Adverse Effects of Medications on the Upper Digestive System
Many
drugs adversely affect digestive system function or mucosal integrity.
Drug-induced liver injury is so common that we have devoted an entire section
of Part III to this topic. Although a host of medications have the unwanted
potential for injuring the liver, the wise clinician will consider all
medications as potential causes of hepatic injury. Similarly, hydralazine,
azathioprine, several agents that effectively treat HIV infections, some
antibiotics, and even steroids are known to injure the pancreas. In a patient
being evaluated for the cause of acute pancreatitis, recently started
medications should be considered; importantly, a medication taken for months
may also cause pancreatitis.
The most common mechanism of drug injury to the
digestive system is alteration of the integrity of the epithelial lining. Drugs
may have a direct injurious effect or may medicate the impaired mucosal defense
by indirect mechanisms. Thus, every assessment of a patient presenting with a
digestive organ problem must include a detailed history of both prescribed and
over-the-counter medications. This history should also include dietary
supplements and herbal agents.
The common and all-too-often life-threatening adverse
effects of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are
so important that we have discussed them in considerable detail with Plate
4-51. NSAIDs are the agents that most commonly cause mucosal injury, but a wide
variety of other unrelated drugs also cause direct mucosal injury. These
include iron supplements, potassium supplements, bisphosphonates, tetracycline
antibiotics, and quinidine. It has been shown that drinking 6 to 8 ounces of
fluid before and after swallowing these medications will reduce esophageal
injury. The theory that food may act as a buffer against the adverse effects of
these drugs in other organs is a reasonable but unproven one. Iron supplements
not only can cause mucosal injury but also may raise concern for bleeding when
the stool turns dark gray, suggesting melena. In such cases, intravenous
supplementation, although more expensive, may also be more prudent.
Drugs that are antimetabolites often interfere with
mucosal integrity by reducing the normal defenses provided by the normally
high frequency of cell turnover. This is particularly true where cell turnover
is most rapid, as in the oral epithelium, distal esophagus, and stomach;
aphthous ulcers and even mucosal sloughing can be seen in these areas.
Methotrexate and chemotherapeutic agents are most commonly associated with such
injury. Irradiation will cause a similar lesion, through the same mechanism. In
addition to this acute injury caused by inhibition of cell turnover and repair,
irradiation often leads to mucosal atrophy, submucosal bleeding, endarteropathy,
vascular ectasias, and mucosal bleeding.
Motility is commonly altered by medications. Medications
with anticholinergic side effects can impair the motility function of most, if
not all, of the luminal digestive organs, reduce esophageal clearance by reducing
peristaltic amplitude, cause increased reflux by reducing lower esophageal
sphincter tone, delay gastric emptying, and impair motility of the small and
large intestines. Caffeine primarily causes an adverse effect by selective
reduction of lower esophageal sphincter tone. Opioids most commonly lead to
gastrointestinal symptoms by causing constipation due to the density of opioid
receptors in the colon, but can also delay gastric emptying and cause
gastroparesis. The effects of anti-cholinergic drugs on the motor and
secretory activities of the intestine are sometimes the primary therapeutic aim
and sometimes an unwelcome by-product of therapy directed elsewhere. Hormones
can also impair motility. Most notably, somatostatin analogs delay gall-bladder
emptying and progesterone has an inhibitory effect on colonic contractions.
The parasympathomimetic drugs (e.g., methacholine,
bethanechol), including those agents that inhibit the hydrolysis of
acetylcholine by blocking the action of cholinesterase (e.g., neostigmine),
stimulate saliva production and gastric emptying.
Drugs that either stimulate or inhibit the
effects of sympathetic nerves are far less active on the gastrointestinal
tract than on other systems. A potent vasoactive sympathomimetic used in a
critical care setting, however, often reduces gut blood flow, particularly to
the stomach, which can lead to gastritis and delayed gastric emptying.
