Drug interactions

1. INTERACTIONS
DR. UMA TEKUR
Drug Interactions 1
DR SAHIL KUMAR
DRUG INTERACTIONS

2. OUTLINE
• Definition
• Outcomes of Drug Interactions
• Factors Contributing to Drug Interactions
• Drugs Commonly involved in Interactions
• Types of Drug Interactions
• Mechanisms of Drug Interactions
• Pharmaceutical Interactions
• Pharmacokinetic Interactions (A/D/M/E interactions)
• Pharmacodynamic interactions
• Drug-Food Interactions
• Drug-Disease Interactions
• Role of Pharmacist
• Newer Approaches to check interactions
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3. DEFINITION
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Drug Interaction is defined as the
pharmacological activity of one drug
being altered by the concomitant use
of another drug or by the presence of
some other substance.
DEFINITION

4. OUTCOMES OF DRUG INTERACTIONS
Beneficial
well-recognized interactions; do not
pose any undue risk to the patient.
• Eg Amoxicillin-Clavulanic Acid
• Eg Sulfadoxine-Pyrimethamine
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Harmful
• Unintended antagonism &
loss of therapeutic effect.
• Toxicity

5. Factors contributing to drug interactions
• Multiple diseases or predisposing illnesses.
• Multiple drug therapy.
• Multiple prescribers.
• Poor patient compliance to instructions.
• Advancing age of patient.
• Drug related factors.
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6. Drugs Commonly Involved in Interactions
• Drugs with narrow safety margin: aminoglycosides, digoxin,
lithium.
• Drugs affecting closely regulated body functions:
antihypertensives, antidiabetics, anticoagulants.
• Highly plasma protein bound drugs: NSAIDs, oral anticoagulants,
sulfonylureas.
• Drugs metabolized by saturation kinetics: phenytoin, theophylline.
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7. TYPES OF DRUG INTERACTIONS
• Drug-Drug Interaction
• Drug-Food Interaction
• Drug-Disease Interaction
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8. Mechanisms of Drug Interactions
Three mechanisms by which an interaction can occur are:
• Pharmaceutical Interaction
• Pharmacokinetic Interaction
• Pharmacodynamic interaction
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9. Pharmaceutical Interaction
• Certain drugs react with each other and get inactivated if their solutions are mixed
before administration.
• In practice, these in vitro interactions occur when injectable drugs are mixed in the
same syringe or infusion bottle.
• Diazepam + Infusion fluid----------- Precipitation
• Phenytoin + Infusion fluid-----------Precipitation
• Heparin + Hydrocortisone-------------Inactivation of heparin
• Kanamycin + Hydrocortisone-----------Inactivation of kanamycin
• Carbenicillin + Gentamicin-----------Inactivation of GentamicinDrug Interactions 9

10. Pharmacokinetic Interaction
• Involve the effect of a drug on another from the point of view that includes
absorption, distribution, metabolism and excretion.
I) ABSORPTION
INTERACTIONS
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Altered
bacterial
flora
Altered
pH
Altered
GIT
motility
Drug induced
mucosal
damage
Formation of
drug chelates
or complexes

11. A) Altered pH: Non-ionized form more lipid soluble and more readily
absorbed from GIT than ionized form.
Eg 1, Antacids Eg 2, H2 antagonists
↓pH
• Therefore, these drugs must be separated by at least 2h in the
time of administration of both.
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Decrease the tablet
dissolution
of Ketoconazole (acidic)

12. B) Complexation or chelation
Eg 1, Tetracycline interacts with iron preparations
or
Milk (Ca2+ ) Unabsorbable complex
Eg 2, Antacids (aluminum or magnesium hydroxide)
Decrease absorption of Tetracycline by 85% due to chelation.
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13. C) Drug-induced mucosal damage.
D) Altered motility
Metoclopramide (anti-emetic)
Increased toxicity of cyclosporine
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Antineoplastic agents e.g.,
cyclophosphamide
vincristine
procarbazine
Inhibit
absorption
of several
drugs
eg., digoxin
↑ absorption of cyclosporine due
to ↑ of stomach emptying time

14. E) Altered intestinal bacterial flora
In 10% of patients receiving digoxin…..40% or more of administered dose
metabolized by intestinal flora
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Broad Spectrum Antibiotics kill a large number
of the normal flora of intestine
↑ digoxin conc. and ↑ its toxicity

