Drug-induced Gastrointestinal Disorders

[Guest guest]

Linda G. Tolstoi, RPh, MS, MEdMedscape Pharmacotherapy 4(1), 2002. ©

2002

Medscape

http://www.medscape.com/viewarticle/437034

 

Abstract and Introduction

 

AbstractThe gastrointestinal tract is frequently the site of

complications

resulting from prescription and over-the-counter drug use. If

unrecognized

or untreated, over time, these complications have the potential to

affect

nutritional status. Healthcare professionals need to be aware of the

drugs

commonly implicated in causing gastrointestinal complaints in order to

prevent long-term complications. Patients should be alerted to the

early

warning signs of drug-induced gastrointestinal disorders so that they

can

seek care and prevent long-term complications.IntroductionIn the

United

States, the 1.5 billion or more prescriptions dispensed each year

play an

important role in managing disease.[1] However, medications are

associated

with an increasing incidence of drug-induced (iatrogenic)

complications. The

gastrointestinal tract (GI) is frequently the site of such

complications.[1]

According to one study, the gastrointestinal tract was associated

with 20%

to 40% of the drug-induced adverse effects.[2]Many gastrointestinal

side

effects, such as nausea, vomiting, dyspepsia, abdominal cramps,

diarrhea, or

constipation, occur without any identifiable lesion or cause.[1]

Usually,

these effects are transient and resolve shortly after the drug is

discontinued. However, there are some widely prescribed drugs that

cause

serious and lasting adverse effects (mucosal ulceration, stricture, or

increased susceptibility to pseudomembranous colitis).[1,3] In some

situations, the adverse effects are worse than the illness for which

the

drug was prescribed.[1]This review provides an overview of some common

drug-induced gastrointestinal effects. Over time, these adverse

effects may

impact a patient's nutritional status. The elderly are most

susceptible to

these effects.

 

 

Gastrointestinal Tract

 

Oral Cavity Taste disturbance. In the elderly, drug-induced taste

disturbances include a reduced (hypogeusia) or a distorted

(dysgeusia) sense

of taste, rather than a total absence (ageusia) of taste.[4] The

mechanism

of action of drug-induced alterations in the sense of taste is not

known and

may involve different areas including peripheral receptors,

chemosensory

neuronal pathways, and/or the brain.[4] Disturbances in the sense of

taste

are usually reversible upon discontinuation of the drug, although

resolution

may take several months.[5]Taste disorders may decrease the patient's

nutritional and caloric intake.[4,6] In addition, taste disorders can

alter

digestion by affecting salivary and pancreatic flow, gastric

contraction,

and intestinal peristalsis.[6]Xerostomia. Xerostomia (dry mouth),

also known

as salivary gland hypofunction, is an uncomfortable oral symptom that

results from decreased secretion of saliva.[7] The prevalence of

drug-induced xerostomia depends upon the total number of xerogenic and

nonxerogenic drugs that are administered concurrently. Drugs that

have the

potential to cause xerostomia include antiarrhythmics,

anticholinergic and

antispasmodic agents, antihistamines, antihyperlipidemics, anti-

inflammatory

agents, antiulcer agents, coronary vasodilators, drugs for

parkinsonism, and

psychotropic drugs.[7]Drug-induced xerostomia may or may not involve

changes

in neural control of salivation.[7] For example, diuretic-induced

dehydration can induce xerostomia. Drug-induced xerostomia is

potentially

reversible, as the drugs usually do not cause permanent damage to the

salivary glands.[8]Xerostomia can have a major effect on a patient's

nutritional status.[9] Lack of saliva can make it difficult for the

patient

to speak (dysphonia), taste (ageusia), chew, and swallow food

(dysphagia).[8] Atrophy of the oral epithelium is a complication of

xerostomia that is characterized by mucositis, inflammation, fissures,

ulceration, a burning sensation in the mouth, a sore tongue, and

gingivitis.[8] Related changes in the oral microflora can increase the

patient's susceptibility to oral candidiasis.Drug-induced oral

lesions.

