Drug interaction is defined as the pharmacological activity of one drug is altered by the concomitant use of another drug or by the presence of some other substance The Drug whose Activity is effected by such an Interaction is called as a “Object drug.” The agent which precipitates such an interaction is referred as the “Precipitant”.

1. Drug interactions: Types & Mechanisms
Dr. V. S. Pawar
Associate Professor

2. After completing this module you should know:
How drug interactions are classified
The mechanisms that underlie most drug interactions
Adopt a practical approach to identifying, managing, and
monitoring interactions.
Talk to patients about drug interactions.
Learning Obectives (LOs)

3. Defination
• Drug interaction is defined as the pharmacological activity of one
drug is altered by the concomitant use of another drug or by the
presence of some other substance
• The Drug whose Activity is effected by such an Interaction is
called as a “Object drug.”
• The agent which precipitates such an interaction is referred as
the “Precipitant”.

4. Epidemiology
• In harvard medical practice study of adverse event 8%
were consider to be due to drug interaction.
• US community pharmacy study revealed 4.1 % incidence
of drug interaction in hospitalised patient.
• Australian study found that 4.4% of all ADR , which
resulted in hospital due to interaction.

5. Polypharmacy/Multi prescribers
Genetic MakeupNarrow therapeutic index drugs
Specific population/Critical illness
Factors contributing to DI

7. Mechanisms of Drug-Drug Interactions
Pharmacodynamics:
Receptor Site Interaction
Pharmacokinetic:
Interactions during ADME
Pharmaceutical:
Drug interactions before administration

8. Pharmaceutical Interactions
• Certain drugs react with each other and get inactivated if their solutions
are mixed before administration (incompatibilities )
• In practice, these in vitro interactions occur when injectable drugs are
mixed in the same syringe or infusion bottle.
• Thiopentone sodium + succinylcholine or morphine-----Precipitation
• Penicilline + Gentamycin ----------- Inactivation
• Heparin + penicillin/ gentamicin/hydrocortisone -------Inactivation
• Carbenicillin + Gentamicin-----------Inactivation of Gentamicin
• Noradrenaline + sodium bicarbonate solution-----------Inactivation

9. 1) Altered GIT absorption.
•Altered pH
•Altered bacterial flora
• formation of drug chelates or complexes
• drug induced mucosal damage
• altered GIT motility.
Pharmacokinetic Interactions

10. A) Altered pH: Non-ionized form more lipid soluble and
more readily absorbed from GIT than ionized form.
Antacids H2 antagonists
pH
• Therefore, these drugs must be separated by at least 2h in
the time of administration of both.
Decrease the tablet
dissolution
of Ketoconazole/Tetracycline
10

11. B) Altered intestinal bacterial flora
In patients receiving digoxin…..40% or more of
administered dose metabolized by intestinal flora
Broad Spectrum Antibiotics
kill the normal flora of intestine
↑ digoxin conc. and ↑ its
toxicity
Drug Interactions 11

12. c) Complexation or chelation;
EX1., Tetracycline interacts with iron preparations
or
Milk (Ca2+ ) Unabsorpable complex
Ex2., Antacid (aluminum or magnesium) hydroxide
Decrease absorption of
ciprofloxacin by 85%
due to chelation

13. D) ALTERATION IN BACTERIAL FLORA
Bacterial flora has a marked role in metabolism of some
drugs.
Long term antibiotics may kill normal flora and affect
drug absorption.
E.g. 40% or more of the administered Digoxin dose is
metabolized by the intestinal flora.
Antibiotics kills large population of Intestinal flora
thus increases the Digoxin concentration and chances of
toxicity.

14. E) ALTERATION IN GUT MOTILITY
Some drugs usually alters the GIT emptying time by
altering the peristalsis of the gut hence leading to
defected absorption
E.g. aspirin, levodopa, diazepam co-administered with
metoclopramide leads to rapid gastric emptying and
increased rate of absorption.
Same drugs with atropine leads
to delayed emptying and
decreased absorption.

