Food-Drug Interactions

Food-Drug Interactions

• Dr/ Noha Abbas Telep

• Associate professor of clinical pharmacology
faculty of medicine zagazig university
 Drug-nutrient interaction

• The result of the action between a drug and a nutrient

that would not happen with the nutrient or the drug alone
 Food-drug interaction

• A broad term that includes drug-nutrient interactions and the effect of a

medication on nutritional status

• For example, a drug that causes chronic nausea or mouth pain may result

in poor intake and weight loss

Benefits of Minimizing Food Drug
Interactions
• Medications achieve their intended effects
• Improved compliance with medications
• Less need for additional medication or higher dosages
• Fewer caloric or nutrient supplements are required
• Adverse side effects are avoided
Benefits of Minimizing Food Drug
Interactions

• Optimal nutritional status is preserved

• Disease complications are minimized

• The cost of health care services is reduced

Patients at Risk for Food- Drug
Interactions
• Patient with chronic disease
• Elderly
• Fetus
• Infant
• Pregnant woman
• Malnourished patient
• Allergies or intolerances
 Key Terms
• Bioavailability: degree to which a drug or other substance reaches the
circulation and becomes available to the target organ or tissue.

• Half-life: amount of time it takes for the blood concentration of a drug

to decrease by one half of its steady state level.

• Side effect: adverse effect/reaction or any undesirable effect of a drug.

 Pharmacokinetics
Movement of drugs through the body by

• Absorption

• Distribution

• Metabolism

• Excretion
 Pharmacodynamics

• The mechanism of action, e.g. how a drug works Often the drug

molecule binds to a receptor, enzyme, or ion channel, producing a

physiological response

• Actions of the drug and unwanted effects

 Pharmacogenomics

• Genetically determined variations that are revealed solely by the

effects of drugs
• Affect only a subset of people
• Examples include G6PD (glucose-6-phosphate dehydrogenase)
enzyme deficiency, warfarin resistance, and slow inactivation of
isoniazid (IHN).
Effect of Food on Drug
Therapy
 Absorption
• Presence of food and nutrients in intestinal tract may affect absorption of drug
e.g. thyroid drugs
• Antiosteoporosis drugs bisphosphonate drugs Fosamax or Actonel: absorption
negligible if given with food; ↓ 60% with coffee or orange juice.(at least taken
30 minutes before food)
• Absorption of iron from supplements ↓↓ 50% when taken with food (vit c
enhance iron absorbtion)
Absorption of iron
• Absorption of iron from supplements ↓↓ 50% when taken with food
• Best absorbed when taken with 8 oz of water on empty stomach
• Food may ↓↓ GI upset
• If take with food, avoid bran, eggs, fiber supplements, tea, coffee,
dairy products, calcium supplements
Effect of PH of the stomach
• GI pH can affect drug absorption
• Achlorhydria or hypochlorhydria can reduce absorption of
ketoconazole
• so if person treated from GERD Antacid medications can result in
reduced acidity in the stomach

• Taking these meds with orange or cranberry juice can reduce stomach
pH and increase absorption
Absorption may increased by food

• Presence of food enhances the absorption of some medications

• Bioavailability of cefuroxime Axetil (Ceftin), an antibiotic, is 52% after a meal
vs 37% in the fasting state
• Absorption of the antiretroviral drug saquinavir is increased twofold by food
How to avoid absorption interactions‫؟‬
• Stop unnecessary supplements during drug therapy or give drug 2 hours
before or 6 hours after the mineral
• Food speeds GI speed – reduced absorption
As the increase fat content of meal
Adsorption
• Adsorption: adhesion to a food or food component
• High fiber diet may decrease the absorption of tricyclic antidepressants such
as amitriptyline (Elavil)
• Digoxin (Lanoxin) should not be taken with high phytate foods such as wheat
bran or oatmeal
• Cholestyramine ( antihyperlipideamic bile acid Sequestrant) adsorb fat soluble
vitamins and folic acid
Distribution
• 1) ↓albumin(main blood protein) → ↑ bioavailability of drugs
and potentiate their effect:- phenytoin → toxicity- warfarin →
bleeding
• Especially drugs with high plasma
Protein bounding
N.B. patient with albumin levels below
3g/dl are at increased risk for adverse effects
• 2) Body composition:- obese or elderly → higher ratio of adipose

tissue- So, fat soluble drugs may accumulate in the body ↑ risk

of toxicity.
Metabolism – Interaction with food
• Food---1) Act as structural analogue and so Compete for metabolic
enzyme.