Drugs induce a variety of oral lesions that occur in all age groups

and can

mimic many dermatologic diseases.[10] One example is erythema

multiforme,

which primarily affects the lips and the anterior part of the mouth,

making

it difficult to eat.[10,11] Drugs commonly associated with erythema

multiforme include trimethoprim-sulfamethoxazole, sulfonamides,

penicillins,

nonsteroidal anti-inflammatory drugs (NSAIDs), and

carbamazepine.[11]Gingival enlargement. Gingival enlargement is an

overgrowth of the periodontal tissue.[12] In severe cases, the gingiva

covers nearly all of the tooth.[10] Clinical signs and symptoms

include

pain, tenderness, and gingival bleeding.[5] Drugs known to cause

gingival

enlargement include phenytoin, cyclosporine, and calcium channel

blockers

(eg, nifedipine).[12] Surgical removal of the gingival tissue is the

only

treatment in patients for whom reduction in dosage, discontinuation,

or

substitution of the drug is not possible.[12] Gingival enlargement

recurs if

the drug is not discontinued.[10]

 

 

Drug-induced Esophageal Damage

 

IrritationDrug-induced esophageal injury is common in today's

medication-oriented society.[13] Nonchewable tablets or capsules

usually

pass quickly through the esophagus and release their contents in the

stomach

or lower in the intestines.[14] Occasionally, these tablets and

capsules can

get lodged within the esophagus, dissolve, and release their

concentrated

contents, causing direct mucosal damage.[14] An important warning

sign is a

dull, aching pain in the chest or shoulder after taking the drug.[15]

The

severity of drug-induced esophageal damage ranges from mild,

asymptomatic

inflammatory changes to severe ulceration and stricture formation.

[16] The

acute forms are the most common, are self-limited, and do not lead to

serious medical problems.[16] Within 10 days after stopping the drug,

the

patient is usually asymptomatic.[16]Many factors influence the

severity of

drug-induced injury to the esophagus.[16] Chemical and physical

properties

of the drug, such as its chemical formula, pH, concentration of

medication,

drug formulation, and size and shape of the tablet or capsule, play a

role.

Other factors include delay in transit time of the drug and duration

of

contact with esophageal mucosa. When gelatin capsules are

administered with

inadequate liquid, they may become sticky as they dissolve and delay

transit

time of the drug.[17] When a gelatin capsule becomes lodged in the

esophagus, it may be difficult to dislodge with repeated swallows of

water.[17] Preexisting swallowing problems (esophageal dysmotility

conditions, stroke) or anatomical abnormalities (esophageal

strictures) may

alter the passage of the drug to the stomach.[15]Almost 100 different

drugs

are known to cause esophageal damage.[14] Aspirin, tetracycline,

quinidine,

potassium chloride, vitamin C, and iron all cause esophageal ulcers.

[15]

Alendronate can cause esophagitis, including severe ulcerations.[18]

Patients should take alendronate with at least 180 mL of water and

remain in

an upright position for at least 30 minutes before eating to prevent

esophageal ulceration.The best treatment for drug-induced esophageal

damage

is the discontinuation of the problematic drug.[17] Patients should

also

avoid irritating foods such as citrus juices and alcohol.[17]Table 1

<http://www.medscape.com/content/2002/00/43/70/437034/437034_tab.html#

Table

1.> provides patient education for the prevention of esophageal

irritation.[15]Gastroesophageal Reflux Disease (GERD)GERD occurs as a

result

of excessive exposure of the esophageal mucosa to the acidic gastric

contents.[19] The signs and symptoms of GERD range in severity from

heartburn to severe erosive esophagitis.[20]The etiology of GERD is

multifactorial.[19] Contributing factors include an atonic lower

esophageal

sphincter (LES), hiatal hernia, impaired motility of the esophagus,

lessened

resistance of the esophageal epithelium to injury, increased gastric

secretion, and delayed gastric emptying.[19]Normally, the LES, with a

zone

of pressure of 15-35 mm Hg, prevents the gastric contents from

entering the

esophagus.[21] Some drugs (eg, anticholinergics, calcium channel

blockers,

ethanol, and nitrates) cause gastroesophageal reflux by

inappropriately

relaxing the LES.[22] Progesterone, theophylline, and tricyclic

antidepressants also reduce LES pressure.[19]Treatment of drug-

induced GERD

includes reducing the dosage of the drug or discontinuing the

offending

drug.[20]

