A Textbook of Clinical Pharmacology and Therapeutics

●Introduction 71

●Useful interactions 72

●Trivial interactions 72

●Harmful interactions 73

CHAPTER 13

DRUG INTERACTIONS

INTRODUCTION

Drug interaction is the modification of the action of one drug
by another. There are three kinds of mechanism:

1. pharmaceutical;
   2.pharmacodynamic;
   3.pharmacokinetic.

Pharmaceutical interactions occur by chemical reaction or
physical interaction when drugs are mixed. Pharmacodynamic
interactions occur when different drugs each infuence the same
physiological function (e.g. drugs that influence state of alert-
ness or blood pressure); the result of adding a second such
drug during treatment with another may be to increase the
effect of the first (e.g. alcohol increases sleepiness caused by
benzodiazepines). Conversely, for drugs with opposing
actions, the result may be to reduce the effect of the first (e.g.
indometacinincreases blood pressure in hypertensive patients
treated with an antihypertensive drug such as losartan).
Pharmacokinetic interactions occur when one drug affects the
pharmocokinetics of another (e.g. by reducing its elimin-ation
from the body or by inhibiting its metabolism). These mecha-
nisms are discussed more fully below in the section on adverse
interactions grouped by mechanism. A drug interaction can
result from one or a combination of these mechanisms.
Drug interaction is important because, whereas judicious
use of more than one drug at a time can greatly benefit
patients, adverse interactions are not uncommon, and may be
catastrophic, yet are often avoidable. Multiple drug use
(‘polypharmacy’) is extremely common, so the potential for
drug interaction is enormous. One study showed that on
average 14 drugs were prescribed to medical in-patients
per admission (one patient received 36 different drugs). The
problem is likely to get worse, for several reasons.

1. Many drugs are not curative, but rather ameliorate chronic
   conditions (e.g. arthritis). The populations of western
   countries are ageing, and elderly individuals not
   uncommonly have several co-morbid conditions.
   2.It is all too easy to enter an iatrogenic spiral in which a
   drug results in an adverse effect that is countered by the

introduction of another drug, and so on. Prescribers

should heed the moral of the nursery rhyme about the old

lady who swallowed a fly! Hospital admission provides

an opportunity to review all medications that any patient

is receiving, to ensure that the overall regimen is rational.

Out-patients also often receive several prescribed drugs, plus

proprietary over-the-counter medicines, ‘alternative’ remedies

60

50

40

30

Percentage of patients with

adverse drug reactions

Mortalityrate (%)

Average hospital

stay (days)

20

10

10

6

2

0

04

1–10 11–15 16 

8121620

(a) Number of drugs administered

(b)

(c)

Number of drugs administered

30

20

10

1–10 11–15 16 

Number of drugs administered

Figure 13.1:Relationship of number of drugs administered to

(a) adverse drug reactions, (b) mortality rate and (c) average

duration of hospital stay. (Redrawn by permission of the British

Medical Journal from Smith JW et al. Annals of Internal Medicine

1966; 65 : 631.)