2. A perspective on Drug-
Nutrient Interactions
SCOPE OF THE ISSUE
• There are so many drugs available for use in the human condition, with
continued approval of new agents, and expanded indications for existing
ones
• . Furthermore, our understanding of food components included in the
diet, whether nutrients or phytochemicals, has expanded. This makes for
an ever-widening potential for interactions between drugs and food,
food components, or specific nutrients.
• The interaction is considered significant from a clinical perspective if
the therapeutic response is altered, or nutritional status is compromised.
3. APPROACH TO DNIs
Classification
The classification of DNIs can be
approached in a variety of ways
• by drug
• by nutrient
• by patient type
• by outcome (clinical manifestations)
• by mechanism (chemical or
physiologic)
• or by location (gastrointestinal [GI]
tract, circulation, and site of effect
4. APPROACH TO DNIs
A classification system based on the location and mechanism of interaction, with both an
identified precipitating factor
The above-mentioned approach would allow DNIs to be described or examined based on
five general categories described or examined based on five general categories:
1. The impact of nutritional status on drug disposition and effect.
2. The impact of food on drug disposition and effect.
3. The impact of specific nutrients on drug disposition and effect.
4. The impact of drugs on nutritional status.
5. The impact of drugs on the disposition and effect of specific nutrients.
5. Mechanisms
• Why certain drugs and nutrients interact with each other and not with
others, relates to physicochemical factors of the medication, food or
nutrient, as well as to individual physiology whether normal or
disordered.
• At the level of the GI tract, interactions may be due to physicochemical
reactions, as well as altered enzyme or transporter function.
• Specific drugs may alter nutrient intake, absorption, storage,
metabolism, and excretion. Non-nutrient agents (herbals and other
dietary supplements) have the same potential to alter nutritional
status and nutrient disposition,
6. Impact of
Nutritional Status
and Food Intake
on Medications
• Both protein-calorie malnutrition and
obesity are known to influence drug
disposition and effect
• Several micronutrients including riboflavin
and ascorbic acid are active components in
microsomal enzyme systems used for drug
metabolism with capacity reduced in
deficiency
• Although vitamin A deficits may slow drug
metabolism in animal models, this remains
poorly defined in humans
• However, it may not even require a
clinically apparent alteration in nutritional
status for dietary changes to influence
drug response particularly when
underlying gene polymorphism plays a
role.
8. Impact of Drugs on Nutritional Status
• The impact of drugs on nutritional status or on the status of a specific
nutrient has been well recognized
• Drugs can influence nutrient absorption, distribution, metabolism, and
excretion.
• However, a few situations account for most clinically common nutrient
depletions—when a drug causes significant anorexia or malabsorption
• Even the anti-vitamin effects of a medication may be due to one or
more factors—reduced absorption or reduced conversion to active
form, interference with vitamin-dependent pathways, or increased
vitamin clearance (metabolism or excretion)
9. Continue…
• These are each more likely to occur
when used chronically, and in patients
with marginal nutritional status.
• DNIs are assumed to play negative roles
in patient outcome, but some
interactions can improve therapeutic
outcome.
• There may be as yet unrecognized
adverse nutritional effects to a given
drug. Recognized drug effects can
include a reduction in appetite or
absorption, alteration of nutrient
metabolism, and increased urinary
losses, whether used for a short or
longer duration
10. Adverse Drug
Effects Following
Nutrient Losses
• The idea that some adverse effects of
medications are directly related to their
influence on nutrient status is not new
• In other words, adverse effects of the
medication may occur through an alteration of
nutrient status. So, drug-induced nutritional
deficits may be considered as a subclass of
adverse drug effects, whether identified as
dose-related, or duration-related.
• For example, valproic acid hepatotoxicity may
be related by a common mechanism involving
drug-induced alteration in the methionine cycle
• Similarly Antiepileptic agents are likely to alter
the status of several nutrients, including folic
acid and biotin.
11. Drug
Disposition
and
Response
• Pharmakokinetics
Pharmacokinetics is important for
understanding or predicting the magnitude
or duration of an effect of a drug or
nutrient. A substance can produce an effect
only if it can reach its target(s) in adequate
concentration. Several factors can affect the
absorption and
12. Absorption
The route by which a substance is
introduced into the body affects its
pharmacokinetics
common routes of administration are listed
below
SYSTEMIC ROUTES
Systemic routes of administration are those
that deliver the substance with the intent of
producing a systemic (on the system) effect,
rather than a local effect on, for example,
the skin.
13. A subdivision of systemic route of administration is parenteral, which refers to
systemic routes other than oral, sublingual, buccal, or rectal, which are termed
alimentary routes.
Oral administration is generally the simplest, most convenient, safest (because of
slower onset of drug effect and ability to reverse a mistake), and often most
economical route of administration.
Most drugs are well absorbed from the gastrointestinal (GI) tract. The rate and extent
of absorption is a function of the physiochemical properties of the drug substance
(e.g., hydrophilic, lipophilic), its formulation (e.g., tablet, capsule, liquid,
physiological environment (e.g., stomach pH), and any metabolism in the gut wall
14. Alteration of any of these features that occurs, for example, as a result of
change in diet, lifestyle, age, or health status, can affect absorption
Nutrients and foodstuffs can affect absorption by direct binding or by
altering the physiologic environment (e.g., pH of the stomach contents).
The simple act of food ingestion, or even its anticipation, can release
digestive enzymes that inactivate certain drugs, such as penicillins.
The intravenous route of administration delivers drug substance directly
into the bloodstream.
15. The intravenous route bypasses problems of absorption from the GI
tract, allows for rapid adjustment of dose to effect, can be used even if the
patient is unconscious and avoids the “first-pass effect”
Subcutaneous administration involves the delivery of the drug into the
tissue beneath the skin for subsequent entry into the vasculature.
Intramuscular administration is generally rapid because of high
vascularity and provides an opportunity for sustained release
formulations such as oil suspensions
Inhalation provides one of the most rapid routes of drug administration
due to the large surface area and high vascularity of the lung.
16. • Other systemic routes include intraperitoneal, which is
particularly useful for the administration of drugs to small
animals
• Systemic routes of administration provide an opportunity for
drug and nutrient/food interactions at several levels,
including: the rate at which drug substance or nutrient is
available for absorption (e.g., dissolution rate, degree of
ionization, adsorption, etc.); the extent of plasma protein
binding; and the rate or route of metabolism.
17. TOPICAL
ROUTES
• Topical routes of administration—such as
direct application to the skin or mucous
membranes—for the purpose of local
action are not generally sites of
interaction between drugs and
nutrients/food.
OTHER ROUTES
Eye (ophthalmic administration)
Ear (otic administration)
Nerves (intraneural administration)
Spinal cord (e.g., epidural or intrathecal
administration)
or Brain (e.g., intracerebroventricular
administration)
do not often lead to significant
nutrient/food interactions,
18. FACTORS THAT AFFECT
ABSORPTION
The rate and extent of absorption are influenced by many factors related
both to the characteristics of the drug or nutrient substance and the
particular characteristics of the recipient at the time of administration
For example, the product formulation generally determines the rate of
dissolution under specific physiological conditions, but these conditions
depend on the person’s state of health and other factors, such as diet.
The solubility of the administered substance, its dosage, and route of
administration also affect absorption.
