Drug food interactions in details - QA

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Contents
Contents...........................................................................................................................................1
Introduction .....................................................................................................................................2
Definitions.........................................................................................................................................4
Underlying factors:..........................................................................................................................5
Classification of drug-food interactions: .....................................................................................6
EFFECTS OF FOOD ON DRUG ..................................................................................................7
I. Pharmacokinetic interactions ........................................................................................7
II. Pharmacodynamics Interactions ................................................................................11
EFFECTS OF DRUGS ON NUTRITION STATUS...........................................................................12
Most common food drug interactions :.....................................................................................16
Grapefruit juice.......................................................................................................................16
St. John’s wort .........................................................................................................................19
Other examples ......................................................................................................................24
Alcohol and Medication Interactions........................................................................................30
 Specific Alcohol-Medication Interactions ......................................................................32
Summary of some signifiant Food-Drug Interactions...............................................................37
References:....................................................................................................................................42

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Introduction
Medicines can treat and cure many health problems. However, they must be taken
properly to ensure that they are safe and effective. Medications should be extremely
specific in their effects, have the same predictable effect for all patients, never be affected
by concomitant food or other medications, exhibit linear potency, be totally non-toxic in
any dosage and require only a single dose to affect a permanent cure. However, this ideal
drug is still to be discovered. Many medicines have powerful ingredients that interact with
the human body in different ways. Diet and lifestyle can sometimes have a significant
impact on drugs.
A drug interaction is a situation in which a substance affects the activity of a drug when
both are administered together i.e. the effects are increased or decreased, or they produce
a new effect that neither produces on its own.
Typically, interactions between drugs come to mind (drug-drug interaction). However,
interactions may also exist between drugs and foods (drug-food interactions), as well as
drugs and medicinal plants or herbs (drug-plant interactions). People taking
antidepressant drugs such as monoamine oxidase inhibitors should not take food
containing tyramine as hypertensive crisis may occur (an example of a drug-food
interaction). These interactions may occur out of accidental misuse or due to lack of
knowledge about the active ingredients involved in the relevant substances.
It is also possible for interactions to occur outside an organism before administration of
the drugs has taken place. This can occur when two drugs are mixed, for example, in a
saline solution prior to intravenous injection. Some classic examples of this type of
interaction include that thiopentone and suxamethonium should not be placed in the same
syringe and same is true for benzylpenicillin and heparin. These situations will all be
discussed under the same heading due to their conceptual similarity.
Drug interactions may be the result of various processes. These processes may include
alterations in the pharmacokinetics of the drug, such as alterations in the absorption,
distribution, metabolism, and excretion (ADME) of a drug. Alternatively, drug interactions
may be the result of the pharmacodynamic properties of the drug, e.g., additive,
synergistic, or antagonistic effects (when co-administration of a receptor antagonist and
an agonist for the same receptor) of a drug.
Drug interactions (DIs) represent an important and widely under recognized source of
medication errors.
Interactions between food and drugs may inadvertently reduce or increase the drug effect.
Some commonly used herbs, fruits as well as alcohol may cause failure of the therapy up a
point of to serious alterations of the patient’s health. The majority of clinically relevant
food-drug interactions are caused by food induced changes in the bioavailability of the
drug. Major side-effects of some diet (food) on drugs include alteration in absorption by
fatty, high protein and fiber diets.
Bioavailability is an important pharmacokinetic parameter which is correlated with the
clinical effect of most drugs. However, in order to evaluate the clinical relevance of a food-
drug interaction the impact of food intake on the clinical effect of the drug has to be
quantified as well. The most important interactions are those associated with a high risk
of treatment failure arising from a significantly reduced bioavailability in the fed state.
Such interactions are frequently caused by chelation with components in food. In addition,

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the physiological response to food intake, in particular, gastric acid secretion, may reduce
or increase the bioavailability of certain drugs.
The gastrointestinal absorption of drugs may be affected by the concurrent use of other
agents that have a large surface area upon which the drug can be absorbed, bind or chelate,
alter gastric pH,4 alter gastrointestinal motility, or affect transport proteins such as P-
glycoprotein.
A reduction only in absorption rate of a drug is seldom clinically important, whereas a
reduction in the extent of absorption will be clinically important if it results in sub
therapeutic serum levels.
Factors such as nonspecific binding, atypical kinetics, poor effector solubility, and varying
ratios of accessory proteins may alter the kinetic behavior of an enzyme and subsequently
confound the extrapolation of in vitro data to the human situation.
Coenzyme Q-10 (CoQ10) is very widely consumed by humans as a food supplement
because of its recognition by the public as an important nutrient in supporting human
health. It interferes with intestinal efflux transporter P-glycoprotein (P-gp) and as result
food-drug interactions arise. The interaction of natural products and drugs is a common
hidden problem encountered in clinical practice.
The interactions between natural products and drugs are based on the same
pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Several
fruits and berries have recently been shown to contain agents that affect drug-metabolizing
enzymes.
Grapefruit is the most well-known example, but also sevillian orange, pomelo and star fruit
contain agents that inhibit cytochrome P450 3A4 (CYP3A4), which is the most important
enzyme in drug metabolism. The study of drug-drug, food-drug, and herb-drug
interactions and of genetic factors affecting pharmacokinetics and pharmacodynamics is
expected to improve drug safety and will enable individualized drug therapy.
Drugs can show their efficacy only if administered in appropriate quantity with
appropriate combination of drugs and foods and at appropriate time. In contrast to the
easy access to information on drug-drug interactions, the information about food-drug
interaction is not always available conveniently. It is a difficult and complex problem to
accurately determine the effects of food and nutrients on a particular drug.

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Definitions
 Food/Drug Interactions:
Foods can interfere with the stages of drug action in a number of ways. The most common
effect is for foods to interfere with drug absorption. This can make a drug less effective
because less gets into the blood and to the site of action. Second, nutrients or other
chemicals in foods can affect how a drug is used in the body. Third, excretion of drugs from
the body may be affected by foods, nutrients, or other substances. With some drugs, it’s
important to avoid taking food and medication together because the food can make the
drug less effective. For other drugs, it may be good to take the drug with food to prevent
stomach irritation. Alcohol can affect many medications.
 Drug/Nutrient Interactions:
It is also possible for drugs to interfere with a person’s nutritional status. Some drugs
interfere with the absorption of a nutrient. Other drugs affect the body’s use and/or
excretion of nutrients, especially vitamins and minerals. If less of a nutrient is available to
the body because of these effects, this may lead to a nutrient deficiency. Sometimes drugs
affect nutritional status by increasing or decreasing appetite. This affects the amount of
food (and nutrients) consumed.
 Synergy and antagonism
When the interaction causes an increase in the effects of one or both of the drugs the
interaction is called a synergistic effect. An “additive synergy” occurs when the final
effect is equal to the sum of the effects of the two drugs (Although some authors argue that
this is not true synergy). When the final effect is much greater than the sum of the two
effects this is called “enhanced synergy”. This concept is recognized by the majority of
authors, although other authors only refer to synergy when there is an enhanced effect.
These authors use the term "additive effect" for additive synergy and they reserve use of
the term "synergistic effect" for enhanced synergy. The opposite effect to synergy is termed
antagonism. Two drugs are antagonistic when their interaction causes a decrease in the
effects of one or both of the drugs.
Both synergy and antagonism can both occur during different phases of the interaction of
a drug with an organism, with each effect having a different name. For example, when the
synergy occurs at a cellular receptor level this is termed agonism, and the substances
involved are termed agonists. On the other hand, in the case of antagonism the
substances involved are known as inverse agonists. The different responses of a
receptor to the action of a drug has resulted in a number of classifications, which use terms
such as "partial agonist", "competitive agonist" etc. These concepts have fundamental
applications in the pharmacodynamics of these interactions. The proliferation of existing
classifications at this level, along with the fact that the exact reaction mechanisms for many
drugs are not well understood means that it is almost impossible to offer a clear
classification for these concepts. It is even likely that many authors would misapply any
given classification.

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Underlying factors:
It is possible to take advantage of positive drug interactions. However, the negative
interactions are usually of more interest because of their pathological significance and also
because they are often unexpected and may even go undiagnosed.
By studying the conditions that favour the appearance of interactions it should be possible
to prevent them or at least diagnose them in time. The factors or conditions that predispose
or favour the appearance of interactions include:
 Old age: factors relating to how human physiology changes with age may affect the
interaction of drugs. For example, liver metabolism, kidney function, nerve
transmission or the functioning of bone marrow all decrease with age. In addition, in
old age there is a sensory decrease that increases the chances of errors being made in
the administration of drugs.
 Polypharmacy: The more drugs a patient takes the more likely it will be that some
of them will interact.
 Genetic factors: Genes synthesize enzymes that metabolize drugs. Some races have
genotypic variations that could decrease or increase the activity of these enzymes. The
consequence of this would, on occasions, be a greater predisposition towards drug
interactions and therefore a greater predisposition for adverse effects to occur. This is
seen in genotype variations in the isozymes of cytochrome P450.
 Hepatic or renal diseases: The blood concentrations of drugs that are
metabolized in the liver and / or eliminated by the kidneys may be altered if either of
these organs is not functioning correctly. If this is the case an increase in blood
concentration is normally seen.
 Serious diseases that could worsen if the dose of the medicine is reduced.
 Drug dependent factors:
 Narrow therapeutic index: Where the difference between the effective dose and
the toxic dose is small. The drug digoxin is an example of this type of drug.
 Steep dose-response curve: Small changes in the dosage of a drug produce large
changes in the drug's concentration in the patient's blood plasma.
 Saturable hepatic metabolism: In addition to dose effects the capacity to
metabolize the drug is greatly decrease.

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Classification of drug-food interactions:
Drug-nutrient interactions could be classified into one of five broad categories. The many
types of drug-nutrient interactions could thus be categorized with each having an
identified precipitating factor and an object of the interaction. In some cases, the drug is
the precipitating factor (i.e., causing changes to nutritional status), while in others the drug
is the object of the interaction (i.e., changes in drug disposition or effect result from a
nutrient, food, or nutritional status). In the event of the precipitating factor produces
significant change in the object of the interaction, drug-nutrient interactions are
considered as important. Interactions that need to be totally avoided are not common;
instead close monitoring with modification to the dosing schedules is usually all that is
necessary.

