DRUG INTERACTION

DEFINITION
A drug interaction is a situation in which a substance
affects the activity of a drug.
Drug : that is the active chemical substance.
Medicine which is a particular preparation containing the
drug.
The effects are increased or decreased, or they produce a
new effect that neither produces on its own.
Interaction between drugs (drug-drug interaction).
Interactions between drugs & foods (drug-food interactions),
as well as drugs & herbs (drug-herb interactions).
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 Do not take alcohol while undergoing treatment with this

medicine unless otherwise advised by your doctor or
pharmacist
* Antidiabetic agents
* Cimetidine
* Disulfiram
* Griseofulvin
* Metronidazole
* Phenytoin
* Procarbazine (Antineoplastic )
* Tinidazole
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 Do not take alcohol while undergoing treatment with this

medicine unless otherwise advised by your doctor or
pharmacist
* Antidiabetic agents
* Cimetidine
* Disulfiram
* Griseofulvin
* Metronidazole
* Phenytoin
* Procarbazine (Antineoplastic )
* Tinidazole
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Reducing risk of interactions

Identify risk factors
Take a thorough drug history
Know your drugs
Have reliable references
Consider therapeutic alternative
Avoid complex regimens
Educate patient/ prescriber
Monitor therapy
Individualize therapy
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Types of drug interaction

Drug food interactions

Drug drug interactions
Drug disease interactions
Drug environmental chemicals interactions
Drug laboratory tests interactions

Drug food interactions

A drug-food interaction happens when the food, eat or drink affects the
ingredients in a medicine so the medicine can't work the way it should.
Drug-food interactions can happen with both prescription and over-thecounter medicines, including antacids, vitamins and iron pills.
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 When drugs and certain foods are taken at the same time
they can interact in ways that diminish the effectiveness
of the ingested drug or reduce the absorption of food
nutrients.
Additionally, vitamin and herbal supplements taken with
prescribed medication can result in adverse reactions.

How foods and drugs can interact

Food can speed up or slow down the action of a medication.
Impaired absorption of vitamins and minerals in the body.
Stimulation or suppression of the appetite.
Drugs may alter how nutrients are used in the body.
Herbs may interact with anesthesia, beta-blockers, and anticoagulants.

Factors Affecting Foods - Drugs Interaction

The dosage of the drug.
A person's age,
A person's size (SA)
A person's state of health.
When the food is eaten and when the medication is taken.

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Are all medicines affected by food?

Not, all medicines are not affected by food, but many medicines can be
affected by what you eat and when you eat it.
For example, taking some medicines at the same time that you eat may
interfere with the way your stomach and intestines absorb the medicine.
The food may delay or decrease the absorption of the drug.
This is why some medicines should be taken on an empty stomach (1 hour
before eating or 2 hours after eating).
Some medicines are easier to tolerate when taken with food.
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Facts about drug-food interactions

* Read the prescription label on the container. If you don't understand
something, ask your doctor or pharmacist about it.
* Read all directions, warnings and interaction precautions printed on
medicine labels and packages. Even over-the-counter medicines can
cause problems.
* Take medicine with a full glass of water, unless your doctor tells you
differently.
* Don't stir medicine into your food or take capsules apart (unless your
doctor tells you to) because this may change the way the drug works.
* Don't take vitamin pills at the same time you take medicine because
vitamins and minerals can cause problems if taken with some drugs.
* Don't mix medicine into hot drinks because the heat may keep the drug
from working.
* Never take medicine with alcoholic drinks.
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Medications which should be taken

on an EMPTY stomach
Omeprazole
Roxithromycin
Lansoprazole
Captopril
Flucloxacillin.
Penicillamine.
Levothyroxine (thyroxine).
Penicillin V (phenoxymethylpenicillin).
Oxytetracycline.
Rifampicin.
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Medications which should be

Taken with FOOD

ACE-Inhibitors (Blood pressure medication class)

Diuretics
Erythromycins (Antibiotics), Take with food if it upsets your stomach
Glipizide (Diabetes Drug class),
Glyburide (Diabetes Drug class), Avoid alcohol.
Metformin (Diabetes Drug class),
NSAIDs (For Pain), such as ASPIRIN,Take with food or milk
Quinolones (Antibiotics), such as CIPRO, Drink plenty of fluids. Do not take with
antacids or iron supplements
Statins (For Cholesterol), such as atorva. Take with evening meal. Follow low
cholesterol diet
Warfarin (Blood thinner), such as COUMARIN
Bisphosphonates (For Osteoporosis)
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Drug drug interactions

A drug-drug interaction occurs when the effect of one drug is
altered by the presence of another drug in the body.
For example:
One drug might reduce or increase the effects of another drug.
Two drugs taken together may produce a new and dangerous interaction.
Two similar drugs taken together may produce an effect that is greater
than would be expected from taking just one drug.
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Example
Mixing antidiabetic medication (e.g., oral hypoglycemics) and beta
blockers can result the decreased response of the antidiabetic drug and
increased frequency and severity of low blood sugar episodes.
Mixing antidiarrheal medication and tranquilizers, sedatives, or
sleeping pills can result in an increased effect of tranquilizers, sedatives,
or sleeping pills.
Mixing antihypertensive medication (e.g., Reserpine) and digitalis can
result in abnormal heart rhythms.

