This document outlines different types of drug interactions. It begins by discussing the importance of studying drug interactions, noting that adverse drug reactions are a leading cause of death and most are due to drug interactions. It then defines a drug interaction as when one substance affects another drug's activity. Drug interactions can increase or decrease a drug's effects and can be pharmacokinetic, involving absorption, distribution, metabolism or excretion, or pharmacodynamic. The document provides examples of different types of interactions and notes that the risk of an interaction rises with the number of drugs a patient takes.

2. OUTLINE

DRUG INTERACTIONS - INTRODUCTION

DRUG – DRUG INTERACTIONS

FOOD – DRUG INTERACTIONS

3. DO WE REALLY NEED TO
STUDY DRUG
INTERACTIONS?

4. 
Meta analysis of 39 prospective clinical trials
has proved : Adverse Drug Reactions are 4th
most frequent cause of death1

Analysis of USA National Drug Register has
proved : The cause of 2/3 of ADRs are drug
interactions2
1Lazarou
2Phillips
et al: JAMA 1998
et al: JAMA 2001

5. DEFINITION
A
drug interaction
is a situation in
which a substance
affects the activity
of a drug, i.e. the
effects are
increased or
decreased, or they
produce a new
effect that neither

6. Effects of drug interaction

Drug interaction can result in
 Increased
effect – Additive or
Synergistic effect
 Increased
therapeutic effect
 Increased
toxic or adverse effect
good
bad
 Decreased
effect
effect – Antagonistic
 Decreased
therapeutic effect
 Decreased
toxic effect
bad
good

7. EXAMPLES

Synergistic drug-drug interaction : xanax is a drug which
belongs to benzodiazepine class of drugs ,if it is taken
along with an antidepressant like Prothiadine , the
drowsiness effect of both drugs is enhanced and
multiplied.

antagonistic drug-drug interaction : Ibuprofen enhances
salt retention by the body and the diuretic like furosemide
gets the body rid of the salt.

9. DIFFERENT KINDS OF DRUG
INTERACTION
PHARMACOKINETIC (PK)
Drug interactions:
PHARMACODYNAMIC (PD)

Interaction drug - drug

Interaction drug - alcohol

Interaction drug - foods (and soft drinks)

Interaction drug – food supplements
All these kinds are divided into:
Drug interactions:

clinically relevant

not clinically relevant

11. PHARMACOKINETIC INTERACTION



Most drug interactions involve an
alteration in the pharmacokinetics of the
drug.
Probably no ‘overlap’ in the therapeutic
effects of the two drugs.
Difficult to predict
1.
Absorption
2.
Distribution
3.
Metabolism
4.
Excretion

12. Drug
absorption
Transport of
the drug inside
the body
Drug
displacement
(protein-binding)
Drug metabolism
(biotransformation)
CYP3A4, CYP2D6,
CYP2C9…
Drug
excretion

13. Drug Absorption
 Drug
interactions can either delay the onset
of drug action or increase or decrease the
amount of drug absorbed.
 Rate
of drug absorption is a concern when a
fast onset of absorption is necessary.
 An
example of this would be analgesics. A
rapid response is often desired when the
patient is in pain.
 This
is important because it can ultimately
affect drug levels.

15. Distribution

When the drug leaves the systemic
circulation and moves to various parts of
the body

Drugs in the bloodstream are often
bound to plasma proteins; only
unbound drugs can leave the blood
and affect target organs

Low serum albumin can increase
availability of drugs and potentiate their
effects

16. Metabolism
(biotransformation)

Primarily in the liver; cytochrome P-450 enzyme
system facilitates drug metabolism; metabolism
generally changes fat soluble compounds to
water soluble compounds that can be excreted

Foods or dietary supplements that increase or
inhibit these enzyme systems can change the
rate or extent of drug metabolism

17. Excretion
• Drug interactions that involve
excretion can affect the amount
of drug that is either secreted or
reabsorbed.
• Some strong acids/bases are actively
secreted/reabsorbed by renal tubules.
• Digoxin excretion may be reduced by
verapamil and quinidine.Some drugs sensitive
to changes in urinary pH or sodium balance.

18. Pharmacodynamic
mechanisms

Two drugs acting upon the same (or similar)
mechanism in the same ‘direction’ (i.e. two
agonists).
 E.g.
Two beta-blockers additive
 E.g. Morphine plus diazepam additive
 E.g.

Pen-G plus gentamicin synergistic
Two drugs acting upon the same (or similar)
mechanism in opposite ‘directions’ (i.e.
agonist plus antagonist).
 E.g.
Beta-blocker plus salbutamol antagonistic
 E.g. Frusemide plus NSAID indirectly antagonistic

19. Probability of drug interaction
risk of drug interaction
60%
50%
40%
30%
20%
10%
0%
2
5
10
15
20
number of drugs used
Probability of drug interaction rises with the
number of drugs patient uses

20. More drug = More interactions