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EFFECTS OF FOOD ON DRUG
I. Pharmacokinetic interactions
Modifications in the effect of a drug are caused by differences in the absorption, transport,
distribution, metabolism or excretion of the drug. These changes are basically
modifications in the concentration of the drugs.
1- Absorption interactions:
 Reduced or delayed drug absorption:
The presence of food may decrease or delay drug absorption and that could be due to:
 The formation of insoluble complexes
 Delayed gastric emptying
 Increased viscosity due to the presence of food
Some examples of drug-food interactions that delay and reduce the
absorption of drugs
Drug Mechanism Counseling
Acetaminophen
High pectin foods act
as adsorbant and
protectant
Take on empty stomach if
not contraindicated
Digoxin
High–fiber, high–pectin
foods bind drug
Take drug same time with
relation to food, Avoid
taking with high-fiber
foods
Glipizide Mechanism unknown
Affects blood glucose;
more potent when taken
half hour before meals
Isoniazide
Food raises gastric pH
preventing dissolution
and absorption
Take on empty stomach if
tolerated
Levodopa
Drug competes with
amino acids for
absorption transport
Avoid taking drug with
high–protein foods
Methyldopa
Competitive
absorption
Avoid taking with high-
protein foods
If an orally administered drug harms the stomach lining or decomposes in the acidic
environment of the stomach, a tablet or capsule of the drug can be coated with a substance
intended to prevent it from dissolving until it reaches the small intestine. These protective
coatings are described as enteric coating. For these coatings to dissolve, they must come
in contact with the less acidic environment of the small intestine or with the digestive
enzymes there. One example is aspirin, when food delays gastric emptying this delays
aspirin absorption.
 Increased drug absorption:
Increased drug absorption due to the presence of food has been frequently reported.
Accumulated evidence suggest that more complete drug dissolution due to the presence of
food itself, or as a result of food induced gastrointestinal secretions or delayed gastric

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emptying, often has a significant positive effect on absorption, particularly for fat soluble
compounds.
 In particular, poorly water soluble drugs (e.g. griseofulvin, mebendazole and
halofantrine), when taken as a solid formulation may not enter solution readily in
the stomach. Administration of such drugs with very fatty foods can increase
bioavailability, possibly by such mechanisms as the formation of solutions in the
dietary oil.
 Bioavailability of Axetil (Ceftin), an antibiotic, is 52% after a meal and 37% in the
fasting state.
 Absorption of the antiretroviral drug saquinavir is increased twofold by food.
 Taking ketoconozole and delavirdine with orange or cranberry juice can reduce
stomach pH and increase absorption, however in the case of warfarin, patients who
are taking warfarin should limit or avoid completely drinking cranberry juice.
Some examples of drug-food interactions that accelerate the absorption of drugs
Drug Mechanism Counseling
Carbamazepine Increased bile production,
enhanced dissolution and
absorption
Dicumerol Increased bile flow, delayed gastric
emptying permits dissolution and
absorption
Take with food
Erythromycin Unknown
Griseofulvin Drug is lipid soluble, enhanced
absorption with high- fat foods.
Take with high- fat foods
Hydralazine, Labetalol
and Metaprolol
Food may reduce first-pass
extraction and metabolism
Nitrofurantoin, Phenytoin
and Propoxyphene
Delayed gastric emptying improves
dissolution and absorption
Propranolol Food may reduce first-pass
extraction and metabolism
Take with food
Spironolactone Delayed gastric emptying permits
dissolution and absorption, bile may
solubilize the drug
 Food persistence may not affect drug absorption:
Drug whose absorption is not affected by food in general
Alpramlam Cardizem
Amlodipine Cefetamet pivoxil
Bambuterol Cimetidine and ranitidine
Bromocriptine norethindrone
Brofaramine Fluvoxamine
Verapamil Ibuprofen
ethinyl estradiol Diazepam

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2- Metabolism interactions:
 CYP450: Cytochrome P450 is a very large family of hemoproteins that are
characterized by their enzymatic activity and their role in the metabolism of a large
number of drugs. Of the various families that are present in human beings the most
interesting in this respect are the 1, 2 and 3, and the most important enzymes are
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The majority of the
enzymes are also involved in the metabolism of endogenous substances, such as
steroids or sex hormones, which is also important should there be interference with
these substances. As a result of these interactions the function of the enzymes can either
be stimulated (enzyme induction) or inhibited (enzyme inhibition).
 In the case of levodopa, absorption occurs readily in both stomach and small bowel,
and food induces delay in gastric emptying. However, DOPA-decarboxylase, the
enzyme responsible for levodopa degradation, is present in gastric mucosa at high
concentration, and the net effect of delayed gastric emptying is to increase the pre-
systemic metabolism of the drug.
Fruit-drug interactions
Fruit Molecular target Drug interactions
Grapefruit inhibits CYP3A4, CYP1A2,
MRP2, OATP-B and
P-glycoprotein
calcium channel antagonist, central
nervous system modulators, HMG-
CoA reductase,
immunosuppressants, antivirals,
phosphodiesterases-5 inhibitor,
antihistamines, antiarrythmics and
antibiotics
Sevilla orange inhibits CYP3A4, P-
glycoprotein, OATP-A, OATP-
B
vinblastine, fexofenadine,
glibenclemida, atenolol,
ciprofloxacine, ciclosporine,
celiprolol, levofloxacin and
pravastatin
Tangerine stimulates CYP3A4 activity
and inhibits P-glycoprotein
nifedipine, digoxin
Grapes inhibits CYP3A4 and CYP2E1 cyclosporine
Mango inhibits CYP1A1, CYP1A2,
CYP3A1, CYP2C6, CYP2E1, P-
glycoprotein
midazolam, diclofenac,
chlorzoxazone, verapamil
Apple inhibits CYP1A1,
OATP family
Fexofenadine
Papaya inhibits CYP3A4 not documented

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Vegetable-drug interactions
Vegetable Molecular target Drug interactions
Broccoli inhibits CYP1A1, CYP2B1/2,
CYP3A4, CYP2E1, hGSTA1/2,
MRP1, MRP2, BCRP, UDP,
glucorosytransterases,
dulfotransferases, quinone
reductses
phenolsulfotransferases
induces: UDP-
glucuronosyltransferases,
(UGTs), sulfotransferases
(SULTs) and quinone
reductase (QRs)
not documented
Spinach possible inhibition of CYP1A2 heterocyclic aromatic amines
Tomato inhibits CYP1A1, CYP1B1,
UGP increases UGT and
CYP2E1
diethylnitrosamine, N-methyl- ,-N-
nitrosourea and 1,2
dimethylhydrazine
Carrot induces
phenolsulfotransferases and
ethoxycoumarin O-
deethylase ECD inhibits
CYP2E1
not documented
Red
pepper
inhibits CYP1A2, CYP2A2,
CYP3A1, CYP2C11, CYP2B1,
CYP2B2, CYP2C6
in vitro and in vivo
3- Excretion interactions
 Renal excretion:
Only the free fraction of a drug that is dissolved in the blood plasma can be removed
through the kidney. Therefore, drugs that are tightly bound to proteins are not available
for renal excretion, as long as they are not metabolized when they may be eliminated as
metabolites.
The excretion of drugs from the kidney's nephrons has the same properties as that of any
other organic solute: passive filtration, reabsorption and active secretion. In the latter
phase the secretion of drugs is an active process that is subject to conditions relating to the
saturability of the transported molecule and competition between substrates. Therefore,
these are key sites where interactions between drug and nutrition could occur. Filtration
depends on a number of factors including the pH of the urine, it having been shown that
the drugs that act as weak bases are increasingly excreted as the pH of the urine becomes
more acidic, and the inverse is true for weak acids.

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II. Pharmacodynamics Interactions
Foods may interact with medications by altering their pharmacologic actions.
 Diets high in vitamin K may cause antagonism of warfarin and decreased
therapeutic efficacy of the anticoagulant. Foods rich in vitamin K include green
leafy vegetables (kale, turnip greens, spinach and broccoli), cauliflower, chick
peas, green tea, pork liver and beef liver. Garlic can cause additive antiplatelet
eﬀect in combination with warfarin, heparin, and low molecular weight heparin
(LMWH), and cause increased risk of bleeding.
 Alcoholic beverages may increase the central nervous system depressant effects
of medications such as benzodiazepines, antihistamines, antidepressants,
antipsychotic, muscle relaxants, narcotics or any drug with sedative actions.
 An example of a food potentiating the effect of a medication is coffee, as caffeine
has additive effects on theophylline. It has been reported that caffeine increased
serum theophylline levels by 20%–30% and increased the half-life of
theophylline by decreasing clearance. Patients may complain of nervousness,
tremor or insomnia. Caffeine has some bronchodilator effects, which may
enhance the effects of theophylline. A lower dosage of theophylline may be
necessary for those patients who consume excessive quantities of coffee (more
than 6 cups daily).