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 Mixing anticoagulants (e.g.Warfarin) and sleeping pills can result in

decreased effectiveness of the anticoagulant medication.
In addition to prescription medications, over-the-counter medications
can interact with each other. Some examples include:
Taking a cough medication with alcohol at the same time as an
antihistamine medication can increase drowsiness and decrease alertness.
Mineral oil taken with fat-soluble vitamins (A, D, E, K) can decrease the
absorption of the vitamins.

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 Aspirin can significantly increase the effect of blood thinning drugs

(anticoagulants), thus increasing the risk of excessive bleeding.
Antacids can cause blood-thinning drugs (anticoagulants) to be absorbed
too slowly.
Antacids can interfere with drug absorption of antibiotics (i.e. tetracycline),
thereby reducing the effectiveness of the drug in fighting infection.
Antihistamines, often used for allergies and colds, can increase the sedative
effects of barbiturates, tranquilizers, and some prescription pain relievers.

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 Decongestants in cold and cough medications can interact with diuretics or

"water" pills to aggravate high blood pressure.
Iron supplements taken with antibiotics can reduce or stop the ability of the
antibiotics to fight infection.
Salt substitutes can interact with "water" pills or blood pressure medication
to increase blood potassium levels. This can result in symptoms of nausea,
vomiting, muscle cramps, diarrhea, muscle weakness, and cardiac arrest.
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Mechanisms of Drug Interaction

1. Pharmacokinetic Drug Interactions
2. Pharmacodynamic Drug Interactions

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Pharmacokinetic Drug Interactions

Inhibition of Absorption
Enzyme Inhibition Increasing Risk of Toxicity
Enzyme Inhibitors Resulting in Reduced Drug Effect
Enzyme Induction Resulting in Reduced Drug Effect
Enzyme Induction Resulting in Toxic Metabolites
Altered Renal Elimination

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Pharmacokinetic vs.
Pharmacodynamic interactions
Me
Pharmacokinetic: Amount of drug in blood is altered

Pharmacodynamic: Amount of drug in blood remains the

same, but its effect is altered
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ADME
Absorption
Distribution
Metabolism
Excretion
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CLASSIFICATION OF MECHANISM
Alterations in absorption
Alterations in hepatic metabolism
Alterations in renal clearance
Alterations in plasma protein binding

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1. ALTERATIONS IN ABSORPTION
a. Complexation / Chelation
Example: antacids + tetracycline

Impact: tetracycline complexes with divalent cations

forming an insoluble complex

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b. Altered GI Transit
Example: anticholinergics + acetaminophen
Impact: delay in absorption of acetaminophen

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c. Altered Gastric pH
Example: H-2 blockers + ketoconazole
Impact: dissolution of ketoconazole is decreased,
resulting in reduced absorption

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2. ALTERATIONS IN HEPATIC METABOLISM

a. Induction of Metabolism
Example: phenobarbital + warfarin
Impact: phenobarbital increases the metabolism of
warfarin, resulting in reduced anticoagulation

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b. Inhibition of Metabolism

Example: cimetidine + theophylline

Impact: cimetidine reduces the clearance of theophylline
causing an increase in adverse effects

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3. ALTERATIONS IN RENAL CLEARANCE

a. Increase in Renal Blood Flow
Example: hydralazine + digoxin
Impact: hydralazine increases the renal clearance of
digoxin

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b. Inhibition of Active Tubular Secretion

Example: probenecid (antigout)+ penicillin

Impact: probenecid prolongs the half-life of penicillin,
allowing single dose therapy

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c. Alterations in Tubular Reabsorption

Example: antacids + aspirin
Impact: antacids reduce the tubular reabsorption
of salicylate via an increase in urine pH

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4. ALTERATIONS IN PLASMA PROTEIN

BINDING
Example: phenytoin + valproic acid
Impact: protein binding of valproic acid is reduced and
total Css decreased

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Absorption based interactions

One drug make the absorption of another drug
Faster or slower
Less or more complete

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Mechanisms
pH

Gastric emptying and intestinal motility

Physico-chemical interaction

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Changes in pH of G.I.T.
contents
Stomach
pH is variable.
Antacids pH
Alcohol and some foods cause acid secretion pH
Small and large intestine.
pH always near neutral.
No significant changes seen.
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 Most drug absorption occurs from the intestine, not the stomach
(Surface area). Changes in rate of absorption from the stomach are of
little consequence.
Acidity also changes the rate of dissolution of acid drugs. Antacids
make them dissolve quicker which cancels out (or even) exceeds the
effect of ionisation changes.