 

 

Stomach

 

Nausea and VomitingNausea and vomiting, common side effects of drugs,

usually occur early in the course of pharmacologic therapy.[23]

Often, the

symptoms will disappear with continued use. In some instances,

concurrent

administration of antiemetics may be needed to prevent dehydration and

electrolyte imbalances.[5,24] Nausea and vomiting are not always

simple

adverse effects; in some instances, the nausea and vomiting are a

sign of a

more serious situation. For example, nausea and vomiting associated

with

digoxin or theophylline may be a sign of drug toxicity.[5]Both the

vomiting

center (VC) and the chemoreceptor trigger zone (CTZ) in the brain

play an

important role in inducing vomiting.[24] The vomiting center receives

neural

impulses from different sites in the body such as the CTZ and GI

tract.

Chemotherapy administration appears to induce vomiting by directly

damaging

cells in the GI tract.[24] This is followed by the release of

significant

amounts of serotonin, a neurotransmitter, from enterochromaffin cells

in the

GI tract. When the serotonin binds to serotonin (5-HT3) receptors in

the

wall of the GI tract, neural impulses are sent to the VC.[24]Many

factors

contribute to the severity of chemotherapy-induced vomiting.[24] Each

drug

has a specific emetogenic potential (eg, minimal, moderate, high).

[24] For

example, cisplatin has a high emetogenic potential and vinblastine has

minimal emetogenic potential. Depending on the chemotherapeutic drug,

the

emetogenic potential can increase with escalating dose.[24] The

emetogenic

potential of cyclophosphamide can be moderate or high depending upon

the

dose. When chemotherapeutic drugs such as cyclophosphamide and

doxorubicin

are coadministered, the emetogenic potential is greater than that of

either

drug alone.[24] Chemotherapy-induced vomiting is more common in

females and

younger patients.[24]Delayed Gastric EmptyingTable 2

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Table

2.> lists the warning signs of delayed gastric emptying.[15] Drugs

that

have an anticholinergic effect slow down gastric neural and muscular

activity and cause the stomach to empty its contents into the

duodenum at a

slower rate than normal.[15] Some drugs prescribed to treat

Parkinson's

disease and depression may cause delayed gastric emptying.

Stomach and Duodenum

 