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EFFECTS OF DRUGS ON NUTRITION STATUS
Some drugs can have an effect on a patient’s nutritional status. The mechanisms for these
effects are varied and are usually due to drug side effects. A drug can enhance or inhibit
nutrient bioavailability. Thus, it affects the nutritional status of individuals. For instance,
elderly people, who are taking multiple medications for a long period of time are often
found to be deficient in one or more nutrients. Other age groups, such as young children
and adolescents, are also particularly at risk.
There is a potential problem with drug-nutrient interactions in adolescents because their
nutrient needs are higher than those of adults. Pregnant women and infants are the other
groups also at particular risk. The reason of these deficiencies is not only based on the
chemical reactions between drugs and nutrients but also on the dose and duration of
treatment or exposure to the drug.
Drugs can interfere with nutrient at several sites starting from the ingestion of the food to
the final stage of excretion.
The influence of medication on overall nutritional status can be due to many factors: Drugs
can influence food intake, digestion, and absorption. Many drugs can cause anorexia, alter
taste and smell, cause nausea and vomiting, and ultimately affect overall food intake.
 Non-steroidal anti-inflammatory agents, commonly used to treat arthritis, including
aspirin, can cause irritation of the upper gastrointestinal mucosa and even cause ulcers,
this can depress appetite and produce weight loss.
 On the other hand, some anorectic drugs are used for weight loss and to treat obesity
by reducing appetite. Examples are adrenergic and serotoninergic agents, which cause
satiety, reduce appetite, and increase energy expenditure leading to weight loss. A good
example for adrenergic drugs are amphetamines that stimulate secretion of
norepinephrine and reduce food intake.
 The using of chemotherapeutic agents to treat cancer can affect growing tissues,
particularly the lining of the gastrointestinal tract (GIT). Nausea is a common side
effect and can interfere with eating. Some patients can have oral and esophageal lesions
and it can cause pain upon chewing and swallowing (odynophagia). Thus, this
formations lead to limits oral intake.
 Antibiotics can suppress commensal bacteria, and this may result in overgrowth of
other organisms such as Candida albicans. Overgrowth in the GIT may produce
malabsorption and diarrhea. Overgrowth in the mouth may result in candidiasis or
thrush, which can reduce oral intake.
 Taste and smell are very important factors that influence food intake and can
subsequently affect the nutritional status of individuals. Taste alteration (dysgeusia or
hypogeusia) due to medications is very common. Some hypoglycemic agents like
glipizide, the antimicrobials amphotericin B, ampicillin, and antiepileptic phenytoin
are among the medications that alter taste perception.
 Many drugs reduce salivation and cause dryness of the mucus membranes. This can
also inhibit oral intake.
Nausea, vomiting, diarrhea, and constipation are ubiquitous side effects associated with
most medications, so oral intake of food may be reduced due to these effects.
Because of the presence of drugs, several mechanisms can affect nutrient absorption:
Drugs can damage the intestinal absorptive surfaces including villi, microvilli, brush
border enzymes, and the transport system. Also drugs can affect the absorption of

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nutrients by changing the GI transit time or the overall GI chemical environment.
Absorption of micronutrients, vitamins and minerals, as well as macronutrients, protein
and fat, are affected by the type, dosage, and strength of some drugs.
 Many laxatives, mineral oil, and cathartic agents reduce transit time in the GI tract and
may cause steatorrhea and loss of fat-soluble vitamins, A and E, and possibly calcium
and potassium.
 Drugs containing sorbitol, such as theophylline solutions, can induce osmotic diarrhea
and so shorten the transit time.
 Antacids change the pH of the stomach and cause chelating with some minerals,
consequently reducing their absorption. Higher pH in the stomach reduces the
absorption of iron, calcium, zinc, and magnesium.
 Several groups of drugs can increase appetite and consequently lead to weight gain
examples include:
 Anticonvulsants (caramazepine and valproic acid)
 Antihistamines (cyproheptadine hydrochloride – Periactin)
 Psychotropic drugs (chlordiazepoxide hydrochloride – Librium, diazepam –
Valium, chloromazine hydrochloride – Thorazine, meprobamate – Equanil)
 Corticosteroids (cortisone, prednisone).
 Synthetic derivative of progesterone, medroxyprogesterone acetate or megestrol
acetate, used for the treatment of hormone-sensitive breast and endometrial
cancer, may increase appetite, food intake, and weight gain.
 Dronabinol also known as THC (from tetrahydracannabinols), is also used as an
appetite stimulant.
 Megesterol can enhance appetite and it is a progestin used to treat certain types
of cancer.
 The formulation of drugs in lipid emulsion (e.g. in 10% soybean), contributes to a
significant amount of additional energy intake.
 Other drugs (e.g. lorazepam, morphine, pancuronium) can change the bodyweight by
decreasing the body’s energy expenditure.
 Besides drugs specifically indicated to affect changes in appetite, some drugs may affect
appetite as a side effect:
 Several antidepressants have been observed to consistently increase or decrease
appetite.
 Several metabolic adverse effects (i.e., weight gain, hyperglycemia,
dyslipidemia) have been associated with the use of the second-generation
antipsychotics. An evaluation of a large database revealed that weight gain
(increased BMI) was significantly more likely with the use of risperidone,
quetiapine, and olanzapine compared with first-generation antipsychotic
agents, while weight gain was less likely with aripiprazole, ziprasidone, and
clozapine.
 Some of the important functions of vitamins and several minerals are being
coenzymes/cofactors in metabolic processes in the human body. As a result, certain
drugs are targeted to these coenzymes (antivitamins) in order to reduce the activity of
some enzymes in related metabolic reactions. Good examples of these drugs are:
 Vitamin folate (B6) is a cofactor for the enzyme dihydrofolate reductase, it is
necessary for nucleic acid biosynthesis and cell replication. This vitamin will be
excreted because the drugs displace it from dihydrofolate reductase to reduce
cell replication, like methotrexate (MTX) for treating leukemia and rheumatoid
arthritis.

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 The anticoagulant drug, warfarin (Coumadin) acts by preventing the conversion
of vitamin K to a useful form, thus a balance or steady state between dose of drug
and consumption of vitamin K must be achieved.
 Colchicine (gout) para-aminosalicylic acid (TB) sulfasalazine (ulcerative colitis)
trimethoprim (antibiotic) and pyrimethamine (antiprotozoal) impair
absorption of B12 or folate.
 Antibiotics can effect normal flora and cause vitamin B depletion and antibiotics
like cefamendole, cefoperazone, cefotetan can interfere with vitamin K
producing bacteria.
 Nutrient excretion and altered reabsorption mechanisms can cause drugs to
induce nutrient excretion:
 D-Penicillamine chelates with toxic metals, and with some other metals like
zinc, eliminating it via urine.
 Ethylenediaminetetra-acetic acid (EDTA) has been shown to cause urinary
excretion of zinc.
 Some diuretics, such as furosemide, ethacrynic acid, and triamterene, reduce
the reabsorption of electrolytes and minerals such as calcium, magnesium,
zinc, and increase renal excretion of these elements.
 The using of thiazide and loop diuretics can often cause sodium loss in the
urine.
 Phenothiazine antipsychotic drugs (chlorpromazine) increase excretion of
riboflavin which can lead to riboflavin deficiency in those with poor intakes
 Potassium-sparing diuretics spare potassium and magnesium loss but
augment urinary sodium loss.
 Cisplatin causes nephrotoxicity and renal magnesium wasting resulting in
acute hypomagnesemia in 90% of patients (also hypocalcemia, hypokalemia,
hypophosphatemia), may require intravenous magnesium supplementation
or post-treatment hydration and oral magnesium supplementation and that
may persist for months or years after therapy is finished.
 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 to prevent
osteoporosis.
Drug Side Effects that Affect Nutritional Status
• Appetite changes
• Oral taste and smell
• Nausea
• Dry mouth
• Gastrointestinal effects
• Organ system toxicity
• Glucose levels
Examples of drug categories that may affect appetite:
 Decrease Appetite:
 Antiinfectives

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 Antineoplastics
 Bronchodilators
 Cardiovascular drugs
 Stimulants
 Increase Appetite:
 Anticonvulsants
 Hormones
 Psychotropic drugs (Antipsychotics, Antidepressants (tricyclics, MAOIs))
1- Drugs affecting oral cavity, taste and smell
 Taste changes: cisplatin, captopril (anti-hypertensive), amprenavir (antiviral)
phenytoin (anti-convulsive), clarithromycin (antibiotic).
 Mucositis: antineoplastic drugs such as interleukin-2, paclitaxel, carboplatin.
 Dry mouth: Anticholinergic drugs (tricyclic antidepressants such as amytriptyline,
antihistamines such as diphenhydramine, antispasmodics such as oxybutynin).
2- Drugs that affect the GI tract:
 Alendronate (Fosamax) anti-osteoporosis drug, patients must sit upright 30 minutes
after taking it to avoid esophagitis.
 Aspirin or other NASAIDs can cause GI bleeding and gastritis.
 Orlistat – blocks fat absorption, can cause oily spotting, fecal urgency and
incontinence.
 Narcotic agents cause constipation.
 Drug classes that cause diarrhea:
 Laxatives
 Anti-retrovirals
 Antibiotics
 Anti-neoplastics
3- Drugs that may affect glucose levels:
 Decrease 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).
 Increase glucose levels:
 Anti-retrovirals, 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.

16
Most common food drug interactions :
Grapefruit juice
Grapefruit juice can be part of a healthful diet—most of the time. It has vitamin C and
potassium—substances your body needs to work properly. But it isn't good for you when
it affects the way your medicines work.
Grapefruit juice and fresh grapefruit can interfere with the action of some prescription
drugs, as well as a few non-prescription drugs.
This interaction can be dangerous, says Shiew Mei Huang, acting director of the Food and
Drug Administration's Office of Clinical Pharmacology. With most drugs that interact with
grapefruit juice, "the juice increases the absorption of the drug into the bloodstream," she
says. "When there is a higher concentration of a drug, you tend to have more adverse
events."
For example, if you drink a lot of grapefruit juice while taking certain statin drugs to lower
cholesterol, too much of the drug may stay in your body, increasing your risk for liver
damage and muscle breakdown that can lead to kidney failure.
Drinking grapefruit juice several hours before or several hours after you take your
medicine may still be dangerous, so it's best to avoid or limit consuming grapefruit juice
or fresh grapefruit when taking certain drugs.
Examples of some types of drugs that grapefruit juice can interact with are:
some statin drugs to lower cholesterol, such as Zocor (simvastatin), Lipitor (atorvastatin)
and Pravachol (pravastatin)
 some blood pressure-lowering drugs, such as
Nifediac and Afeditab (both nifedipine)
 some organ transplant rejection drugs, such
as Sandimmune and Neoral (both
cyclosporine)
 some anti-anxiety drugs, such as BuSpar
(buspirone)
 some anti-arrhythmia drugs, such as
Cordarone and Nexterone (both amiodarone)
 some antihistamines, such as Allegra
(fexofenadine)
Grapefruit juice does not affect all the drugs in the
categories above.