15. 2) Displaced protein binding (Distribution)
Aspirin Tolbutamide
Competes for binding with
Albumin (plasma protein) Insulin release
Hypoglycemia
+

16. CYP450 most important iso-enzymes responsible for
liver metabolism.
CYP 3A4
CYP 2D6
CYP 2C8
3) Altered Metabolism

17. METABOLISM INTERACTIONS
1.ENZYNE INDUCTION
CORTICOSTEROIDS, ORAL
CONTRACEPTIVES,
COUMARINS, PHENYTOIN
BARBITURATES
DECREASED PLASMA
LEVELS; DECREASED
EFFICASY OF OBJECT DRUGS
ORAL CONTRACEPTIVES,
ORAL HYPOGLYCAEMICS
RIFAMICIN DECREASED PLASMA
LEVELS
2.ENZYME INHIBITION
TYRAMINE RICH FOOD MAO INHIBITORS
ENHANCED ABSORPTIONOF
UN METABOLISED
TYRAMINE.
COUMARINS METRANIDAZOLE
PHENYL BUTAZONE
INCREASED ANTI
COAGULANTACTIVITY.
ALCOHOL DISULPHIRAM,
METRONIDAZOLE
INCREASED IN PLASMA
ACETALDEHYDE LEVELS

18. Drug Interactions-Excretion
• Potential mechanisms exist for drug interactions at
the renal level:
 Competition at a tubular secretion site
 Competition at the tubular reabsorption site
 A change in urinary pH and/or flow

19. ACTIVE TUBULAR SECRETION
Both systems are nonselective and independent of each other
and birectional
Example- uric acid
 System for secretion of organic acids/anions:
e.g. penicillin, salicylates, glucuronides, sulphates &
endogenous substances like Uric acid.
 System for secretion of organic bases/cations;
e.g. Morphine, hexamethonium,
endogenous amines like catecholamines, choline,
histamine.

20.  Therapeutic advantages of competition:
 Probenicid inhibits active tubular secretion of
organic acids e.g. Penicillin, PAS, PAH,17-
ketosteroids: increases their plasma conc. 2 fold.
 Probenicid acts as a uricosuric agent in treatment
of gout.
 Therapeutic disadvantages of competition:
 Inhibition of nitrofurantoin secretion by probenecid
 decreased efficacy

21. Drug Interactions-Excretion

22. Pharmacodynamic Interaction
22
• 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.

23. • 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.
23

24. Drug-Food interactions
• GARLIC when combined with diabetes medication could cause
dangerous decrease in blood sugar level
• ORANGE JUICE must not be consumed with antacids containing
aluminum. The juice increases the absorption of aluminum and
leads to severe constipation
• MILK contains elements like Mg and Ca which chelate antibiotics
like tetracycline and hence decrease its absorption and effect
• VITAMIN K rich foods reduce the effectiveness of anticoagulants
(such as warfarin), increasing the risk of clotting

25. 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.
Drug
2
4

26. Online Drug Interaction Checker
http://reference.medscape.com/drug-
interactionchecker
,,,,,,,
https://online.epocrates.com/u/
1300/MultiCheck?ICID=search-DDI
,,,,,,
http://www.drugs.com/
drug_interactions.html

27. A 26 year-old female taking oral contraceptives to avoid
pregnancy also being treated with Rifampicin concomitantly.
After six months lady observed positive pregnancy test.
Why oral contraceptives failed to exhibit desired effect ?
Justify the case

28. References
•
•
•
Text book of Clinical pharmacy by Parth sarthi.
K.D.Tripathi. Essentials of Medical Pharmacology
Seventh Edition
• Principles of Pharmacology by H. L. Sharma and
K. K. Sharma
• Clinical Pharmacokinetics December 1994, Volume 27, pp
447-461
• Bonate et al; Clinical Pharmacokinetics; 1998; May 34(5)
• pp375-404

29. THANK
You