This document discusses drug-drug interactions, including their definition, types, mechanisms, and consequences. It defines a drug-drug interaction as occurring when one drug affects the pharmacological activity of another drug taken at the same time. The main types of interactions are due to drugs interacting at the absorption, distribution, metabolism, and excretion levels. Mechanisms include pharmaceutical, pharmacokinetic, and pharmacodynamic effects. Consequences range from decreasing or increasing drug effects to serious adverse reactions like organ damage. Factors that increase interaction risk and ways to reduce risk are also outlined.

1. DRUG-DRUG INTERACTION
Muskan Arora
M.Sc.
Clinical research,

2. Contents
1. Definition
2. Types of drug interaction.
3. Consequences of drug-drug interaction.
4. Factors affecting drug interaction.
5. Mechanism of drug interactions.
• Pharmaceutical interactions
• Pharmacokinetic interactions
• Pharmacodynamics Interactions
6. Ultimate consequences of drug interaction.
7. Reducing the risk of drug interactions.

3. DEFINITION
 Drug-drug interactions occur when the
pharmacological activity of a drug is altered by the
concomitant use of another drug or by the presence of
some other substances.
 The drug whose activity is affected by such an
interaction is called the object drug and the agent
which precipitates such an interaction is referred to as
the precipitant.

4. • Types of drug interaction:
1. Drug-drug interaction
2. Food-drug interaction- Example: inhibition of
metabolism of several drugs(cardio-vascular drugs)
by grapefruit juice.
3. Chemical-drug interaction- Example: interaction of
drug with alcohol, tobacco etc.
4. Drug-laboratories test interactions- Alteration of
diagnostic laboratory test result in the presence of a
drug. Such as Levodopa and uric acid.
5. Drug-disease interactions- worsening of disease in
presence of a drug.

5. Consequences of drug-drug interaction:
A drug-drug interaction can delay, decrease, or
enhance absorption of either drug. This can decrease
or increase the action of either or both drugs or
cause adverse effects.

6. • Decreased effect – Tetracyclin taken with calcium
causes the Ca ions in the stomach to bind with the
antibiotic thus decreasing its absorption .
• Increased effect – pennicillin administered with
probenecid to reduce uric acid content thus
preventing gout.

7. • Some serious adverse drug reactions:
ADVERSE DRUG
REACTION
TYPE OF DRUG EXAMPLE
Anaemia (resulting from
decreased production or
increased destruction of
red blood cells)
Certain antibiotics Chloramphenicol
Liver damage Antibiotics
Iron supplements (in
excessive amounts)
Tetracyclin
-
Stomach or intestinal
ulcers
Anticoagulants Heparin
Warfarin
Kidney damage Antibiotics Gentamicin

8. FACTORS EFFECTING DRUG INTERACTION
1.Multiple drug therapy-
• Therapy in patients suffering from hypertension and
congestive heart failures includes anti-hypertensives
as well as digitalis that may lead to abnormal heart
rhythms.
• Concurrent use of non-prescription drugs, for eg;
aspirin along with herbal medications can lead to
drug interaction.
• Theoretically, there is 50% possibility for a drug
interaction to occur if patient is receiving 5
medications and 100% for 7 medications.

9. 2.Multiple prescribers
One doctor may prescribe an anxiolytic to the patient
while other may prescribe antihistamine having
sedative properties that may cause excessive
depressant effect.
3.Multiple pharmacological effect of drug:
Most drugs exhibit more than one type of
pharmacological action and have the capacity to
influence many physiological systems. Hence, two
concomitantly used drugs may affect same system.
Eg: antihistamines enhance the sedative effect of
tranquillizers

10. 4.Multiple diseases:Some patients take several drugs
owing to their suffering from more than one disease,
eg; patient with both diabetes and hypertension. In
this oral glyceamics and beta blockers can result in
decreased response to drugs resulting in elevated
blood sugar levels.
5. Poor patient compliance: This occurs when patient
does not take medications as intended by the doctor
that may lead to under-dosing thus a consequent
drug interaction.
6. Advancing age of patients: increased drug
interactions in elderly is mainly due to decreased
liver function.

11. Mechanism of drug interactions:
• Three main mechanisms by which interaction can
develop are:
1. Pharmaceutical interactions
2. Pharmaco-kinetic interactions
3. Pharmaco-dynamic interactions

12. Pharmaceutical interactions
Also called as incompatibility, a physicochemical
interaction that occurs when drugs are mixed i.v
infusions causing inactivation or precipitation.
Example:Ampicillin interacts with dextran in solutions
further broken down to form chemical complexes.

