form complexes with certain drugs and → poor absorption of drugs?
- calcium, magnesium, iron
- tetracycline and ciprofloxacin
Oxalate from ascorbic acid degradation + PN interaction
interacts with calcium in PN formulations → insoluble precipitate
How can disease affect pharmacokinetic parameters?
- Albumin – binds many drugs (phenytoin, valproic acid, warfarin)
- Edema, increased body water, and decreased muscle mass
- Alterations in organ function and perfusion
- Effects on GI motility
Phenytoin + DNI
Theory is that mechanism of interaction is related to pH and phenytoin binding to either tubing or an EN component (e.g., protein)
Hold EN x1-2 hours before/after drug administration appears to be successful
* May minimize the negative impact on oral drug bioavailability
Carbamazepine + DNI
- Insoluble drug and is acid stable – slow gastric emptying improves bioavailability
- Post-pyloric administration may result in poor bioavailability
- Adequate dilution of suspension (or slurry from crushed tablet)
Fluoroquinolones + DNI
Bioavailability of some abx seems to be reduced in EN formulations
* Reduced bioavailability reported with repeated doses of ciprofloxacin via NGT in critically ill patients receiving continuous feeds
* Significant absorption in duodenum
* Jejunal feeds have high impact on bioavailability
Should you hold feeds when administering Fluoroquinolones?
Many facilities hold EN x1 hours before and x2 hours after drug administration
* Data for holding EN is very limited
* Holding feeds remains a potential method for mitigating EN interactions with ciprofloxacin and norfloxacin
Holding feeds for other fluoroquinolones should not be done routinely
Warfarin + DNIs
Proposed mechanism for warfarin resistance with low Vit K intake: binding of warfarin to component in EN formula – most likely protein
- Many questions to theory of warfarin-EN protein binding
Loss of warfarin noted when infused through which type of feeding tube?
polyurethane feeding tube
Why is assessing drug interactions with Warfarin prior to changing TF regimen important?
- Paroxetine (SSRI) increases INR
- Nafcillin decreases INR - could contribute to warfarin resistance
- Acetaminophen increases INR significantly in some patients
Potential methods to mitigate Warfarin-EN interactions:
- Concentrated form of drug in slurry + rapid administration → minimize contact with feeding tube
- Separating drug administration from EN infusion
- Increasing Warfarin dose until therapeutic PT/INR is achieved
- Changing to alternative coagulation therapy that does not react with EN