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Drugs known to interact with grapefruit juice :
Too High or Too Low Drug Levels
Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4
in the small intestine. Certain substances in grapefruit juice block the action of CYP3A4,
so instead of being metabolized, more of the drug enters the bloodstream and stays in the
body longer. The result: potentially dangerous levels of the drug in your body.
The amount of the CYP3A4 enzyme in the intestine varies from one person to another.
Some people have a lot, and others have just a little—so grapefruit juice may affect people
differently when they take the same drug.
While scientists have known for several decades that grapefruit juice can cause a
potentially toxic level of certain drugs in the body, more recent studies have found that the
juice has the opposite effect on a few other drugs. "Grapefruit juice reduces the absorption
of fexofenadine," decreasing the effectiveness of the drug. Fexofenadine (brand name
Allegra) is available in both prescription and non-prescription forms to relieve symptoms
of seasonal allergies. Fexofenadine may also be less effective if taken with orange or apple
juice, so the drug label states "do not take with fruit juices."
Why this opposite effect?
It involves the transportation of drugs within the body rather than their metabolism.
Proteins in the body known as drug transporters help move a drug into cells for absorption.
Substances in grapefruit juice block the action of a specific group of transporters. As a
result, less of the drug is absorbed and it may be ineffective.
When a drug sponsor applies to FDA for approval of a drug, the sponsor submits data on
how its drug is absorbed, metabolized and transported. "Then we can decide how to label
the drug."
FDA has required some prescription drugs to carry labels that warn against consuming
grapefruit juice or fresh grapefruit while using the drug. And the agency's current research
into drug and grapefruit juice interaction may result in label changes for other drugs as
well.

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Tips for Consumers:
 Ask your pharmacist or other health care professional if you can have fresh
grapefruit or grapefruit juice while using your medication. If you can’t, you may
want to ask if you can have other juices with the medicine.
 Read the Medication Guide or patient information sheet that comes with your
prescription medicine to find out if it could interact with grapefruit juice. Some may
advise not to take the drug with grapefruit juice. If it’s OK to have grapefruit juice,
there will be no mention of it in the guide or information sheet.
 Read the Drug Facts label on your non-prescription medicine, which will let you
know if you shouldn’t have grapefruit or other fruit juices with it. If you must avoid
grapefruit juice with your medicine, check the label of bottles of fruit juice or drinks
flavored with fruit juice to make sure they don’t contain grapefruit juice.
 Seville oranges (often used to make orange marmalade) and tangelos (a cross
between tangerines and grapefruit) affect the same enzyme as grapefruit juice, so
avoid these fruits as well if your medicine interacts with grapefruit juice.

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St. John’s wort
St John's wort (also known as Hypericum perforatum)
is a flowering plant in the family Hypericaceae. The
common name "St John's wort" may be used to refer to
any species of the genus Hypericum. Therefore,
Hypericum perforatum is sometimes called "common St
John's wort" or "perforate St John's wort" in order to
differentiate it. Historically, St. John’s wort has been
used for a variety of conditions, including kidney and
lung ailments, insomnia and to aid wound healing. Now
it is a medicinal herb with antidepressant activity and
potent anti-inflammatory properties as an arachidonate
5-lipoxygenase inhibitor and COX-1 inhibitor.
1- St John’s wort is known to affect several cytochrome P450 isoenzymes and this
accounts for the wide range of drugs with which St John’s wort has been reported to
interact. The following is a list of cytochrome P450 isoenzymes that have been assessed
with St John’s wort in a clinical setting:
 CYP3A4: the main clinically relevant effect of St John’s wort on cytochrome P450 is the
induction of CYP3A4. This has been shown to be related to the constituent, hyperforin.
Products vary in their hyperforin content; preparations with a high-hyperforin content,
given for a long period of time, will induce CYP3A4 activity, and therefore decrease the
levels of drugs metabolised by CYP3A4, by a greater extent than preparations
containing low-hyperforin levels taken for a shorter period of time.
Conventional drugs are often used as probe substrates in order to establish the activity
of another drug on specific isoenzyme systems.
 CYP2C19: there are some clinical reports suggesting that St John’s wort induces
CYP2C19.
 CYP2C8: St John’s wort may induce CYP2C8.
 CYP2C9: St John’s wort may induce CYP2C9, but the mechanism for these interactions
is not conclusive because not all CYP2C9 substrates have been found to interact.
 CYP2E1: St John’s wort may induce CYP2E1 but the general clinical importance of this
is unclear.
 CYP1A2: St John’s wort is also thought to be an inducer of CYP1A2 as levels of caffeine
and theophylline, both of which are CYP1A2 substrates, have been reduced by St John’s
wort. However, the general clinical importance of this is unclear as other studies have
found no clinically significant effect on these drugs. This may be because St John’s wort
only has a minor inducing effect on CYP1A2, which may depend on the level of exposure
to hyperforin.
 CYP2D6: St John’s wort does not appear to affect the activity of CYP2D6 to a clinically
relevant extent.
2- P-glycoprotein:
St John’s wort is known to affect P-glycoprotein activity, especially intestinal P-
glycoprotein, and it is generally thought that inhibition takes place initially, and briefly,
but is followed by a more potent and longer-acting induction. It is the induction that leads
to the clinically relevant drug interactions of St John’s wort that occur as a result of this
mechanism. Hyperforin is implicated as the main constituent responsible for the effect.

20
3- Serotonin syndrome St John’s wort inhibits the reuptake of 5-hydroxytryptamine (5-
HT, serotonin) and this has resulted in a pharmacodynamic interaction, namely the
development of serotonin syndrome with conventional drugs that also have
serotonergic properties
Interactions overview
St John’s wort is known to interact with many conventional drugs because of its ability to
induce the activity of CYP3A4 and P-glycoprotein, which are involved in the metabolism
and distribution of the majority of drugs. Hyperforin is the active constituent believed to
be central to the inducing effects of St John’s wort. As St John’s wort preparations and
dose regimens are varied, the amount of hyperforin exposure will also vary a great deal,
which makes predicting whether an interaction will occur, and to what extent, difficult.
St John’s wort interaction with Antidiabetics:
St John’s wort modestly decreases the AUC of gliclazide and
rosiglitazone. Pioglitazone and repaglinide are similarly metabolised and
may therefore be expected to interact similarly. St John’s wort does not
affect the metabolism of tolbutamide.
Mechanism:
 Gliclazide is a substrate of the cytochrome P450 isoenzyme CYP2C9
and St. John’s wort induces this isoenzyme, thereby increasing the
metabolism of gliclazide and reducing its levels.
 Tolbutamide, another CYP2C9 substrate, was unaffected by St John’s wort suggests
that other factors may be involved.
 Rosiglitazone is known to be metabolised principally by the cytochrome P450
isoenzyme CYP2C8, and it was therefore concluded that St John’s wort induces this
isoenzyme.
St John’s wort interaction with Antiepileptics:
St John’s wort modestly increased the clearance of single-dose carbamazepine, but had no
effect on multiple-dose carbamazepine pharmacokinetics. St John’s wort increased the
clearance of mephenytoin by about 3-fold and is predicted to reduce the blood levels of
phenytoin and phenobarbital.
Mechanism:
 St John’s wort is a known inducer of CYP3A4, and the results with single-dose
carbamazepine are as predicted. However, carbamazepine is also an inducer of
CYP3A4, and induces its own metabolism (autoinduction). It is suggested that St
John’s wort is not sufficiently potent an inducer to further induce carbamazepine
metabolism when autoinduction has occurred, and therefore a small interaction is seen
with single doses but no interaction is seen with multiple doses.
 Mephenytoin is a substrate of CYP2C19 and St John’s wort appears to induce this
isoenzyme.

21
St John’s wort interaction with Benzodiazepines:
Long-term use of St John’s wort decreases the plasma levels of alprazolam, midazolam and
quazepam. St John’s wort preparations taken as a single dose, or containing low-
hyperforin levels, appear to have less of an effect.
Mechanism:
 Alprazolam, midazolam and quazepam are substrates of the cytochrome P450
isoenzyme CYP3A4. St John’s wort appears to induce CYP3A4, thus increasing the
metabolism of oral midazolam, alprazolam1 and quazepam, and reducing the
bioavailability of these benzodiazepines.
St John’s wort interaction with Caffeine:
Studies suggest that St John’s wort increases the metabolism of caffeine.
Mechanism:
 These studies investigated whether St John’s wort had any effect on the cytochrome
P450 isoenzyme CYP1A2 by which caffeine is metabolized.
St John’s wort interaction with Calcium-channel blockers:
St John’s wort significantly reduces the bioavailability of nifedipine and verapamil. Other
calcium-channel blockers would be expected to interact similarly.
Mechanism:
 It appears that St John’s wort decreased the bioavailability of both nifedipine and
verapamil by inducing their metabolism by the cytochrome P450 isoenzyme CYP3A4 in
the gut.
St John’s wort interaction with Chlorzoxazone:
St John’s wort increases the clearance of chlorzoxazone.
Mechanism:
 It appears that St John’s wort increases the clearance of chlorzoxazone by inducing its
metabolism by the cytochrome P450 isoenzyme CYP2E1.
St John’s wort interaction with Cyclosporine:
Marked reductions in ciclosporin blood levels and transplant rejection can occur within a
few weeks of starting St John’s wort.
Mechanism:
 St John’s wort is induces the cytochrome P450 isoenzyme CYP3A4 by which
cyclosporine is metabolized. Concurrent use therefore reduces cyclosporine levels. It has
also been suggested that St John’s wort affects cyclosporine reabsorption by inducing
the drug transporter protein, P-glycoprotein, in the intestine.
St John’s wort interaction with Cimetidine:
Cimetidine does not significantly alter the metabolism of the constituents of St John’s
wort.