NSAID-Induced Gastroduodenal Mucosal InjuryIn the United States, an

estimated 13 million people use nonsteroidal anti-inflammatory drugs

(NSAIDs) on a regular basis.[25] Approximately 70 million

prescriptions are

written each year, and 30 billion over-the-counter (OTC) NSAIDs are

sold

annually.[25] The widespread use of NSAIDs has led to an increased

prevalence of NSAID-induced gastrointestinal injury.[26] The

availability of

NSAIDs as a nonprescription item adds to the incidence of

gastrointestinal

injury because patients may consume higher than recommended doses of

NSAIDs.[26] Unfortunately, patients who experience adverse

gastrointestinal

side effects often self-medicate with other OTC drugs (eg, antacids,

H2-antagonists) instead of seeking medical advice,[26] and their

diagnosis

is often missed (see Table 3

<http://www.medscape.com/content/2002/00/43/70/437034/437034_tab.html#

Table

3.> ).[15]The pathogenesis of NSAID-induced gastroduodenal mucosal

injury is

complex.[27,28] The dual-injury hypothesis suggests that both NSAID-

mediated

direct acidic damage and the suppression of prostaglandin synthesis

are

necessary to induce gastric damage.[27] Initially, the acidic

properties of

NSAIDs induce topical mucosal injury to the gastroduodenum. The active

hepatic metabolites of NSAIDs and the NSAID-related decrease in

gastric

mucosal prostaglandins indirectly contribute to cause gastroduodenal

mucosal

injury.[27,28] When the hepatic metabolites in the bile are secreted

into

the duodenum, they cause mucosal damage to the stomach by

duodenogastric

reflux and to the small intestine by antegrade passage through the GI

tract.[28]Prostaglandins maintain an intact gastric mucosal barrier by

increasing secretion of mucus and bicarbonate, maintaining mucosal

blood

flow, and decreasing acid secretion.[29] Suppression of prostaglandin

synthesis can occur systemically with both oral and parenteral NSAID

therapy.[26] The antiplatelet activity of some NSAIDs in low doses

may cause

bleeding from preexisting ulcers.[30]Researchers have discovered that

2

isoforms of the enzyme prostaglandin synthase or cyclooxygenase (COX)

exist

and that NSAIDs inhibit both isoforms.[31] The isoform COX-1 produces

protective prostaglandins in the stomach and the isoform COX-2 is

inducible

at sites of inflammation.[31,32] Researchers developed a new type of

NSAID

that specifically inhibits COX-2 while sparing COX-1.[31] In theory,

selective COX-2 inhibitors should provide the analgesic and

anti-inflammatory effects of older NSAIDs with a reduced risk of GI

injury.[25] However, within a few months of marketing, physicians

reported a

case of NSAID-associated gastropathy with celecoxib (a COX-2

inhibitor).[32]When NSAIDs irritate the gastric mucosa, they weaken

the

resistance to acid, causing gastritis, ulcers, bleeding, or

perforation.[15]

The damage ranges from superficial injury to single or multiple

ulcers, some

of which may bleed. The clinical signs and symptoms of NSAID-induced

gastropathy include dyspepsia, diarrhea, and nausea and vomiting.[29]

Since

these do not always correlate with the severity of the mucosal damage,

[29]

patients, especially the elderly, need to understand the prudent use

of

NSAIDs to prevent serious complications.[26]Elderly patients are

especially

at risk for NSAID-induced gastroduodenal mucosal injury because of

their

multiple medical conditions and polypharmacy. Risk factors include

concomitant corticosteroid or anticoagulant therapy, high doses of

NSAIDs,

and long-term NSAID therapy.[5] Patients with a history of peptic

ulcer

disease, Helicobacter pylori infection, or gastritis are also at

risk.[15]The various NSAIDs differ with regard to their risk of

inducing

upper GI bleeding and/or perforation.[33,34] Commonly prescribed

NSAIDs such

as ibuprofen and diclofenac appear to have the lowest relative risk.

[33]

Sulindac, aspirin, naproxen, and indomethacin have an intermediate

relative

risk, and piroxicam has the highest relative risk.[33] A reason for

these

differences may be related to dose.[34]

 

 

Small Intestine

 

In the small intestine, drugs can cause ulcers, hemorrhage,

malabsorption,

and intestinal dysmotility. They can also produce cytotoxic effects

on the

intestinal mucosal cells.[23]UlcersNSAIDs and potassium supplements

are the

primary culprits of drug-induced ulcers of the small intestine.[23]

Risk

factors for NSAID-induced ulcers include age > 60 years, a previous

history

of NSAID complications, and concomitant corticosteroid therapy.[23]

Like

NSAIDs, potassium can cause direct irritation to the mucosal lining.

Enteric-coated potassium chloride was formulated to resist the acidic

environment of the stomach.[2] However, when the enteric-coated

tablets

dissolve in the small intestines, a high concentration of ionized

potassium

accumulates adjacent to the dissolving tablet and causes direct

epithelial

damage and mucosal ischemia as a result of local vasoconstriction.