13. Pharmacokinetic interaction
• These interactions are those in which the ADME
properties of an object drug is altered by the precipitant
hence known as ADME interactions.
• The resultant effect is altered plasma concentration of
the object drug.
• These can be classified as:
1.Absorption interaction
2.Distribution interaction
3.Metabolism interaction
4.Excretion or elimination interaction

14. A FLOWCHART OF MECHANISM:

15. Absorption interaction
• These are those where the absorption of the
object drug is altered.
• The net effect of such an interaction is;
a) Faster or slower drug absorption
b) More or less drug absorption

16. • Some important pharmacokinetic interaction
Object Drug Precipitant drug Influence on object drug
Absorption interactions
1. Complexation and Absorption
Tertracyclin like
cioprofloxacin
Antacids, food, mineral
supplements containing Al,
Mg, Fe, Zn, Bi and Ca ions.
Formation of poorly
soluble and unabsorbable
complex with such heavy
metal ions.
2. Alteration of GI pH
Sulphonamides, aspirin
Ferrous sulphate
Antacids
Sodium bicarbonate
Calcium carbonate
Enhance dissolution and
absorption rate
Decreased dissolution and
absorption rate.
3. Alteration Of Gut Motility
Aspirin, paracetamol,
levodopa
Levodopa, lithium
carbonate
Metoclopramide
Anticholinergics
Increased rate of
absorption.
Decreased.

17. Object drug Precipitant drug Influence on object drug
4. Alteration of GI Microflora
Digoxin Antibiotics Increased bioavailability
due to destruction of
bacterial flora.
5. Mal absorption syndrome
Vitamin A, B12, digoxin Neomycin and colchicines Inhibition of absorption
caused by neomycin

18. Distribution interaction
• Interaction where the distribution pattern of
the object drug is altered.
• Major mechanism is the alteration in protein-
drug binding.
Competitive displacement interaction
Displaced drug Displacer Influence
1.Anti-coagulants
(Warfarin)
2. Tolbutamide
Phenylbutazone,
salicylates
Sulphonamides
Increased clotting time,
hence increased risk of
haemorrhage.
Increased hypo-glycemic
effect.

19. Metabolism Interaction
Interaction where the metabolism of the object drug is
altered. By two ways:
1.Enzyme induction: increased rate of metabolism.
2.Enzyme inhibition: decreased rate of metabolism.
1.ENZYME INDUCTION
OBJECT DRUG PRECIPITANT DRUG INFLUENCE
1.Corticosteroid, oral
contraceptives,
phenytoin
2.Oral contraceptives,
hypoglyceamics,
coumarins.
Barbiturates
Rifampicin
Decreased plasma
level. Decreased
efficacy of object drug.
Decreased plasma
levels.

20. OBJECT DRUG PRECIPITANT DRUG INFLUENCE
ENZYME INHIBITION
1. Tyramine rich food.
2. Alcohol
MAO Inhibitors
Disulphiram,
metronidazole,trinidazol.
Enhanced absorption of
unmetabolised tyramine.
Increased plasma
aldehyde level.

21. EXCRETION INTERACTIONS
• Interaction that result in change of the excretion
pattern of the drug.
• Major mechanism of action:
1) Alteration in renal blood flow
2) Alteration of urine pH
3) Competition for active secretion
4) Forced diuresis

22. EXCRETION INTERACTION
OBJECT DRUG PRECIPITANT DRUG INFLUENCE
1.CHANGES IN ACTIVE TUBULAR SECRETION
a) Penicillin,
cephalosporin, nalidixic
acid.
b) Acetohexamide
Probinicid.
Phenylbutazone
Elevated plasma level of
acidic drugs; risk of toxic
reactions.
Increased hypoglycaemic
effect.
2.CHANGES IN URINE pH
Aphetamine, tetracycline,
quinidine
Antacids, thiazides,
acetazolamide
Increased passive
reabsorption of basic
drugs;
Increased risk of toxicity.
3.CHANGES IN RENAL BLOOD FLOW
Lithium bicarbonate NSAIDs Decreased renal clearance
of lithium; risk of toxicity.

23. PHARMACODYNAMICS INTERACTIONS
• Interactions in which the activity of the object drug
at its site of action is altered by the precipitant.
• These may be:
1.Direct pharmacodynamic interactions.
2. In-direct pharmacodynamic interactions.

24. i) Direct pharmacodynamic interactions- Interactions
where drugs having similar or opposing
pharmacological effects are used concurrently. This
leads to;
a) Antagonism: Drugs having opposing action.
Example: Acetylcholine and Nor-adrenaline have
opposing effects on heart.
b) Addition or summation: Drugs have similar actions
and the resultant effect is the sum of individual
drug responses.
Example: CNS depressants like sedatives, hypnotics,
etc.

25. c)Synergism or Potentiation: Enhancement of action of
one drug by another.
Example: Alcohol enhances the analgesic effect of
aspirin.
ii)Indirect pharmacodynamic interactions: Interactions
in which both the object and the precipitant drugs
have unrelated effects but the latter in some way
alters the effect of the former.
Example: Salicylates decreases the ability of the
platelets to aggregate thus impairing the
homeostasis if warfarin induced bleeding occurs.

26. • Ultimate consequences of drug
interactions may be;
Major : Life threatening
Minor: Deterioration of patient’s status
Moderate: Little effect

27. Reducing The Risk Of Drug
Interactions
1.Identify patient’s risk factors.
2.Take patient’s thorough drug history.
3.Keeping knowledge of the drugs being used.
4.Avoid therapeutic regimens when possible.
5.Educate the patients.
6.Monitor therapy.
7.Individualize therapy.

28. THANK YOU!