15. Drug Interactions 15
DISTRIBUTION INTERACTIONS
• Distribution pattern of object drug is altered.
• Major mechanism for distribution interaction is alteration in protein drug
binding.
DISPLACED DRUG DISPLACER EFFECT

16. METABOLISM INTERACTIONS
• Enzyme induction: A drug may induce the enzyme that is responsible
for the metabolism of another drug or even itself
• Eg: Rifampicin - ↓ Plasma conc. of OCPs – Contraceptive Failure.
• Enzyme inhibition: Decrease in rate of metabolism of a drug by
another. This will lead to increased conc. of target drug, leading to its
increased toxicity.
• Eg: Erythromycin - ↑ Plasma conc. of Terfenadine – Cardiotoxicity (QT).
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17. EXCRETION INTERACTIONS
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• Changes in active tubular secretion:
• Changes in Renal Blood Flow:

18. Pharmacodynamic Interaction
• Modification of the action of one drug at the target site by
another drug, independent of a change in its concentration.
• May result in synergism/additive effects/antagonism.
• SYNERGISM: When the therapeutic or toxic effects of two
drugs are greater than the sum of effects of individual drugs.
• Eg: Combination of sulfamethoxazole and trimethoprim is used
as antimicrobial agent.
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19. • ADDITIVE EFFECT: Net effect of two drugs used together
is equal to the sum of the individual drug effects.
• Eg: Combination of thiazide diuretic and beta adrenergic
blocking drug is used for the treatment of hypertension.
• ANTAGONISM: The effects of one drug can be reduced or
abolished by the presence of another drug.
• Eg: Blockade of antiparkinsonian action of levodopa by
neuroleptics and metoclopramide having anti-dopaminergic
action.
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20. Drug Food Interactions
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• GARLIC when combined with diabetes medication could cause dangerous
decrease in blood sugar level.
• Some garlic sensitive individuals may experience heart burn and flatulence.
Garlic also has anti-clotting properties (interaction with anticoagulants).
• ORANGE JUICE must not be consumed with antacids containing
aluminum. The juice increases the absorption of aluminum and leads to
severe constipation.

21. • MILK contains elements like Mg and Ca which chelate
antibiotics like tetracycline and hence decrease its absorption and
effect.
• GRAPEFRUIT JUICE inhibits CYP3A4; increasing levels of
antidepressants (sertraline), benzodiazepines, verapamil.
• VITAMIN K rich foods reduce the effectiveness of
anticoagulants (such as warfarin), increasing the risk of clotting.
• Fiber in OATMEAL and other cereals, when consumed in large
amounts, can interfere with the absorption of digoxin.
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22. • ALCOHOLIC BEVERAGES tend to increase the depressive
effect of medications such as benzodiazepines, antihistamines,
antidepressants, antipsychotics, muscle relaxants and narcotics.
• Disulfiram like reaction with metronidazole.
• Increase metabolism of warfarin and phenytoin.
• SMOKING increases activity of drug metabolizing enzymes in
the liver. Diazepam, Theophylline, Olanzapine are metabolized
rapidly and their effect is decreased.
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23. Drug Disease Interaction
• Drug – Condition interaction occurs when a drug worsens or
exacerbates an existing medical condition.
• Nasal decongestants + Hypertension… ↑ Blood Pressure
• NSAIDs + Asthmatic Patients … Airway obstruction
• Nicotine + Hypertension … ↑ Heart Rate
• Metformin + Heart failure … ↑Lactate level
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24. Role of Pharmacist
• Be vigilant in monitoring for potential drug interactions.
• Advising patients regarding proper use.
• Educate the patient on foods and beverages to avoid when taking
certain medications.
• Advising patients in disease conditions.
• Keep up-to-date on potential drug-drug and drug-food interactions
of medications to counsel the patients.
(ASHP Guidelines American Society of Health-System Pharmacists)
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25. Newer Approaches to check interactions
Free Online Drug Interaction Checking Software:
• https://www.drugs.com/drug_interactions.php (Drugs.com)
• http://reference.medscape.com/drug-interactionchecker (Medscape)
• http://www.webmd.com/interaction-checker/ (Web MD)
• http://ukhealthcare.uky.edu/Library/DrugReference/Druginteractionchecke
r/ (UK Healthcare Drug Interaction Checker)
• http://desktopindia.com/Drug-inter.aspx (Doctor’s Desktop: Medical
Practice Software - Indian)
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26. Drug Interactions
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27. Drug Interactions
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28. • Android App –
“MICROMEDEX Drug
Interactions”
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29. THANK YOU
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