[35] These

changes in the epithelium and mucosa lead to ulceration, bleeding, or

perforation.[35] In addition, a stricture may develop secondary to

fibrosis

associated with the healing process. To prevent this damage, the

formulations of potassium chloride tablets were changed to a

controlled-release wax matrix system and to microencapsulation to

reduce the

risk of injuring the gastrointestinal mucosa.HemorrhageAnticoagulants

may

cause gastrointestinal hemorrhage.[23] Risk factors include intensity

of

therapy, adequacy of monitoring dosage, route of administration,

concurrent

pharmacotherapy, and the patient's age and underlying clinical status.

[23]

GI bleeding associated with anticoagulant therapy usually occurs in

patients

with preexisting intestinal lesions. The clinical features of

anticoagulant-induced hemorrhage include hematemesis, melena, and

hematochezia.[23]MalabsorptionDrug-induced malabsorption interferes

with the

absorption of specific nutrients. For example, tetracycline chelates

calcium, cholestyramine binds iron and vitamin B12, mineral oil

reduces the

absorption of carotene and fat-soluble vitamins, thiazide diuretics

impair

ileal transport of sodium, and aluminum/magnesium hydroxide

precipitate

calcium and phosphate ions.[23] Colchicine, neomycin, methotrexate,

methyldopa, and allopurinol interfere with absorption of nutrients by

causing mucosal damage. Drug-induced malabsorption may exacerbate the

patient's poor nutritional status.[23]DysmotilityThe motor activity

of the

small intestine is less likely to be affected by drugs than is the

colon.[23] However, drugs such as phenothiazines, antiparkinsonian

agents,

tricyclic antidepressants, anticholinergics, opiates, loperamide, and

calcium channel blockers can also inhibit the motility of the small

intestine.[23] The reduction of small bowel motility may be severe

enough

that it can cause paralytic ileus or pseudo-obstruction.[5] Paralytic

ileus

is usually temporary and is associated with abdominal distention and

symptoms of acute obstruction. Loperamide, an antidiarrheal drug, may

cause

paralytic ileus.[5] Vincristine, a chemotherapeutic agent, may cause

pseudo-obstruction probably as a result of its neurotoxic effects on

enteric

motor function.[5,23] Intestinal motility usually returns shortly

after

discontinuation of the drug.[23]Cytotoxic EffectsMany

chemotherapeutic drugs

have cytotoxic effects on mucosal cells of the small intestine

because these

cells have a high turnover rate.[23] Chemotherapeutic drugs such as

actinomycin D, bleomycin, cytosine, arabinoside, doxorubicin,

5-fluorouracil, methotrexate, and vincristine can cause erosive

enteritis.

The clinical features include pain, bleeding, vomiting, ileus, and

diarrhea.[23]

Large Intestine

 

The colon is also affected by many different drugs, but the drug-

induced

radiographic abnormalities in the colon develop over a longer period

of time

and the clinical symptoms are more insidious than they are in the

upper GI

tract.[36]Cathartic ColonCathartic colon is the anatomic and

physiologic

change in the colon that occurs with chronic use of stimulant

laxatives (> 3

times per week for at least 1 year).[37] Signs and symptoms of

cathartic

colon include bloating, a feeling of fullness, abdominal pain, and

incomplete fecal evacuation.[23] Radiologic studies show an atonic and

redundant colon.[36] Chronic use of stimulant laxatives can lead to

serious

medical consequences such as fluid and electrolyte imbalance,

steatorrhea,

protein-losing gastroenteropathy, osteomalacia, and vitamin and

mineral

deficiencies.[38] When the drug is discontinued, radiographic and

functional

changes in the colon may only partially return to normal because of

drug-induced neuromuscular damage to the colon.[39]Anthranoid

laxatives

(aloe, cascara sagrada, and senna) are derived from naturally

occurring

plants and are considered to be stimulant laxatives. Short-term use of

stimulant laxatives is safe,[40] but abuse of these drugs can cause

melanosis coli[39] and possibly increases the risk of colonic cancer.

