A Textbook of Clinical Pharmacology and Therapeutics

pancreatic secretions and bile flow, can impair the absorption

of fat-soluble vitamins. Significant reductions in the absorption

ofcefalexinoccur 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 car-

diac failure because of mucosal oedema and reducedgastro-

intestinal blood flow. Splanchnic vasoconstriction accompanies

cardiac failure as an adaptive response redistributing blood to

more vital organs.

●Introduction 34

●Gastro-intestinal disease 34

●Cardiac failure 34

●Renal disease 35

●Liver disease 37

●Thyroid disease 38

CHAPTER 7

EFFECTS OF DISEASE ON DRUG

DISPOSITION

INTRODUCTION

Several common disorders influence the way in which the
body handles drugs and these must be considered before pre-
scribing. Gastro-intestinal, cardiac, renal, liver and thyroid
disorders all influence drug pharmacokinetics, and individu-
alization of therapy is very important in such patients.

GASTRO-INTESTINAL DISEASE

Gastro-intestinal disease alters the absorption of orally admin-
istered drugs. This can cause therapeutic failure, so alternative
routes of administration (Chapter 4) are sometimes needed.

GASTRIC EMPTYING

Gastric emptying is an important determinant of the rate and
sometimes also the extent of drug absorption. Several patho-
logical 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
Cmax. Absorption of analgesics is delayed in migraine, and a
more rapid absorption can be achieved by administeringanal-
gesics with metoclopramide, which increases gastric emptying.

SMALL INTESTINAL AND PANCREATIC DISEASE

The very large absorptive surface of the small intestine pro-
vides 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

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