This document discusses drug interactions, including definitions, types, factors that influence interactions, and their clinical impact. It notes that drug interactions can occur when one drug affects another's absorption, distribution, metabolism, or excretion. Factors like polypharmacy, age, organ function, and genetics influence interaction risks. Interactions can decrease drug effectiveness, increase toxicity, and cause organ dysfunction. Clinicians must be aware of potential interactions to minimize harmful outcomes for patients.

2.  Drug interactions
◦ Definition
◦ Clinical relevance
◦ Types
 Factors predisposing to food-drug
interactions
 Impact of food-drug interactions

3.  Def.
 A drug interaction occurs when the
effects (activity) of one drug is
affected by the presence of another
drug, food, beverage, drink or an
environmental chemical agent.
◦ Alteration of effect of one or more
drug or the production of idiopathic
effects

4.  Identification of factors affecting the
risk of food-drug interaction
 Identification of Patients likely to be
adversely affected by a food-drug
interaction

5. 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
 Require only a single dose to affect a
permanent cure

6. Factors affecting the risk of drug interaction
 Poly pharmacy ; the more drugs a patient
takes the greater is the likelihood of a drug
interaction
 Organ functioning of a patient –particularly
the liver and the kidney
 Drug administration
 Duration of therapy
 Number of prescribers for a particular patient
and their level of coordination

7. Factors affecting the risk of drug interaction
 Patient factors
◦ Age –neonatal
 Infant
 Elderly
◦ Sex –Hormonal environment
◦ Genetic abnormalities
 E.g enzyme or receptor polymorphism
◦ Previous adverse food-drug reactions
 Allergy, atopy
◦ Presence of organ dysfunction-disease
◦ Personality and habits
 Alcohol
 Nicotine
 Adherence
 Drug-addict

8. Factors affecting the risk of drug interaction
 Prescriber factors
◦ Incorrect combinations
◦ Incorrect route
◦ Incorrect dose
◦ Incorrect duration of therapy
 Drug-factors
 Environment –sun
 Xenobiotics (e.g herbs)
 Malnutrition

9. Patients likely to be adversely affected by a drug
interaction
 The elderly or seriously ill patients
 Patients on long term therapy in chronic
disease e.g. HIV patients
 Patients undergoing complicated surgical
procedures

10. Two mechanisms of interaction
 Pharmacokinetic
 Pharmacodynamics

11.  One drug affects the process by which
the drug is absorbed, distributed,
metabolized or excreted.
There is an increase or decrease in
the amount needed to produce
pharmacological action

12.  These are interactions between drugs
which have similar or antagonistic
pharmacological effects or side effects.
 They may be due to competition at
receptor sites or occur between drugs
acting on the same physiological system.
 They are usually predictable from a
knowledge of the pharmacology of the
interacting drugs.

13.  Object drug: one whose activity is affected by
an interaction
 Precipitant drug: it precipitates the
interaction

14. Pharmacokinetic effects may be on
i) Absorption
 Complexation and adsorption

 Alteration of GI pH
 Alteration of GI micro flora- dioxins is substantially
inactivated by the GI bacteria in about 10% of individuals. A
broad spectrum antibiotic therefore ↑bioavailability.
 GI motility; altering the rate of stomach emptying affects
absorption of drugs which are absorbed in the upper part of
small intestines and can reduce absorption of e.g. levodopa by
50%
◦ Slows (e.g. atropine, opiates)
◦ Accelerates (e.g. Metoclopramide)

15.  Absorption by fatty, high protein and fiber
diets
◦ Chelation
◦ Gastric acid secretion
◦ Alter gastric pH
◦ Alter gatric intestinal motility
◦ Affect transport proteins e.g. p-glycoproteins

16. ii) Distribution
 Displacement: On protein binding – relative
affinities for plasma proteins.
One drug can displace another there by
increasing its proportion to diffuse form for
plasma to its site of action.
NOTE: The less bound a drug is, the more
efficiently it can traverse cell membranes or
diffuse.

17.  Protein binding
 Most drugs possess physicochemical
affinity for plasma proteins and get
reversibly bound to these.
 Acidic drugs generally bind to plasma
albumin and basic drugs to α1 acid
glycoprotein

18. iii) Metabolism
 Many drugs are metabolized in the liver.
 Induction of the hepatic microsomal enzyme by
one drug can gradually increase the metabolism
of another.
 Inhibition of the hepatic microsomal enzyme by
one drug can gradually decrease the metabolism
of another.
 Although there is an overlap ach CYP isoenzyme
tends to metabolize a discrete range of
substances.
 The genes for isoenzymes vary between
individual and, sometimes ethnic groups which
may affect metabolism of drugs.