• 2) Alter enzyme Activity Mechanism.

• Theophylline: a high protein, low CHO diet can enhance clearance

of this drug
• Cytochrome P-450 in GI, liver Grapefruit juice will alter this enzyme
• Effects occur 24 hours after ingestion
Food affect drug metabolism

• Grapefruit/juice: inhibits the intestinal metabolism (cytochrome P-450 3A4

enzyme) of numerous drugs (calcium channel blockers, HMG CoA
inhibitors, anti-anxiety agents) enhancing their effects and increasing risk of
toxicity;

• N.B. Grapefruit/juice may interfere with the absorption of other drugs

• Effect persists for 72 hours so it is not helpful to separate the drug and

the grapefruit

• Many hospitals and health care centers have taken grapefruit products

off the menu entirely

Drugs known to interact with grapefruit
juice
• Anti-hypertensives (filodipine,
nifedipine, nimodipine, nicardipine,
isradipine)
• Immunosuppressants (cyclosporine,
tacrolimus)
• Antihistamines (astemizole)
• Protease inhibitors (saquinavir)
• Lipid-Lowering Drugs (atorvastatin,
lovastatin, simvastatin)
• Anti-anxiety, anti-depressants
(buspirone, diazepam, midazolam,
triazolam, zaleplon, carbamazepine,
clomipramine, trazodone
Excretion

• Urine acidity will change drug excretion

• Cranberry juice will alter pH and cause

higher dissolution. This occurs with

sulfonamides(little souluable in acidic urine)

• Lime juice is most acidic

Nutrient affect drug excretions
—Patients on low sodium diets will reabsorb more lithium along with
sodium; patients on high sodium diets will excrete more lithium and
need higher doses(co transported)

—Urinary pH: some diets, particularly extreme diets, may affect urinary
pH, which affects resorption of acidic and basic medications

N.B. Lithium is a drug used in bipolar depression

Effect of drugs on food and nutrients
drugs can affect the absorption of food:

• Ciprofloxacin and Tetracycline form insoluble complexes with calcium in dairy

products or fortified foods.
• also zinc, calcium, magnesium, zinc or iron supplements; aluminum in
antacids
• Standard advice is to take the minerals at least 2 to 6 hours apart from the
drug
• H2 receptor blockers in treatment of GERD may impair absorption of vitamin
B12 by reducing cleavage from its dietary sources.
Drugs affect food metabolism
• Methotrexate resembles folate in structure and competes with the
enzyme that converts folate to its active form. Use of methotrexate
can cause folate deficiency.
• Some anticonvulsants (phenytoin & phenobarbitone) alter the activity
of liver enzymes causing increased metabolism of folate, vitamin D,
and vitamin K.
Drug affect nutrient excretion
• Isoniazid, an antituberculosis medication, is similar in structure to
vitamin B6 and block the conversion of vitamin B6 to its active form
treatment with isoniazide is for 6 months, B6 supplements are
routinely given
• Diuretics remove excess fluid from the body Some diuretics may also
increase loss of potassium along with fluids

• Loop diuretics (furosemide, bumetanide) increase excretion of potassium,

magnesium, sodium, chloride, calcium
• Patients may need supplements with long term use, high dosages, poor diets

• Electrolytes should be monitored

• Thiazide diuretics (hydrochlorothiazide) increase the excretion

of potassium and magnesium, but reduce excretion of calcium

(by enhancing renal reabsorption of calcium)

• High doses plus calcium supplementation may result

in hypercalcemia
• Potassium-sparing diuretics (spironolactone) increase excretion

of sodium, chloride, calcium

• Potassium levels can rise to dangerous levels if

patient takes K+ supplements or has renal

insufficiency
• Corticosteroids (prednisone) decrease sodium excretion, resulting in

sodium and water retention; increase excretion of potassium and calcium.