[40]

Melanosis coli, a benign condition, is characterized by dark

pigmentation of

the colonic mucosa that usually develops 9 months after initiating

the use

of these drugs and disappears just as quickly after the drug is

discontinued.[23]DiarrheaDrugs induce diarrhea by disrupting the

normal

physiologic processes that regulate fluid absorption and secretion, by

altering GI defense mechanisms, and by damaging the mucosa of the

small and

large intestine.[41]Specifically, drugs can cause diarrhea by

interfering

with normal physiologic processes that play a role in fluid and

electrolyte

balance within the GI tract.[41] For example, drugs can interfere

with the

Na+- K+ pump that regulates the active transport of water and

electrolytes

across the cell membrane. A drug can inhibit the enzyme Na+-K+-ATPase

so

that energy cannot be released from adenosine triphosphate (ATP). The

inhibition of the ileal and colonic Na+-K+ pump causes decreased fluid

absorption and diarrhea.[41]Antibiotics are a common cause of

diarrhea.

Antibiotics affect the bacteria that normally exist in the large

intestine.[15] Broad-spectrum antibiotics kill both the pathogenic and

normal colonic flora.[41] A consequence of antibiotic therapy is

Clostridium

difficile-associated diarrhea (CDAD).[42]C difficile-associated

diarrhea

occurs because the antibiotic allows the overgrowth of C difficile,

which

does not typically colonize the colon of a healthy adult.[42]

Although most

antibiotics can cause CDAD,[15] the antibiotics most commonly

associated

with CDAD are clindamycin, ampicillin, amoxicillin, and the

cephalosporins.[42] Other antibiotics associated with CDAD, but less

frequently, include erythromycin, other penicillins, quinolones, and

trimethoprim-sulfamethoxazole. Multiple courses of antibiotics or

repeated

antibiotic therapy increase the risk of infection.[5]C difficile-

associated

diarrhea can occur as a result of both oral and parenteral antibiotic

therapy.[42]Management of a mild case of CDAD involves

discontinuation of

the antibiotic and may include fluid and electrolyte replacement

therapy.[42] If the patient requires continued antibiotic therapy, a

different antibiotic that is less likely to cause CDAD should be

prescribed.Drug-induced diarrhea is common in the elderly because of

age-related factors and the number of medications used to treat acute

and

chronic diseases.[41] An age-related decrease in both the immune and

nonimmune defense mechanisms increases the patient's susceptibility to

intestinal infections (eg, viral, bacterial, protozoal) that cause

diarrhea.[41] Early diagnosis and treatment of diarrhea in the

elderly is

important to prevent dehydration, loss of electrolytes, and

deterioration of

the patient's nutritional status.NSAID-Induced ColitisNSAIDs may cause

colitis or exacerbate a preexisting colonic disease,[43] but the

mechanism

(local or systemic) is unclear. Patients experience bloody diarrhea,

weight

loss, fatigue, and chronic iron deficiency anemia. When the drug is

discontinued, the NSAID-induced colitis improves.[23]

Management

 

Many drugs can adversely affect the GI tract. Because these adverse

effects

may affect a patient's nutritional status over time, healthcare

professionals need to be aware when these drugs are prescribed or

used OTC.

Whenever possible, the offending drug should be discontinued and an

alternative prescribed. Discontinuation and prescription of another

drug

without such side effects is the first line of defense for managing

drug-induced GI disorders. However, a reduction in dose may be

sufficient if

therapy with a specific drug is necessary. Taking the drug with food

may

also help to reduce the possibility of side effects. Avoidance of

irritating

foods and beverages is also suggested.Patients with symptoms of

delayed

gastric emptying should eat small, frequent meals, stay upright for a

half

hour after eating, and inform their physician if the symptoms

continue.[15]

Extra care should be taken when counseling an elderly client. These

patients

are often not adequately informed of the adverse effects of drugs

because of

hearing problems, poor eyesight, or cognitive impairment, and may not

be

aware that the drug is causing the adverse GI side effects.[41]

 

 

Conclusion

 

Medications play an important role in the health and well being of

patients.