19. iv) Renal excretion
 Changes in the active tubular secretions
 Alteration in urinary PH
 Blood flow alteration
 Competition occurs between drugs which
share active transport mechanisms in the
proximal tubule. E.g. Salicylates and some
other NSAIDS delay the excretion of
methotrexate lading to serious methotrexate
toxicity.

20.  Pharmacodynamics effects may be;
Agonism/antagonism
Addition /summation
Synergism/potentiation

22.  Grapefruit is the most well-known example,
but also sevillian orange, pomelo and star
fruit contain agents that inhibit cytochrome
P450 3A4 (CYP3A4)
 Furanocoumarins inhibit the intestinal CYP
3A4 and increase the oral bioavailability
Felodipine, midazolam, cyclosporine and
raise their concentrations above toxic levels

23.  Grape fruit juice P-gp activity modifying the
disposition of drugs that are P-gp substrates
such as talinolol
 Cholesterol-lowering agent lovastatin -
taken with food to enhance gastrointestinal
absorption and bioavailability.
 The absorption of rosuvastatin -administered
on an empty stomach

24.  Some vegetables (broccoli, Brussels sprouts,
kale, parsley, spinach, and others) are high in
vitamin K.
 Eating large quantities or making sudden
changes in the amounts eaten of these
vegetables, interferes with the effectiveness
and safety of warfarin therapy

25.  Interaction with tyramine-containing food
(matured cheese, red vine, ripped bananas,
yogurt, shrimp paste and salami) or so called
cheese reaction, since they are capable of
producing hypertensive crisis in patients
taking MAOIs

26.  The absorption of ACEs inhibitors is
increased when taken on an empty stomach
 Concomitant moderate sodium restricted
diets

27.  Avoid co-administration of antibiotics with
milk products which are rich sources of
divalent ions, such as calcium and
magnesium that complex with some
antibiotics and prevent their absorption
 Casein and calcium present in milk decrease
the absorption of ciprofloxacin
 Azithromycin absorption is decreased when
taken with food, resulting in a 43% reduction
in bioavailability

28.  Tetracycline should be taken one hour before
or two hours after meals, and not taken with
milk because it binds calcium and iron,
forming insoluble chelates, and influencing
its bioavailability
 Enteric-coated tablets that start to
disintegrate when they reach the middle-to
lower region of the small intestine could
reduce negative food effects

29.  For rapid relief, acetaminophen should be
taken in an empty stomach because food may
slow the body absorption of acetaminophen
 NSAIDs like ibuprofen, naproxen, ketoprofen
and others can cause stomach irritation and
thus they should be taken with food or milk.

30.  Bronchodilators like theophylline, albuterol, and
epinephrine possess different effects with food.
 Avoid alcohol if taking theophylline medications
because it can increase the risk of side effects
such as nausea, vomiting, headache and
irritability.
 Avoid eating or drinking large amounts of foods
and beverages that contain caffeine (e.g.,
chocolate, colas, coffee, and tea) since
theophylline is a xanthine derivative and these
substances also contain xanthine.

31.  Glimepiride is an antidiabetic and a new
generation sulfonylurea derivative should be
administered with breakfast or the first main
meal of the day
 The maximum effectiveness of acarbose, an
alpha-glucosidase inhibitor is attained when
the drug is taken immediately at the start of
each meal (not half an hour before or after),
because it delays the carbohydrate
absorption by inhibiting the enzyme alpha-
glucosidase.

32. Factors predisposing to drug interactions

33.  Polypharmacy; the more drugs a patient takes
the greater is the likelihood of a drug
interaction
 Narrow TW requiring careful dose control
 Drug either an inducer or inhibitor of liver
enzymes
 Use for a long period of time
 Drugs which exhibit zero-order kinetics

34.  Multiple drug therapy
 Severe illness
 Organ functioning of a patient –particularly the
liver and the kidney. Pts with impaired
renal/hepatic function
 Age; elderly and young
 Co-morbid patients
 Genetics

35.  Loss of therapeutic effect of one or
all drugs
 Increased pharmacological activity of
one
 Increased toxicity of one drug
 Organ dysfunction / failure

36.  Practitioners should be continually alert to the
possibility of drug interactions and take
appropriate steps to minimize their
occurrence.
 Incase the combination of potentially
interacting drugs is unavoidable, the dose of
the drug likely to have increased effects as a
result of the interaction should be reduced
 Management of the side effects of interaction
 Avoid concomitant administration
 Individualize patients therapy

37.  Patients education
 Always ask for non prescription medicines
 Modify dose of one of the interacting drug
 Patient taking a combination of potentially
interacting drugs should be monitored for
toxic effects using clinical variables or
plasma drug levels for at least 2 weeks or
until they are stable
 It may be appropriate to switch one of the
treatment to one which doesn’t interact.

38.  Undesirable drug interactions can be
prevented.
 Becoming more familiar with potential drug
interactions can help clinicians predict and
explain a patient’s response to medications