• Low sodium, high potassium diet is recommended

• Calcium and vitamin D supplements are recommended with

long term steroid use (lupus, RA) to prevent osteoporosis

Pharmacodynamic

• Modification of the drug action by food and nutrients

Food/Nutrient Effects on Drug Action
• 1)Alcohol with sedatives and other CNS depressants may produce
excessive drowsiness, incoordination and other signs of CNS
depression.
• 2)Alcohol is a stomach mucosal irritant so if combined with
NSAIDs may increase the risk of GIT ulceration and bleeding
• 3)Alcohol with Acetaminophen (don’t mix).
“Two or more alcoholic drinks per day can increase the liver toxicity of
acetaminophen. “This toxicity can happen even if a patient takes less than
the maximum 4 grams, or eight tablets, of acetaminophen per day.”

• This interaction can be especially problematic in older adults, since the

liver’s ability to diminish drugs decreases with age.
• 4)Alcohol& Insulin or Oral Diabetic Agents
An alcoholic drink can increase or prolong the effects of insulin or oral
diabetic agents (pills) and thus lead to hypoglycemia or low blood sugar.
The glucose-lowering action of alcohol can last as long as eight to 12
hours.

• In addition, certain oral diabetic medications such as Chlorpropamide

(Diabinese) can cause dizziness, flushing, and nausea when taken along
with alcohol.
Food/Nutrient Effects on Drug Action
• MAOIs and Tyramine-Containing Foods
Monoamine oxidase inhibitors are an older type of antidepressant still
prescribed, albeit less frequently, due to their serious side effects.
• “Foods containing tyramines, such as some red wines, malt beer, smoked
fish, aged cheeses, and dried fruits, can cause a hypertensive crisis or
severe and dangerous elevation in blood pressure when taken with this
class of antidepressants,”
• Monoamine oxidase inhibitors (MAOI) interact with pressor agents in
foods (tyramine, dopamine)

• Pressors are generally deaminated rapidly by MAO; MAOIs prevent the

breakdown of tyramine and other Pressors

• Significant intake of high-tyramine foods (aged cheeses, cured meats) by

patient on MAOIs can precipitate hypertensive crisis
Food/Nutrient Effects on Drug Action
• Warfarin and Vitamin K
Warfarin (Coumadin) is a blood-thinning medication that helps treat
and prevent blood clots. Eating certain foods, especially those rich in
vitamin K, can diminish warfarin’s effectiveness. The highest
concentrations of vitamin K are found in green leafy vegetables such
as kale, collards, spinach, turnip greens, Brussels sprouts, broccoli,
scallions, asparagus, and endive.
• “It’s not that patients should avoid foods that contain vitamin K,” “Rather,
they should keep their intake consistent from day to day.”

• “If a doctor tells a patient that they should lose weight

• and, start to eat more greens, their vitamin K

• intake will go up, and this will counteract

• the anticlotting action of warfarin.”

Food/Nutrient Effects on Drug Action
• Antithyroid Drugs and Iodine-Rich Foods
Antithyroid drugs are interfere with the body’s production of thyroid
hormones, reducing the symptoms of hyperthyroidism . They work by
preventing iodine absorption in the stomach. A high-iodine diet requires
higher doses of antithyroid drugs. The higher the dose of, the greater the
incidence of side effects that include rashes, and liver disease.
• The richest dietary sources of iodine are seafood and seaweed, such as kelp.
Iodine is also found in iodized salt and to a lesser extent in eggs, meat, and
dairy products.
Effect of drugs on the
nutritional status
• Drugs Can Affect Nutritional State by:
A) At the level of the Mouth:1) Drug may impair salivary flow- Drug
secreted in saliva
• 2) Drug may suppress natural oral bacteria
• 3) Drug may cause taste and smell changes
• B) At level of stomach and intestine: 1) Drug irritate stomach
• 2) Drug affect intestinal peristalsis
• 3) Drug destroy intestinal bacteria
• C) At level of CNS (Appetite changes): 1) Drug suppress appetite (e.g.
SSRI) 2) Drug increase appetite: (e.g. Tricyclic antidepressants)
Effect of drugs on the nutritional status
• drugs can affect taste and smell:
*Antineoplastic drugs: cisplatin , methotrexate, interferon.
*anti-infective drugs: clarithromycin, metronidazole.
*cardiovascular drugs: captopril
*CNS drugs: phenytoin, sumatriptan,
levodopa
Effect of drugs on the nutritional status
• Drugs that may decrease the appetite(examples):
*anti-infective: amphotericin B
*antineoplastic: bleomycin, methotrexate
*bronchodilators: theophylline
*stimulant drugs: amphetamine, phentermine
*miscellaneous: fluoxetine(Prozac), naltrexone, topiramate
Effect of drugs on the nutritional status
• Drugs that may increase the appetite(examples):
*psychotropic: alprazolam(Xanax)
*antipsychotics: risperidone
*antidepressants: imipramine, paroxetine
*anticonvulsants: gabapentin
*hormones: cortisone, testosterone, medroxyprogesterone
Examples of Drug Classes That Cause
Diarrhea
• Laxatives
• Antiretrovirals
• Antibiotics
• Antineoplastic
• + liquid medications in elixirs containing sugar
alcohols
Drugs That May Lower Glucose Levels