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Pharmacodynamic Drug Interactions

Additive Pharmacodynamic Effects
Antagonistic Pharmacodynamic Effects

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Adverse drug reactions

as defined by WHO:
Any response to a drug which is noxious and unintended and
which occurs at doses used in man for prophylaxis, diagnosis or
therapy.
An ADR is any unwanted effect resulting from a drugs use in
treatment.

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ADR may result from:

Effects of the drug
Illness (physiological condition of the patient)
Interaction with each other
ADR may be:
Are undesirable
Are unintentional
Are suspected (not necessarily proven)
May develop as a consequence of therapy or other procedure

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Not always the active ingredient causing the problem but may also
be due to:
Solvent
Excipients
Formulation
Contaminants produced in the manufacturing process.

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Causes of ADR
Pharmacokinetic causes
Pharmacodynamic causes
Patient-related factors
Drug-related factors

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 Pharmacokinetic causes
The way the drug is handled by the body during ADME may
affect humans in an adverse manner
Example:
diazepam in patients with liver failure prolonged coma;
ototoxicity with aminoglycosides when used in patients with
renal failure
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 Pharmacodynamic causes
Increased sensitivity of target organs in the body to drugs

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 Patient-related factors
presence of renal, hepatic and cardiac disease
age
previous ADR or drug allergy
sex
genetic influence
miscellaneous (diet, smoking, alcohol, environmental exposures)

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 Drug-related factors
pharmaceutical properties
pharmacokinetic properties
pharmacodynamic properties

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6 types of ADR
Type A (Augmented)
Type B (Bizzare)
Type C (Continuous)
Type D (Delayed)
Type E (Ending Use)
Type F (Failure of Efficacy)
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 Type A or Augmented
refers to actions related to the pharmacological activity of a
drug
Extension effects predictable, dose related responses arising from

an extension therapeutic effect.

Example:

Benzodiazepine (anxiety neurosis) sedation and falls trauma

Furosemide (diuresis) water and electrolyte imbalance

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 Adverse effect - predictable, dose-dependent reactions

unrelated to the goal of therapy
Examples:
Atropine dryness of mouth
Captopril cough
Codeine constipation
Nitroglycerin headache
Propranolol bronchial asthma

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 Type B reactions or Bizzare

refers to totally abnormal effects, unrelated from the
drugs known pharmacological actions

Idiosyncrasy is an example of bizzare reaction:

Genetically abnormal response
Dose-dependent
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Characteristics of Bizzare Reactions:

no formal dose-response curve and very small doses of the drug may elicit the
reaction once allergy or idiosyncrasy is established
reactions disappears on discontinuation of the drug
illness is often recognizable as an immunological reaction
undetectable during conventional testing
little or no relation to the usual pharmacological effects of the drug
delay between first exposure to the drug and the occurrence of the subsequent
adverse reaction

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Genetic
Abnormality

Drugs

Idiosyncratic
Response

Abnormal
hemoglobin

Phenacitin,
Sulfanilamides

Methemoglobinemia
Hemolytic anemia

Erythrocyte G6PDdeficiency

Aspirin
Sulfonamides
Vitamin C

Hemolytic anemia

Low plasma ChE

activity

Procaine

Local anesthetic
toxicity

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 Type C Reactions or Continuous

Long term effects are usually related to the dose and
duration of treatment.
Example:
Ethambutol optical neuropathy

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 Type D reactions or delayed

Carcinogenesis
Hormonal
Gene toxicity
Suppression of immune response
Adverse Effects associated with reproduction
teratogens

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 Type E Reactions or Ending of Use (Withdrawal

Syndrome)
Alcohol delirium tremens
Barbiturates restlessness, mental confusion, convulsion
Clonidine rebound hypertension
Opioids narcotic withdrawal
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 Type F Reactions or Failure of Efficacy

can be attributed to lack of efficacy of drug products
Examples:
Failure to control infection (microbial resistance)
Uncontrolled hypertension
Intractable pain

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Overall Drug Risk

Red (High Risk)
Orange (Elevated Risk)
Yellow (Guarded Risk)
Blue (General Risk)
Green (Low Risk)

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Questions.
Define drug interaction. What are the types of drug interaction explain with
suitable example?
Write a note on:
Drug drug interaction,
Drug food interaction.

Define ADR. What are the types of ADR.

Write a note on ADR.
Write a note on predictable & non-predictable adverse reactions.

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