22
Mechanism:
 Cimetidine is an inhibitor of the cytochrome P450 isoenzymes CYP3A4, CYP1A2 and
CYP2D6. This study suggests that St John’s wort is not significantly metabolised by
these isoenzymes.
St John’s wort interaction with Digoxin:
Digoxin toxicity occurred in a patient taking digoxin when he stopped taking St John’s
wort. There is good evidence that some preparations of St John’s wort can reduce the levels
of digoxin by about one-quarter to one-third.
Mechanism:
 St John’s wort, and specifically hyperforin has been shown to increase the activity of the
P-glycoprotein drug transporter protein in the intestines, which reduces the absorption
of digoxin
St John’s wort interaction with Imatinib:
St John’s wort lowers serum imatinib levels.
Mechanism
 St John’s wort induces intestinal CYP3A4 and it therefore also reduces imatinib levels.
St John’s wort interaction with NNRTIs:
There is some evidence to suggest that St John’s wort may decrease the levels of
nevirapine. Delavirdine and efavirenz would be expected to be similarly affected.
Mechanism
 This finding supports predictions based on the known metabolism of the NNRTIs
delavirdine, efavirenz and nevirapine by the cytochrome P450 isoenzyme CYP3A4, of
which St John’s wort is a known inducer
St John’s wort interaction with Opioids:
St John’s wort reduces the plasma concentrations of methadone and withdrawal
symptoms may occur.
Mechanism:
 St John’s wort is metabolised in the liver and induces the cytochrome P450 enzyme
CYP3A4, and so could affect plasma levels of drugs metabolised in this way, such as
methadone.
St John’s wort interaction with Protease inhibitors:
St John’s wort causes a marked reduction in the serum levels of indinavir, which may result
in HIV treatment failure. Other protease inhibitors, whether used alone or boosted by
ritonavir, are predicted to interact similarly
Mechanism:

23
 Not fully understood, but it seems highly likely that St John’s wort induces the activity
of the cytochrome P450 isoenzyme CYP3A4, thereby increasing the metabolism of
indinavir and therefore reducing its levels.
St John’s wort interaction with Proton pump inhibitors:
St John’s wort induces the metabolism of omeprazole, and this might result in reduced
efficacy. Other proton pump inhibitors are likely to be similarly affected.
Mechanism:
 St John’s wort increases the metabolism of omeprazole by inducing both CYP2C19 and
CYP3A4.
St John’s wort interaction with SSRIs:
Cases of severe sedation, mania and serotonin syndrome have been reported in patients
taking St John’s wort with SSRIs.
Mechanism:
 A pharmacodynamic interaction may occur between St John’s wort and venlafaxine
because they can both inhibit the reuptake of 5-hydroxytryptamine (serotonin).
St John’s wort interaction with Statins:
St John’s wort modestly decreases the plasma levels of atorvastatin and simvastatin, but
not pravastatin.
Mechanism:
 The reason for this interaction is unknown, but St John’s wort may reduce the levels of
simvastatin and its metabolite, and atorvastatin, by inducing the cytochrome P450
isoenzyme CYP3A4 or by having some effect on P-glycoprotein.
St John’s wort interaction with Tricyclic antidepressants:
The plasma levels of amitriptyline and its active metabolite, nortriptyline, are modestly
reduced by St John’s wort.
Mechanism:
 Not fully understood. St John’s wort is known to induce the activity of the cytochrome
P450 isoenzyme CYP3A4, which is a minor route of metabolism of the tricyclic
antidepressants. However, the tricyclics are predominantly metabolised by CYP2D6, so
an effect on CYP3A4 is unlikely to lead to a clinically relevant reduction in their levels.
St John’s wort interaction with Warfarin and related drugs:
St John’s wort can cause a moderate reduction in the anticoagulant effects of
phenprocoumon and warfarin.
Mechanism: Uncertain, but it is suggested that the St John’s wort increases the metabolism
and clearance of the anticoagulants possibly by induction of cytochrome P450 isoenzyme
CYP3A4, and possibly also CYP2C9, as both R- and S-warfarin were affected.

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Other examples
Carbohydrates:
The impact of carbohydrates on drug metabolism is conflicting. It is known that high-
carbohydrate diets may induce the expression of several glycolytic and lipogenic hepatic
enzymes, but some suggest that carbohydrates have little impact on drug metabolism.
However, noted that antipyrine and theophylline metabolism decreased in carbohydrate-
supplemented diets but increased in the protein-enriched diet, suggesting that
carbohydrates and protein have opposite effects on oxidative drug metabolism. Although
many medications are often given to children in a sugar syrup, little research has been
done on its effect on disposition and action. Some studies suggested that dietary carb
ohydrates and fat may significantly influence the hepatic drug-metabolizing enzymes.
Protein:
Several investigators have reported that medications that undergo extensive first-pass
effect, such as propranolol, metoprolol and lidocaine, can have enhanced bioavailability
after a high-protein meal owing to enhanced hepatic blood flow. High-extraction drugs can
then rapidly pass through the liver, allowing higher drug concentrations in the systemic
circulation. A decrease in dietary protein depresses creatinine clearance and renal plasma
flow. Specific dietary proteins can also impact a response to a medication. One of the
classic examples is that of the monoamine oxidase inhibitor (MAOI) drug class and the
amino acid tyramine that is contained in aged cheeses, pickled/smoked meats, fermented
foods, and red wines. Tyramine is an indirect sympathomimetic amine that releases
norepinephrine from the adrenergic neurons, causing a significant pressor response.
Typically, tyramine is metabolized by the enzyme monoamine oxidase before any
significant increases in blood pressure are seen. If the enzyme is blocked, however, severe
and potentially fatal rises in blood pressure can occur when tyramine-rich foods are
ingested.
Other medications, such as the oxazolidinone antibiotic, linezolid, also have MAOI
properties and patients should avoid ingesting large amounts of tyramine while being
treated with this antibiotic.
Dietary protein also affects the renal tubular transport of certain compounds, although the
mechanism by which this occurs is still not understood. The binding of dietary proteins to
a drug may underscore changes in bioavailability after a protein meal. For example
increases in both the maximum concentration and area under the curve are seen in
patients receiving gabapentin. This enhanced absorption was attributed to trans-
simulation, a carrier-mediated process in which increased intestinal luminal amino acid

25
concentrations result in an up-regulation and/or increased activity of the L-amino acid
transporter.
Dietary fat:
Lipids are an essential part of cell membrane structure and are involved in many of the
normal enzymatic activities located within the cell membrane. Diets that are deficient in
fat or essential fatty acids decrease the activity of the enzyme systems responsible for the
metabolism of nutrients. Plasma free fatty acid levels become elevated after consumption
of a high-fat meal, increasing the potential to become bound to plasma albumin, and
subsequently displace albumin bound drugs, increasing the risk of drug toxicity.
Dietary fats along with food-stimulated secretions (eg, bile salts) may facilitate the
solubility of lipophilic compounds. This may contribute to a reduction in the extent of first
past metabolism due to enhanced splanchnic blood flow. Ingestion of diets high in fat has
been associated with the induction of CYP2E1. The extent to which this enzyme is up-
regulated is dependent upon the type of fat. Polyunsaturated fats such as corn and
menhaden oils appear to have the greatest influence in comparison to lard or olive oils.
This can result in enhanced peroxidation of the polyunsaturated fatty acid substrates and
contribute to free radical production. The rate of gastric emptying is also influenced by the
fat content of a meal. Fat retards gastric emptying to a greater degree than does protein or
carbohydrate.
The antiviral agent zidovudine is also impacted by dietary fat.
When administered orally, its absorption is reduced when the
drug is taken with a high-fat meal in comparison with when
taken in the fasted state. It is recommended that zidovudine
be taken on an empty stomach to achieve peak serum
concentrations.
High-fat, high-cholesterol meals can sharply reduce the effect
of ACE inhibitors such as enalapril, as well as statins and other
cholesterol medications.

26
Minerals:
Some medications, notably beta blockers such as metoprolol that are used to treat high
blood pressure, are greatly inhibited by high levels of calcium or sodium at a meal. Those
nutrients, while necessary in their own right, bind to the
medication and decrease its availability to the body. Others
like tetracycline and ciprofloxacin are markedly reduced by
milk and other dairy products, because the calcium in the
milk binds the antibiotic due to their chelation property that
lead to insoluble complex that prevents gut absorption as
well as supplemental magnesium, iron, or zinc will decrease
these drugs absorption
Vegetables:
Diets rich in vegetables and fruit may also impact the response to medications. Both serve
as sources of trace minerals that are contained in metalloenzymes, including several
antioxidants. Many plants contain flavonoids, isothiocyanates, and allyl sulfides that are
potent modulators of the cytochrome monoxygenase system.
Phyotochemicals are linked with the modulation of a variety of metabolic pathways. The
most frequently sources include cruciferous vegetables, citrus juices, and spices. Dietary
supplements and herbs are also associated with this category.
There are five major families of phytochemicals: carotinoids (eg, beta carotene, lycopene),
alkaloids, phenolics (include flavonoids, coumarins, tannins), nitrogen compounds, and
sulfur compounds (eg, isothiocyanates, allylic sulfur).
Recent research has focused on how vegetables and fruits can influence a variety of
enzymatic pathways. Typically induction of these enzyme systems is rapid and plateaus
within 5 days of continued daily ingestions of the food with the enzyme inducing capacity.8
Cruciferous vegetables, including brussels sprouts, cabbage, turnips, broccoli, cauliflower,
and spinach, contain indols that induce arylhydrocarbon hydroxylase enzyme activity as
well as the conjugation of phenacetin and acetaminophen.
Potatoes, tomatoes, and eggplant contain natural insecticide compounds called
solanaceous glycoalkaloids that even in small amounts may greatly slow the metabolism
of muscle relaxants and anesthetic agents such as suxamethonium, mivacurium, and
cocaine. Cooking does not reduce them and they may remain in the body for several days
after ingestion. Solanaceous glycoalkaloids inhibit butyryl cholinesterase, which breaks
down many anesthetic agents and cetylcholinesterase, which breaks down acetylcholine.

27
Insoluble fibers:
High-fiber foods can have unpredictable effects on the absorption of medications. For
example, insoluble dietary fiber, the kind found in bran or brown rice, can seriously inhibit
body's absorption of the heart medication digoxin. Whole grains can also take a long time
to move through digestive tract and that means medications which is been taken with or
just before the meal can spend longer than they should in the high-acid environment of
the stomach, and their effectiveness can be impaired by the time they reach the intestine.
Soluble fibers and gelling agents:
Soluble fiber is the kind found in oatmeal and in fiber supplements such as psyllium. It
forms a sticky gel in the presence of moisture, which immobilizes nutrients and
medications in the digestive system and slows their absorption, it can seriously reduce the
absorption of many antibiotics and other drugs such as warfarin. Soluble fiber and closely
related gelling agents such as guar gum and xanthan gum, often found in gluten-free foods,
can also slow absorption of many common medications.
Very low calorie diets:
In diets involving severe protein-energy restriction, such as extreme slimming diets, the
metabolism of drugs may be affected in one of two ways.
First, tissue protein is catabolized and used as an energy source, thus reducing the
availability of amino acids for protein synthesis, which in turn reduces the amount of
enzymes available for drug metabolism.
Second, endogenous substrates derived from carbohydrate and protein such as
glucuronide, sulfate, and glycine could also compete for the tissue needs for these nutrients
and that of the drug metabolism.