Unfortunately, many medications are also associated with adverse

effects

that can have a negative impact on a patient's quality of life and

health

status. Drugs that adversely affect the GI system are especially

important

because the adverse effects, if prolonged, can ultimately produce

negative

nutritional effects. Healthcare professionals can play an important

role in

reducing the incidence of drug-induced GI disorders by alerting the

patient

to the early warning signs and providing education to help patients

prevent

these effects.

Tables

 

Table 1. Precautions to Prevent Irritation of the Esophagus

 

 

Swallow several sips of water to lubricate the throat before taking a

tablet

or capsule.

 

 

Swallow tablet or capsule with at least 8 ounces of liquid.

 

 

Swallow tablets or capsules while in an upright or sitting position.

 

 

Do not lie down immediately after taking a tablet or capsule to

ensure that

the solid dosage forms pass through the esophagus and into the

stomach.

 

 

Inform your physician if swallowing continues to be painful or if the

tablets or capsules continue to stick in the throat.

 

Table 2. Warning Signs of Delayed Gastric Emptying

 

Nausea

 

Bloating

 

Feeling of fullness

 

Vomiting of food many hours after eating

 

Mid-abdominal pain

 

Heartburn/indigestion

 

Sensation of food regurgitating into the throat

 

 

Table 3. Warning Signs of NSAID-induced Gastric Irritation

 

Severe abdominal cramps/pain

 

Burning in the stomach or back

 

Blood in the stools

 

Bloody vomit

 

Severe heartburn/indigestion

 

Diarrhea

 

 

References

 

 

Ghahremani GG. Gastrointestinal complications of drug therapy. Abdom

Imaging. 1999;24:1-2.

Gatenby RA. The radiology of drug-induced disorders in the

gastrointestinal

tract. Semin Roentgenol. 1995;30:62-76.

Bramble MG, Record CO. Drug-induced gastrointestinal disease. Drugs.

1978;15:451-463.

Schiffman SS. Taste and smell losses in normal aging and disease.

JAMA.

1997;278:1357-1362.

Lee A, Morris J. Drug-induced gastrointestinal disorders. The

Pharmaceutical

Journal. 1997;258:742-747.

Schiffman SS. Taste and smell in disease. N Engl J Med. 1983;308:1275-

1279.

Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth -

2nd ed.

Gerodontology. 1997;14:33-47.

Pray WS. Dry mouth syndrome: causes and treatment. US Pharmacist.

1994;19:16,18,20,22,24.

Boyd LD, Dwyer JT, Papas A. Nutritional implications of xerostomia and

rampant caries caused by serotonin reuptake inhibitors: a case study.

Nutr

Rev. 1997;55:362-368.

Korstanje MJ. Drug-induced mouth disorders. Clin Exp Dermatol.

1995;20:10-18.

Laskaris G, Satriano RA. Drug-induced blistering oral lesions. Clin

Dermatol. 1993;11:545-550.

Brunet L, Miranda J, Farré M, et al. Gingival enlargement induced by

drugs.

Drug Safety. 1996;15:219-231.

Levine MS. Drug-induced disorders of the esophagus. Abdom Imaging.

1999;24:3-8.

Kikendall JW. Pill-induced esophageal injury. In: Castell DO, Richter

JE,

eds. The Esophagus. Philadelphia, Pa: Lippincott Williams & Wilkins;

1999.

Harmful effects of medicines on the adult digestive system. U.S.

Department

of Health and Human Services. NIH Publication No. 97-3421, September

1992.

Boyce HW Jr. Drug-induced esophageal and gastric damage. In: Tytgat

GNJ, van

Blankenstein M, eds. Current Topics in Gastroenterology and

Hepatology. New

York, NY: Georg Thieme Verlag; 1990.

Boyce Jr HW. Drug-induced esophageal damage: diseases of medical

progress.

Gastrointest Endosc. 1998;47:547-550.

De Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with

the use

of alendronate. N Engl J Med. 1996;335:1016-1021.

Richter JE. Gastroesophageal reflux: diagnosis and management. Hosp

Pract.

1992;27:59-66.