• Antidiabetic drugs (acarbose, glimepiride, glipizide, glyburide, insulin,

metformin, miglitol, neteglinide, pioglitizone, repaglinide, roiglitizone
• Drugs that can cause hypoglycemia: ethanol, quinine, disopyramide
(antiarrhythmic) and pentamidine isethionate (antiprotozoal)
Drugs That Raise Blood Glucose
• Antiretrovirals, protease inhibitors (amprenavir, nelfinavir, ritonavir,
saquinavir)
• Diuretics, antihypertensives (furosemide, hydrochlorothiazide,
indapamide)
• Hormones (corticosteroids, danazol, estrogen or estrogen/progesterone
replacement therapy, megestrol acetate, oral contraceptives)
• Niacin (antihyperlipidemic) baclofen, caffeine, olanzapine, cyclosporine,
interferon alfa-2a
 Medications and enteral nutrition interactions

• Most medications should not be mixed with enteral feedings; physical

incompatibilities can occur including granulation, gel formation,
separation of the feeding leading to clogged tubes
• Enteral feedings interfere with phenytoin absorption; window the
feeding around drug dose (2 hours before and after)
• Drugs put in feeding tubes may cause:
—Diarrhea
—Drug-nutrient binding
—Blocked tube
• Avoid adding drug to formula
• When drugs must be given through tube:
• Stop feeding, flush tube, give drug, flush
• Use liquid form of drug
• Avoid crushing tablets
• Be aware of potential interactions between enteral feedings and
drugs
• Example of drugs that cause granulations and gel formation: Ciprofloxacin
• Reduced bioavailability of Phenytoin when given with enteral feeding
MNT for Food-Drug Interactions
• Prospective: MNT offered when the patient first starts a drug
• Retrospective: evaluation of symptoms to determine if medical
problems might be the result of food-drug interactions
Avoiding Food-Drug Interactions:
Prospective
• When medications are initiated, patients should be provided with
complete written and verbal drug education at an appropriate reading level
including food-drug interaction information

• Patients should be encouraged to ask specific questions about their

medications and whether they might interact with each other or with foods

• Patients should read the drug label and accompanying materials provided
by the pharmacist
Avoiding Food-Drug Interactions:
Prospective
• In acute-care settings, patients receiving high risk medications should
be identified and evaluated

• Nurses should have information regarding drug-food interactions and

drug administration guidelines available at the bedside
Avoiding Food-Drug Interactions:
Prospective
• Systems should be established so that pharmacists can communicate
with food and nutrition staff regarding high risk patients
Avoiding Food-Drug Interactions:
Retrospective
• Clinicians including dietitians should obtain a full drug and diet history including
the use of OTC and dietary supplements and review potential drug-food
interactions

• A plan should be developed for dealing with potential drug-food interactions for
short and long term drug therapy

• When therapeutic goals are not met, clinicians should ask questions about how
and when drugs are being taken in relation to foods and nutritional supplements
Avoiding Food-Drug Interactions:
Retrospective
• Clinicians should evaluate whether medical problems could be the

result of drug-food interactions

• Often it may be the dietitian who is most aware of these issues