28
Eating habits, especially among dieters that omits or severely restrict whole categories of
foods, have a negative impact on micronutrient status. Diets that eliminate all animal foods
have been associated with other vitamin deficiencies including vitamin C. Moreover,
skipping meals and fad diets to lose weight frequently compromise micronutrient intake.
It should be routinely assumed that it is extremely difficult to meet all the requirements at
intakes of less than 1,200 calories per day.
Patients with very low calorie diet weight loss have improved hyperinsulinism as a result
of a reduction in basal insulin production as well as enhanced hepatic insulin extraction.
Moreover, it is thought the weight loss through very low calorie diet lowers the hepatic
glucuronidation of drugs leading to higher plasma concentrations of the affected drugs.
Other dietary restrictions:
In addition to caloric restriction, restriction of other dietary components can also impact
drug response.
In patients who have sodium restricted diets, there is an increased risk of acute renal
failure if these same patients are given concomitant angiotensin-converting enzyme
inhibitors (ACE inhibitors) or non-steroidal anti-inflammatory agents (NSAIDS).
There is enhanced nephrotoxicity in patients who are sodium depleted and are given
cyclosporine or tacrolimus. Sodium restriction can also increase the renal tubular
absorption of lithium, leading to toxicity. Patients receiving aminoglycosides,
amphotericin, cisplatin, or radiocontrast media in conjunction with a low-sodium diet
have an increased risk for hemodynamic nephrotoxic and ischemic acute renal failure. For
reasons still not known, the efficacy of calcium channel blockers is reduced in patients on
a sodium-restricted diet.
Vegetarianism:
Drug metabolism among vegetarians will vary dramatically depending on the protein
intake. Most research has focused on Asian vegetarians in which the half-lives of drugs
that underwent significant hepatic metabolism (antipyrine, acetaminophen and
phenacetin) were significantly longer than in nonvegetarians.
Vegetarian diets are also associated with lower circulating concentrations of sex steroids
hormones, increased fecal excretion of estrogens and different hormonal profiles in
comparison to individuals consuming an omnivorous diet. Vegetable intake may influence
total body estrogen load via the modulation of CYP enzymes involved in estrogen
metabolism. CYP13C, found in cruciferous vegetables, can increase estrogen
hydroxylation.
Impact of beverage type on drug bioavailability:
The term beverage refers to any drinkable liquid other than plain water. They are typically
classified as caffeinated, alcoholic, milk-based, mineral waters, or fruit/vegetables juices.
Depending upon the type of fluid taken with a medication, drug absorption may be
affected.
Mixing drugs with fruit juices or other beverages to mask their taste may impact
absorption due to changes in gastric pH.
Dairy products decrease the absorption of tetracyclines and reduce their bioavailability
due to the formation of insoluble chelates between the drug and the calcium present in the

29
beverage. Similar decreases in bioavailability were noted when fluoride tablets are taken
with milk.
Tannins present in teas may impair iron absorption.
Alcoholic beverages reduce the absorption of folic acid, cyanocobalamin, and magnesium.
Soft drinks, such as colas, may decrease drug absorption for a variety of reasons. The
phosphoric acid and sugar present in these drinks can slow gastric emptying and the
tendency to serve them chilled may also reduce the rate of blood flow within the intestines.
Moreover, the carbonation may increase mixing and possibly motility. Interestingly, the
acidic pH of cola beverages can be used to optimize clinical responses of both ketoconazole
and itraconazole in patients with gastric hypochlorhydria, such those patients with AIDS
gastropathy. The effects of grapefruit juice on drug disposition have been discussed
separately.
Liquorice:
Liquorice contain glycyrrhizin (glycyrrhizinic or glycyrrhizic
acid) which is hydrolyzed in the intestine to pharmacologically
active compound glycyrrhetic acid which inhibit 11
betahydroxysteroid dehydrogenase. This increase cortisol in
kidney and act as aldosterone (fluid retention, hypokalemia,
hypertension), so Liqourice should not be administrated with
antihypertensive drugs.
Iodine-rich foods:
Anti-thyroid drugs are compounds that interfere with the body’s production of thyroid
hormones, thereby reducing the symptoms of hyperthyroidism. Anti-thyroid drugs work
by preventing iodine absorption in the stomach. A high-iodine diet requires higher doses
of anti-thyroid drugs. The higher the dose of anti-thyroid drugs, the greater the incidence
of side effects that include rashes, hives, and liver disease.
The richest dietary sources of iodine are
seafood and seaweed, such as kelp and
nori. Iodine is also found in iodized salt
and to a lesser extent in eggs, meat, and
dairy products.

30
Alcohol and Medication Interactions
Most people who consume alcohol, whether in moderate or large quantities, also take
medications, at least occasionally. As a result, many people ingest alcohol while a
medication is present in their body or vice versa. A large number of medications—both
those available only by prescription and those available over the counter (OTC)—have the
potential to interact with alcohol. Those interactions can alter the metabolism or activity
of the medication and/or alcohol metabolism, resulting in potentially serious medical
consequences.
For example, the sedative effects of both alcohol and sedative medications can enhance
each other (i.e., the effects are additive), thereby seriously impairing a person’s ability to
drive or operate other types of machinery. Most studies assessing alcohol medication
interactions focus on the effects of chronic heavy drinking.
Relatively limited information is available, however, on medication interactions resulting
from moderate alcohol consumption (i.e., one or two standard drinks 1 per day).
Researchers, physicians, and pharmacists must therefore infer potential medication
interactions at moderate drinking levels based on observations made with heavy drinkers.
In addition, moderate alcohol consumption may directly influence some of the disease
states for which medications are.

31
Common Alcohol-Medication Interactions:
Mechanisms of Alcohol-Medication Interactions
Interactions between alcohol and a medication can occur in a variety of situations that
differ based on the timing of alcohol and medication consumption. For example, such
interactions can occur in people who consume alcohol with a meal shortly before or after
taking a medication or who take pain medications after drinking to prevent a hangover.
Alcohol-medication interactions fall into two general categories: pharmacokinetic and
pharmacodynamic.
- Pharmacokinetic interactions are those in which the presence of alcohol directly
interferes with the normal metabolism of the medication. This interference can take two
forms, as follows:
 The breakdown and excretion of the affected medications are delayed, because the
medications must compete with alcohol for breakdown by cytochrome P450. This
type of interaction has been described mostly for metabolic reactions involving
CYP2E1, but it also may involve CYP3A4 and CYP1A2.
 The metabolism of the affected medications is accelerated, because alcohol enhances
the activity of medication-metabolizing cytochromes. When alcohol is not present
simultaneously to compete for the cytochromes, increased cytochrome activity results
in an increased elimination rate for medications that these enzymes metabolize.
- Pharmacodynamic alcohol-medication interactions do not involve enzyme inhibition or
activation, but rather refer to the additive effects of alcohol and certain medications. In
this type of interaction, which occurs most commonly in the central nervous system
(CNS), alcohol alters the effects of the medication without changing the medication’s
concentration in the blood. With some medications (e.g., barbiturates and sedative
medications called benzodiazepines), alcohol acts on the same molecules inside or on the
surface of the cell as does the medication. These interactions may be synergistic—that is,
the effects of the combined medications exceed the sum of the effects of the individual
medications. With other medications (e.g., antihistamines and antidepressants) alcohol
enhances the sedative effects of those medications but acts through different
mechanisms from those agents.

32
 Specific Alcohol-Medication Interactions
This section describes different classes of medications and their interactions with alcohol.
The potential for the occurrence and relevance of alcohol-medication interactions in
moderate drinkers may differ, however, between pharmacokinetic and pharmacodynamic
interactions. The number of potential pharmacokinetic interactions with alcohol is great,
because the various cytochrome P450 enzymes metabolize many medications. However,
many of the pharmacokinetic interactions discussed here were first discovered in heavy
drinkers or alcoholics or were studied in animals given large alcohol doses in their diet.
Although the potential for such effects certainly exists even after low alcohol consumption,
researchers have not yet demonstrated the occurrence and relevance of those effects in
moderate drinkers. Conversely, pharmacodynamic interactions can occur with
intermittent alcohol consumption and even after a single episode of drinking. Accordingly,
those interactions clearly pertain to moderate drinkers.
 Antibiotics:
The package inserts for most antibiotics include a warning for patients to avoid using
alcohol with those medications. The rationale for these warnings is not entirely clear,
however, because only a few antibiotics appear to interact with alcohol. For example,
although some antibiotics induce flushing, most antibiotics do not. The antibiotic
erythromycin may increase alcohol absorption in the intestine (and, consequently,
increase BALs) by accelerating gastric emptying. Furthermore, people taking the
antituberculosis drug isoniazid should abstain from alcohol, because isoniazid can cause
liver damage, which may be exacerbated by daily alcohol consumption. Aside from these
effects, however, moderate alcohol consumption probably does not interfere with
antibiotic effectiveness. Possibly, concerns regarding the concurrent use of alcohol and
antibiotics grew from research findings indicating that heavy alcohol use can impair the
function of certain immune cells and that alcoholics are predisposed to certain infections.
These effects, however, are unlikely to occur in moderate drinkers.
 Antidepressants
Several classes of antidepressant medications exist, including tricyclic antidepressants
(TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase (MAO)
inhibitors, and atypical antidepressants. These classes differ in their mechanism of action
in that they affect different brain chemicals. All types of antidepressants, however, have
some sedative as well as some stimulating activity. TCAs with a higher ratio of sedative to-
stimulant activity (i.e., amitriptyline, doxepin, maprotiline, and trimipramine) will cause
the most sedation. Alcohol increases the TCAs’ sedative effects through pharmacodynamic
interactions. In addition, alcohol consumption can cause pharmacokinetic interactions
with TCAs. For example, alcohol appears to interfere with the first-pass metabolism of
amitriptyline in the liver, resulting in increased amitriptyline levels in the blood. In
addition, alcohol-induced liver disease further impairs amitriptyline breakdown and
causes significantly increased levels of active medication in the body (i.e., increased
bioavailability). High TCA levels, in turn, can lead to convulsions and disturbances in heart
rhythm. SSRIs (i.e., fluvoxamine, fluoxetine, paroxetine, and sertraline), which are
currently the most widely used antidepressants, are much less sedating than are TCAs. In
addition, no serious interactions appear to occur when these agents are consumed with
moderate alcohol doses. In fact, SSRIs have the best safety profile of all antidepressants,
even when combined in large quantities with alcohol (e.g., in suicide and overdose
situations). Conversely, people taking MAO inhibitors or atypical antidepressants can