Carruthers-Czyzewski P. GERD in older adults. CPJ/RPC. 1999;132:28-32.

Gossel TA. Gastroesophageal reflux disease. US Pharmacist.

1992;17:21-23,27-28,84.

Ross H. GERD in the elderly patient. US Pharmacist. 1994;19:80,82-

85,88.

Yamada T, Alpers DH, Owyang C, et al. Handbook of Gastroenterology.

Philadelphia, Pa: Lippincott-Raven Publishers; 1998.

Clark-Vetri RJ. Management of chemotherapy-induced emesis. Pharm

Times.

1999;65:78-85.

Graumlich JF. Preventing gastrointestinal complications of NSAIDs.

Postgrad

Med. 2001;109117-120,123-128.

Byrd DC. NSAID-induced gastropathy: prevention and treatment

strategies.

Pharm Times. 1999;65:44-50.

Schoen RT, Vender RJ. Mechanisms of nonsteroidal anti-inflammatory

drug-

induced gastric damage. Am J Med. 1989;86:449-458.

Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of

nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340:1889-1899.

Fuller SH, McKenzie C. Gastropathy. US Pharmacist.

1992;17:35-36,41-42,47-48,53-55,87.

McCarthy DM. Nonsteroid anti-inflammatory drugs - the clinical

dilemmas.

Scand J Gastroenterol. 1992;192(suppl):9-16.

Simon LS. The evolution of arthiritis inflammatory care: where are we

today?

J Rheumatol. 1999;26(suppl 56):11-17.

Mohammed S, Croom DW II. Gastropathy due to celecoxib, a

cyclooxygenase-2

inhibitor. N Engl J Med. 1999;340:2005-2006.

Henry D, Lim LL-Y, Rodríguez LA, et al. Variability in risk of

gastrointestinal complications with individual non-steroidal

anti-inflammatory drugs: results of a collaborative meta-analysis.

BMJ.

1996;312:1563-1566.

Rodríguez LA. Variability in risk of gastrointestinal complications

with

different nonsteroidal anti-inflammatory drugs. Am J Med. 1998;10430S-

34S.

Gore RM, Levine MS, Ghahremani GG. Drug-induced disorders of the

stomach and

duodenum. Abdom Imaging. 1999;24:9-16.

Neitlich JD, Burrell MI. Drug-induced disorders of the colon. Abdom

Imaging.

1999;24:23-28.

Joo JS, Ehrenpreis ED, Gonzalez L, et al. Alterations in colonic

anatomy

induced by chronic stimulant laxatives. The cathartic colon

revisited. J

Clin Gastroenterol. 1998;26:283-286.

Tolstoi LG. Nutritional problems related to stimulant laxative abuse.

Hosp

Pharm. 1988;23:564,566,568,572-573.

Lewis JH. Gastrointestinal injury due to medicinal agents. Am J

Gastroenterol. 1986;81:819-834.

Van Gorkom AP, DeVries EGE, Karrenbeld A, et al. Anthranoid laxatives

and

their potential carcinogenic effects. Aliment Pharmacol Ther.

1999;13:443-452.

Ratnaike RN, Jones TE. Mechanisms of drug-induced diarrhoea in the

elderly.

Drugs & Aging. 1998;13:245-253.

Sheff B. Minimizing the threat of C. difficile. Nursing. 1999;29:33-

38.

Faucheron J-L, Parc R. Non-steroidal anti-inflammatory drug-induced

colitis.

Int J Colorect Dis. 1996;11:99-101.

Acknowledgements

The author would like to thank the library staff at the Fayette

Campus of

the Pennsylvania State University, Uniontown, and the interlibrary

loan

staff at the Pennsylvania State University, University Park, for their

assistance.

 

Funding Information

Linda G. Tolstoi, RPh, MS, MEd, has no significant financial interest

to

disclose.

 

 

 

Linda G. Tolstoi, RPh, MS, MEd, Visiting Scholar, Department of

Biomedical

Engineering, Boston University Center for Advanced Biotechnology,

Boston,

Massachusetts.