Drug Interactions:

Basic Concepts
NUTD-11805, 8th Semester,
By
Ms. Rabia Khokhar
Ph.D. (Scholar), M.Phil., R.Ph.
• Drug–drug interaction: alteration of the effect of one drug caused by the
presence of a second drug.
• Drug–nutrient interactions: alteration of the effect of a drug or nutrient caused
by the presence of a second agent.
• Drug interactions can be beneficial or detrimental.
• At times we intentionally produce a drug–drug interaction.
• Administration of drug product like carbidopa/levodopa (Sinemet®). Levodopa is converted
to dopamine in the central nervous system (CNS), thereby exerting an effect against
symptoms of Parkinson’s disease. Carbidopa acts as a chemical decoy, which binds to the
enzyme that converts levodopa to domapine outside the CNS. This increases dopamine levels
in the CNS while limiting side effects of increased dopamine in peripheral tissues. In
combination, the paired drugs produce additive effects.
• Patients with numerous disease states may require treatment with interacting
drugs. Where these interactions cannot be avoided, this fact is taken into account
when planning therapy.
• Many times dosing is not altered at all, but usual monitoring is increased
Types of Drug–Drug and
Drug–Nutrient Interactions
The types of interactions that can occur include:
1. Potentiation,
2. Inhibition,
3. Alteration of absorption,
4. Direct chemical interaction,
5. Alteration of metabolism,
6. Alteration of distribution,
7. Competition at the site of action, and
8. Alteration of elimination
Potentiation
• can be additive or synergistic and refers to an increase in the effect of
one drug as a result of a second drug or nutrient.
EXAMPLE
➢The increased pain relief experienced when acetaminophen is
combined with a narcotic (Tylenol #3®, Vicodin®, Lortabs®) illustrates
a positive example of this effect.
➢Adding bananas, potatoes, and other foods rich in potassium to the
diet at the same time a patient is taking a prescribed potassium
supplement (e.g., Kaon-Cl®) would cause an additive food–nutrient
effect with a therapeutic purpose.
Inhibition
• refers to the decrease of effect when two substances have opposite effects on a
process.
EXAMPLE
➢The decreased anticoagulant effect of warfarin (Coumadin®) seen when vitamin K
intake is increased is a negative example of this type of interaction.
➢Warfarin therapy frequently requires adjustment because of such inhibition,
especially when patients suddenly increase their intake of green leafy vegetables
rich in vitamin K. (blood clot formation- thrombosis which may lead to
thromboembolism)
➢This is a real hazard for patients who are avid gardeners and whose vitamin K
intake can vary drastically from season to season.
➢Caffeine, a nonnutritive food constituent, may oppose the pharmacological effect
of tranquilizers
Alteration of absorption
• EXAMPLE: Decreased absorption of iron from food is seen when
antacids are taken on a chronic basis with iron-containing foods. This
may result in iron deficiency anemia with its characteristic microcytic,
hypochromic, red blood cells.
• EXAMPLE: Grapefruit juice will increase the bioavailability of
cyclosporine (Sandimmune®). This will decrease the potential for
organ rejection by recipients of organ transplants, but may also
increase the potential for cyclosporine toxicity.
• NOTE: Deliberate ingestion of grapefruit to decrease cytosporine
doses is not advised due to the unpredictable nature of this
interaction.
Direct chemical interaction
• EXAMPLE: reaction between dextrose and amino acids in parenteral
nutrition.
• This is the same reaction seen when meats are cooked and is known
as the Maillard reaction.
• The substrates involved tend to reduce sugars and amino acids, and
these factors limit the storage time for parenteral nutrition solutions.
The reaction results in a darkening of the solution
Alterations of metabolism
• This generally occurs in the liver but may also be peripheral.
• Many enzymes responsible for drug metabolism are part of the
cytochrome P-450 family.
• EXAMPLE: St. John’s Wort induces an increase in the activity of one P-
450 isoform termed CYP 3A4. This can result in decreased levels of
cyclosporine, indinavir, and oral contraceptives.
• This drug interaction with St. John’s Wort demonstrates the potential
for herbal products to participate in significant herb-drug interactions
when used in combinations with conventional medications.
Alterations of distribution
• Alterations of distribution may occur when drugs are protein-bound. Binding to protein
will generally reduce the amount of free drug. Decreased amounts of free drug may
decrease the activity of the drug and also decrease the metabolism and elimination of
the drug.
• In this type of interaction, one substance that is bound displaces another bound
substance from a binding site. The effect, if any, may be transient because the increased
effect of the free drug may be countered by increased metabolism and excretion of the
free drug. Some significance is possible if the second agent is taken on an intermittent
basis.
EXAMPLE:
• Diazepam (Sedative/ muscle relaxant) displaces Phenytoin (anticonvulsant) from plasma
proteins, resulting in an increased plasma concentration of free phenytoin and an
increased risk of toxicity. Phenytoin (aka Dilantin) has a narrow therapeutic index and the
relationship between dose and plasma concentration is non-linear. Small dosage
increases in some patients may produce large rises in plasma concentrations with acute
and toxic side effects
Competition at the site of action
EXAMPLE: Effect of naloxone (Narcan®) on narcotics.
• Naloxone (opioid antagonist) reverses the effects of narcotics (opioids) at a
receptor site. This can be useful after surgery to reverse the effects of
intraoperative narcotics.
• Naloxone is also useful in the treatment of narcotic overdoses. Caution is
needed if an individual is dependent on narcotic drugs because naloxone
can cause withdrawal symptoms.
• CAUTION! This interaction is further modified by drug metabolism.
Naloxone is eliminated faster than the narcotics that it affects. It is,
therefore, necessary to monitor a patient who has received a narcotic
overdose even after he appears to have recovered. The naloxone may wear
off, and then the narcotic effect will recur.
Alteration in elimination
• Renal excretion may also be involved in interactions between drugs
and nutrients.
• EXAMPLE: Effect of most diuretics (e.g., loop diuretics and thiazide
diuretics) on potassium.
➢These diuretics result in increased loss of potassium in the urine.
➢Remedy: may require pharmacological or nutritional supplementation of
potassium intake.