33
experience adverse consequences when simultaneously consuming alcohol. Thus, MAO
inhibitors (e.g. phenelzine and tranylcypromine) can induce severe high blood pressure if
they are consumed together with a substance called tyramine, which is present in red wine.
Accordingly, people taking MAO inhibitors should be warned against drinking red wine.
The atypical antidepressants (i.e., nefazodone and trazodone) may cause enhanced
sedation when used with alcohol.
 Antihistamines
These medications, which are available both by prescription and OTC, are used in the
management of allergies and colds. Antihistamines may cause drowsiness, sedation, and
low blood pressure (i.e., hypotension), especially in elderly patients. Through
pharmacodynamic interactions, alcohol can substantially enhance the sedating effects of
these agents and may thereby increase, for example, a person’s risk of falling or impair his
or her ability to drive or operate other types of machinery. As a result of these potential
interactions, warning labels on OTC antihistamines caution patients about the possibility
of increased drowsiness when consuming the medication with alcohol. Newer
antihistamines (i.e., certrizine and loratidine) have been developed to minimize
drowsiness and sedation while still providing effective allergy relief. However, these newer
medications may still be associated with an increased risk of hypotension and falls among
the elderly, particularly when combined with alcohol. Consequently, patients taking
nonsedating antihistamines still should be warned against using alcohol.
 Barbiturates
These medications are sedative or sleep-inducing (i.e., hypnotic) agents that are frequently
used for anesthesia. Phenobarbital, which is probably the most commonly prescribed
barbiturate in modern practice, also is used in the treatment of seizure disorders.
Phenobarbital activates some of the same molecules in the CNS as does alcohol, resulting
in pharmacodynamic interactions between the two substances. Consequently, alcohol
consumption while taking phenobarbital synergistically enhances the medication’s
sedative side effects. Patients taking barbiturates therefore should be warned not to
perform tasks that require alertness, such as driving or operating heavy machinery,
particularly after simultaneous alcohol consumption. In addition to the pharmacodynamic
interactions, pharmacokinetic interactions between alcohol and phenobarbital exist,
because alcohol inhibits the medication’s breakdown in the liver. This inhibition results in
a slower metabolism and, possibly, higher blood levels of phenobarbital. Conversely,
barbiturates increase total cytochrome P450 activity in the liver and accelerate alcohol
elimination from the blood. This acceleration of alcohol elimination probably does not
have any adverse effect.
 Benzodiazepines
Like barbiturates, benzodiazepines (BZDs) are classified as sedative-hypnotic agents and
act through the same brain molecules as do barbiturates. Accordingly, as with barbiturates,
concurrent consumption of BZDs and moderate amounts of alcohol can cause synergistic
sedative effects, leading to substantial CNS impairment. It is worth noting that both
barbiturates and benzodiazepines can impair memory, as can alcohol. Consequently, the
combination of these medications with alcohol would exacerbate this memory-impairing
effect. In fact, this effect sometimes isexploited by mixing alcoholic beverages with BZDs,
such as the rapid-acting flunitrazepam, an agent implicated in date rape. In addition, the
metabolism of certain BZDs involves cytochrome P450, leading to the alcohol-induced
changes in metabolism described earlier in this article.

34
 Histamine H 2 Receptor Antagonists (H2RAs)
As mentioned earlier in this article, H2RAs (e.g., cimetidine, ranitidine, nizatidine, and
famotidine), which reduce gastric acid secretion, are used in the treatment of ulcers and
heartburn. These agents reduce ADH activity in the stomach mucosa, and cimetidine also
may increase the rate of gastric emptying. As a result, alcohol consumed with cimetidine
undergoes less first-pass metabolism, resulting in increased BALs. For example, in a study
of people who consumed three or four standard drinks over 135 minutes while taking
cimetidine, BALs rose higher and remained elevated for a longer period of time than in
people not taking cimetidine. Not all H2RAs, however, exert the same effect on BALs when
taken with alcohol. Thus, cimetidine and ranitidine have the most pronounced effect,
nizatidine has an intermediate effect, and famotidine appears to have no effect (i.e.,
appears not to interact with alcohol). In addition, because women generally appear to have
lower first-pass metabolism of alcohol, they may be at less risk for adverse interactions
with H2RAs.
 Muscle Relaxants
Several muscle relaxants (e.g., carisoprodol, cyclobenzaprine, and baclofen), when taken
with alcohol, may produce a certain narcotic-like reaction that includes extreme weakness,
dizziness, agitation, euphoria, and confusion. For example, carisoprodol is a commonly
abused and readily available prescription medication that is sold as a street drug. Its
metabolism in the liver generates an anxiety-reducing agent that was previously marketed
as a controlled substance (meprobamate). The mixture of carisoprodol with beer is popular
among street abusers for creating a quick state of euphoria.
 Nonnarcotic Pain Medications and Anti-Inflammatory Agents
Many people frequently use nonnarcotic pain medications and anti-inflammatory agents
(e.g., aspirin, acetaminophen, or ibuprofen) for headaches and other minor aches and
pains. In addition, arthritis and other disorders of the muscles and bones are among the
most common problems for which older people consult physicians. Nonsteroidal anti-
inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen, indomethacin, and diclofenac)
and aspirin are commonly prescribed or recommended for the treatment of these disorders
and are purchased OTC in huge amounts. Several potential interactions exist between
alcohol and these agents, as follows:
• NSAIDs have been implicated in an increased risk of ulcers and gastrointestinal
bleeding in elderly people. Alcohol may exacerbate that risk by enhancing the ability of
these medications to damage the stomach mucosa.
• Aspirin, indomethacin, and ibuprofen cause prolonged bleeding by inhibiting the
function of certain blood cells involved in blood clot formation. This effect also appears
to be enhanced by concurrent alcohol use.
• Aspirin has been shown to increase BALs after small alcohol doses, possibly by
inhibiting first-pass metabolism.
An important pharmacokinetic interaction between alcohol and acetaminophen can
increase the risk of acetaminophen-related toxic effects on the liver. Acetaminophen
breakdown by CYP2E1 (and possibly CYP3A) results in the formation of a toxic product
that can cause potentially life-threatening liver damage. As mentioned earlier, heavy
alcohol use enhances CYP2E1 activity. In turn, enhanced CYP2E1 activity increases the
formation of the toxic acetaminophen product. To prevent liver damage, patients generally

35
should not exceed the maximum doses recommended by the manufacturers (i.e., 4 grams,
or up to eight extra-strength tablets of acetaminophen per day). In people who drink
heavily or who are fasting (which also increases CYP2E1 activity), however, liver injury
may occur at doses as low as 2 to 4 grams per day. The specific drinking levels at which
acetaminophen toxicity is enhanced are still unknown. Because acetaminophen is easily
available OTC, however, labels on the packages warn people about the potentially
dangerous alcohol-acetaminophen combination. Furthermore, people should be aware
that combination cough, cold, and flu medications may contain aspirin, acetaminophen,
or ibuprofen, all of which might contribute to serious health consequences when combined
with alcohol.
 Opioids
Opioids are agents with opium-like effects (e.g., sedation, pain relief, and euphoria) that
are used as pain medications. Alcohol accentuates the opioids’ sedating effects.
Accordingly, all patients receiving narcotic prescriptions should be warned about the
drowsiness caused by these agents and the additive effects of alcohol. Overdoses of alcohol
and opioids are potentially lethal because they can reduce the cough reflex and breathing
functions; as a result, the patients are at risk of getting foods, fluids, or other objects stuck
in their airways or of being unable to breathe. Certain opioid pain medications (e.g.,
codeine, propoxyphene, and oxycodone) are manufactured as combination products
containing acetaminophen. These combinations can be particularly harmful when
combined with alcohol because they provide “hidden” doses of acetaminophen. As
described in the previous section, alcohol consumption may result in the accumulation of
toxic breakdown products of acetaminophen. Therefore, patients using opioid-
acetaminophen combination products should be cautioned about restricting the total
amount of acetaminophen they ingest daily (i.e., they should not take regular
acetaminophen in addition to the combination product).
 Warfarin
The anticoagulant warfarin is used for the prevention of blood clots in patients with
irregular heart rhythms or artificial heart valves; it is also used to treat clots that form in
extremities such as legs, arms, or sometimes the lungs. Its anticoagulant effect is acutely
altered by even small amounts of alcohol. In people taking warfarin and ingesting a few
drinks in one sitting, anticlotting effects may be stronger than necessary for medical
purposes, placing these people at risk for increased bleeding. This excessive warfarin
activity results from alcohol related inhibition of warfarin metabolism by cytochrome P450
in the liver. Conversely, in people who chronically drink alcohol, long term alcohol
consumption activates cytochrome P450 and, consequently, warfarin metabolism. As a
result, warfarin is broken down faster than normal, and higher warfarin doses are required
to achieve the desired anticoagulant effect. Thus, alcohol consumption can result in
dangerously high or insufficient warfarin activity, depending on the patient’s drinking
pattern. Therefore, patients taking warfarin generally should avoid alcohol.

