Clinical Pharmacology and Therapeutics

CHAPTER 7
EFFECTS OF DISEASE ON DRUG
DISPOSITION
● Introduction 34
● Gastro-intestinal disease 34
● Cardiac failure 34
● Renal disease 35
● Liver disease 37
● Thyroid disease 38
INTRODUCTION
Several common disorders influence the way in which the
body handles drugs and these must be considered before prescribing.
Gastro-intestinal, cardiac, renal, liver and thyroid
disorders all influence drug pharmacokinetics, and individualization
of therapy is very important in such patients.
GASTRO-INTESTINAL DISEASE
Gastro-intestinal disease alters the absorption of orally administered
drugs. This can cause therapeutic failure, so alternative
routes of administration (Chapter 4) are sometimes needed.
Table 7.1: Pathological factors influencing the rate of gastric emptying
Decreased rate
Increased rate
Trauma
Duodenal ulcer
Pain (including myocardial
Gastroenterostomy
infarction, acute abdomen) Coeliac disease
Diabetic neuropathy
Drugs, e.g. metoclopramide
Labour
Migraine
Myxoedema
Raised intracranial pressure
Intestinal obstruction
Gastric ulcer
Anti-muscarinic drugs
GASTRIC EMPTYING
Gastric emptying is an important determinant of the rate and
sometimes also the extent of drug absorption. Several pathological
factors alter gastric emptying (Table 7.1). However,
there is little detailed information about the effect of disease
on drug absorption, in contrast to effects of drugs that slow
gastric emptying (e.g. anti-muscarinic drugs) which delay
C max . Absorption of analgesics is delayed in migraine, and a
more rapid absorption can be achieved by administering analgesics
with metoclopramide, which increases gastric emptying.
SMALL INTESTINAL AND PANCREATIC DISEASE
The very large absorptive surface of the small intestine provides
a substantial functional reserve, so even extensive
involvement with, for example, coeliac disease may be present
without causing a clinically important reduction in drug
absorption. Crohn’s disease typically affects the terminal
ileum. Absorption of several antibiotics actually increases in
Crohn’s disease. Cystic fibrosis, because of its effects on
pancreatic secretions and bile flow, can impair the absorption
of fat-soluble vitamins. Significant reductions in the absorption
of cefalexin occur in cystic fibrosis, necessitating increased
doses in such patients. Patients with small bowel resection
may absorb lipophilic drugs poorly.
CARDIAC FAILURE
Cardiac failure affects pharmacokinetics in several ways and
these are discussed below.
ABSORPTION
Absorption of some drugs (e.g. furosemide) is altered in cardiac
failure because of mucosal oedema and reduced gastrointestinal
blood flow. Splanchnic vasoconstriction accompanies
cardiac failure as an adaptive response redistributing blood to
more vital organs.