36
Counseling and Guidance about Drug-Food Interactions:
The following information can be given to the patients while dispensing the
medicine.
1. Read the prescription label on the container. If you do not understand something or think
you need more information, ask your physician or pharmacist.
2. Read directions, warnings and interaction precautions printed on all medication labels
and package inserts. Even over-the-counter medications can cause problems.
3. Take medication with a full glass of water.
4. Do not stir medication into your food or take capsules apart (unless directed by your
physician). This may affect the efficacy of medication.
5. Do not take vitamin pills at the same time you take medication. Vitamins and minerals
can interact with some drugs.
6. Do not mix medication into hot drinks because the heat from the drink may destroy the
effectiveness of the drug.
7. Never take medication with alcoholic drinks.
8. Be sure to tell your physician and pharmacist about all medications you are taking, both
prescription and nonprescription.
9. Check with the pharmacist on how food can affect specific medications taken with the
food.

37
Summary of some signifiant Food-Drug Interactions
Condition Drug Use Interactions/Guidelines Examples
Allergies Antihistamine To relieve or
prevent the
symptoms of
colds, hay fever
and allergies
Food: Take with water, if GI
distress occurs consume with
food.
Exception: Fexofenadine,
bioavailability decreases if
taken with apple, orange, or
grapefruit juice
Avoid alcohol
Diphenhydramin
e
Fexofenadine
Loratadine
Cetirizine
Arthritis and
Pain
Analgesic/Antipyr
etic
To treat mild to
moderate pain
and fever
Food: For rapid relief, take on
empty stomach
Caffeine: May increase the rate
of absorption of the drug
Avoid alcohol
Acetaminophen
Non-Steroidal
Anti-Inflammatory
Drugs (NSAIDS)
To reduce, pain,
fever and
inflammation
Food: Take with food, water, or
milk to decrease stomach
upset. With a high dose of this
drug, one may need to increase
consumption of vitamin C,
vitamin K, and folate
Caffeine: Limit intake
Supplements: Limit or avoid
products that affect blood
coagulation (garlic, ginger,
gingko, ginseng, or horse
chestnut)
Avoid alcohol
Aspirin
Ibuprofen
Naproxen
Corticosteroids To relieve
inflamed areas of
the body, reduce
swelling and
itching, allergies,
rheumatoid
arthritis, and
other conditions
Food: Take with food or milk to
decrease stomach upset. Limit
grapefruit and other citrus
fruits. While taking this drug,
one may need to decrease
sodium, and supplement the
diet with calcium, vitamin D, K,
A, C, or protein
Caffeine: Limit intake
Avoid alcohol
Methyprednisol
on
Prednisone
Prednisone
Cortisone
acetate
Narcotic Analgesic To provide relief
for moderate to
severe pain
decrease stomach upset
Avoid alcohol
Codeine
combined with
acetaminophen
Morphine
Asthma Bronchodilators To treat the
symptoms of
bronchial
asthma, chronic
bronchitis, and
emphysema
Food: Take with food if
stomach upset occurs. High-fat
meals may increase the
amount of theophylline in the
body, while high-carbohydrate
meals may decrease it.
Different foods may have
decrease it. Different foods
may have varying effects
depending on the dose form
Theophylline
Albuterol
Epinephrine

38
Caffeine: Avoid eating or
drinking large amounts of
foods and beverages that
contain caffeine
Avoid alcohol
Cardio-
Vascular
Disorders
Diuretics To help eliminate
water, sodium
and chloride
from the body
Food: Take on an empty
stomach since food reduces
drug availability. Take with
food or milk if stomach upset
occurs. Since some diuretics
cause loss of potasium,
calcium, and magnesium,
supplementation of these
minerals may be necessary.
Trimterene is known as a
“potassium sparing” diuretic.
When taking triamterene avoid
eating large amounts of
potassium-rich foods such as
bananas, oranges and green
leafy vegetables or salt
substitutes. Avoid natural
licorice.
Fuorsemide
Triamterene
Hydrochlorothia
zide
Bumetamide
Metolazone
Cholesterol
Lowering
Food: Take with food. Do not
take with grapefruit or other
citrus fruits. Follow a diet low
in cholesterol and dietary fat
Avoid alcohol
Zocor
Beta Blockers To decrease the
nerve impulses
to blood vessels.
Food: Take with food to
increase bioavailability. Take
separately from orange juice,
and avoid natural licorice. It
may be necessary to decrease
dietary calcium and sodium,
which may decrease absorption
Avoid alcohol
Atenolol
Metoprolol
Propranolol
Nadolol
Nitrates To relax blood
vessels and lower
the demand for
oxygen by the
heart.
stomach with water to increase
absorption, 1 hour before
meals or 2 hours after
Avoid alcohol
Isosorbide
dinitrate
Nitroglycerin
Angiotensin
Converting
Enzyme Inhibitors
(ACEI)
To relax blood
vessels by
preventing
angiotension II a
vasoconstrictor
from being
formed.
Food: High fat meals decrease
absorption of quinapril. Ensure
adequate fluid intake. Avoid
salt, calcium, and natural
licorice.
Captopril
Enalapril
Lisinopril
Quinapril
Moexipri
HMG-CoA
Reductase
Known as
“statins”
intended to
lower
cholesterol, and
reduce the
Food: Avoid grapefruit/related
citrus with atorvastatin,
lovastatin and simvastatin.
Lovastatin should be taken with
the evening meal to enhance
absorption. Decrease dietary
Atorvastatin
Fluvastatin
Lovastatin
Pitavastatin
Simvastatin

39
production rate
of LDL
fat and cholesterol while taking
these medications
Supplements: Avoid St. John’s
wort
Avoid alcohol
Anticoagulants To prevent the
formation of
blood clots
Food: Limit foods with vitamin
K, since it produces blood-
clotting substances that reduce
the effectiveness of
anticoagulants. Do not exceed
the upper limit for vitamin E
and A
Supplements: Avoid garlic,
ginger, ginko saw palmetto,
and horse chestnut
Warfarin
Infections Antibacterials/Pen
icillin
To treat
infections caused
by bacteria and
fungi
stomach, or 1 hour before or 2
hours after food. If upset
stomach occurs, take with
food. Avoid guar gum
Supplements: Use caution
when taking vitamin K
Penicillin V
Amoxicillin
Ampicillin
Quinolones To treat
infections caused
by bacteria and
fungi
stomach occurs, take with food
but not with dairy or calcium-
fortified products alone
Caffeine: Taking these
medications with caffeine-
containing products may
increase caffeine levels, leading
to excitability and nervousness
Ciprofloxacin
Levofloxacin
Ofloxacin
Trovafloxacin
Cephalosporins To treat
infections caused
by bacteria and
fungi
stomach occurs, take with food
Cefaclor
Cefradroxil
Cefixime
Cefprozil
Cephalexin
Macrolides To treat
infections caused
by bacteria and
fungi
Food: May take with food if
stomach upset occurs
Exceptions: Zmax should be
taken on an empty stomach
one hour before or 2 hours
after food. Avoid taking with
citrus foods, citrus juices, and
carbonated drinks
Azithromycin
(Zmax)
Clarithromycin
Sulfonamides To treat
infections caused
by bacteria and
fungi
Food: Take with food and at
least 8 ounces of water
Avoid alcohol
Sulfamethoxazol
e +
trimethoprim
Tetracyclines To treat
infections caused
by bacteria and
fungi
Food: Take with food and at
least 8 ounces of water. Avoid
taking tetracycline with dairy
products, antacids, and vitamin
Tetracycline
Doxycycline
Minocycline

40
supplements containing iron
because they can interfere with
the medication’s effectiveness
Nitromidazole To treat
infections caused
by bacteria and
fungi
Food: May take with food to
decrease stomach upset, but
food decreases bioavailability
Avoid alcohol
Metronidazole
Antifungals To treat
infections caused
by fungi
Food: Take with food to
increase absorption. Do not
take itraconazole with
grapefruit or related citrus
Avoid alcohol
Fluconazole
Ketoconazole
Itraconazole
Mood
Disorders
Monoamine
Oxidase Inhibitors
(MAOI)
To treat
depression,
emotional and
anxiety disorders
Food: These medications have
many dietary restrictions and
those taking them should
follow the dietary guidelines
and physician instructions very
carefully. A rapid, potentially
fatal increase in blood pressure
can occur if foods or alcoholic
beverages containing tyramine
are consumed while taking
MAO inhibitors. Avoid foods
high in tyramine and other
pressor amines during drug use
and for 2 weeks after
discontinuation. These include
aged cheeses, aged meats, soy
sauce, tofu, fava beans,
snowpeas, auerkraut,
avocadoes, bananas, yeast
extracts, raisins, ginseng,
licorice, chocolate, and caffeine
Avoid alcohol
Phenelzine
Tranycypromine
Anti-Anxiety Drugs To treat
depression,
emotional and
anxiety disorders
Food: May take with food if
upset stomach occurs. Limit
grapefruit and citrus
consumption
Caffeine: May cause
excitability, nervousness, and
hyperactivity and lessen the
anti-anxiety effects of the
drugs
Supplements: Use caution with
sedative herbal products such
as chamomile, kava, or
stimulants such as caffeine,
guarana, or mate
Avoid alcohol
Lorazepan
Diazepam
Alprazolam
Antidepressant
Drugs
To treat
depression,
emotional and
anxiety
disorders.
Food: These medications can
be with or without food
Avoid alcohol
Paroxetine
Sertraline
Fluoxetine

41
Stimulant Food: Take with or without
meals. Limit caffeine, and
ensure adequate calcium
intake.
Methylphenidat
e
Depressant Sedative-
hypnotic
Food: Do not take with food, or
immediately after a meal
Zolpidem
Stomach Histamine
Blockers
To relieve pain,
promote healing,
and prevent
irritation from
returning
Food: These medications can
be taken with or without food,
with 8 ounces of water. A bland
diet is recommended. Take
drug 2 hours before an iron or
antacid supplement is
consumed. May decrease iron
and vitamin B12 absorption
Caffeine: Caffeine products
may irritate the stomach
Avoid alcohol
Cimetidine
Famotidine
Ranitidine
Nizatadine
Seizures Anticonvulsant/
Antiepileptic
Therapy
decrease stomach upset Avoid
grapefruit or related citrus
fruits, star fruits, or
pomegranate juice.
Supplement with calcium and
vitamin D
Avoid alcohol
Tegretol
Equetro
Carbatrol

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