GASTROINTESTINAL DRUGS

Gastrointestinal Tract

o The GI tract is responsible for food digestion and the absorption of nutrients and water. Dietary constituents
normally undergo a series of digestive processes as they progress through the GI system.

o Under normal conditions, the transit time of food and water is adequate to allow the processes of digestion and
absorption to take place. Indigestible and nonabsorbable products are eliminated by defecation.

o The GI system is susceptible to various infectious and parasitic invasions.

Drugs Used to Control Gastric Acidity and Secretion

o Antacids

o Antacids are a class of drugs used to treat conditions caused by the acid that is produced by the stomach.

o Antacids reduce acidity by neutralizing (counteracting) acid, reducing the acidity in the stomach, and
reducing the amount of acid that is refluxed into the esophagus or emptied into the duodenum.

o Rationale for Use and Mechanism of Action

o Antacids attempt to chemically neutralize stomach acids. These drugs typically contain a base such
as carbonate or hydroxide combined with aluminum, magnesium, or calcium. The base combines
with excess hydrogen ions (H!) in the stomach to increase intragastric pH.

o Antacids are frequently used to treat episodic minor gastric discomfort (indigestion, heartburn)
often accompanying overeating or indulging in certain incompatible foods.

o Antacids can also be used in the more serious and chronic conditions of peptic ulcer and chronic
gastroesophageal reflux, but large amounts of antacids must be used for prolonged periods.

o Consequently, antacids are used primarily to treat fairly minor and transient dyspepsia occurring
from overeating, eating spicy foods, and so forth.

SPECIFIC AGENTS ADVERSE EFFECT

Gaviscon Constipation
Milk of Magnesia Diarrhea
Tums
Amphojel Constipation

o H2 Receptor Blockers
o H2 blockers are a group of medicines that reduce the amount of acid produced by the cells in the
lining of the stomach. They are also called 'histamine H2-receptor antagonists' but are commonly
called H2 blockers.
o H2 blockers are commonly used:
o To reduce acid reflux which may cause heartburn or inflammation of the gullet
(oesophagitis). These conditions are sometimes called gastro-oesophageal reflux disease
(GORD).
o To treat ulcers in the stomach and in part of the gut (the duodenum).
o To help heal ulcers associated with anti-inflammatory medication called non-steroidal anti-
inflammatory drugs (NSAIDs).
 o In other conditions where it is helpful to reduce acid in the stomach.
o At one time they were used as one part of a treatment to get rid of Helicobacter pylori, a
germ (bacterium) found in the stomach, which can cause ulcers. However, proton pump
inhibitors are now preferred for this use.
o Rationale for Use and Mechanism of Action
o The regulation of gastric acid secretion involves the complex interaction of many endogenous
chemicals, including histamine.
o Histamine stimulates specific receptors on stomach parietal cells to increase gastric acid secretion.
o The H2 blockers are used for both acute and long-term management of peptic ulcer and other problems
such as dyspepsia and gastroesophageal reflux disease (GERD).
o H2 blockers remain an option for treating mild or occasional gastric irritation, but the routine use of
these drugs in serious gastric disease has been largely replaced by more effective drugs such as proton
pump inhibitors.
o SPECIFIC AGENTS
Generic Name Trade Name Adult Oral Dosage
Cimetidine Tagamet 300 mg 4 times each day with meals
and at bedtime, 400 or 600 mg in the
morning and at bedtime, or 800 mg
at bedtime
Famotidine Pepcid 40 mg once daily at bedtime or 20 mg
BID
Nizatidine Axid 300 mg once daily at bedtime or 150
mg BID
Ranitidine Zantac 150 mg twice daily or 300 mg at
bedtime

SPECIFIC AGENT ADVERSE EFFECT

Cimetidine Arthralgia, Myalgia
Famotidine Headache
Nizatidine Adverse effects are rare
Ranitidine Headache

o Proton Pump Inhibitors

o Proton pump inhibitors (PPIs) reduce the production of acid by blocking the enzyme in the wall of the
stomach that produces acid. Acid is necessary for the formation of most ulcers in the esophagus,
stomach, and duodenum, and the reduction of acid with PPIs prevents ulcers and allows any ulcers that
exist in the esophagus, stomach, and duodenum to heal.
o Rationale for Use and Mechanism of Action
o These drugs inhibit the H+, K+ -ATPase enzyme that is ultimately responsible for secreting acid
from gastric parietal cells into the lumen of the stomach.
o This enzyme is also known as the “proton pump”; hence these drugs are often referred to as
proton pump inhibitors (PPIs).
o PPIs are extremely effective at inhibiting the proton pump, and therapeutic doses can virtually
eliminate gastric acid secretion.
o There is some evidence that PPIs also have antibacterial effects against Helicobacter pylori
infection and that these drugs may have some anti-inflammatory properties that help decrease
gastric irritation.
o Evidence indicates that PPIs are more effective than H2 blockers and antacids in controlling acid
secretion and promoting the healing of ulcers.
 o PPIs have therefore gained prominence in treating gastric problems, and are now the drug of
choice in the long-term treatment of patients with gastric and duodenal ulcers and GERD.

o SPECIFIC AGENTS

o ADVERSE SIDE EFFECTS

o PPIs are usually well-tolerated. As with antacids and H2 blockers, increased secretion of gastric
acid (acid rebound) can occur when PPIs are discontinued after prolonged use.
o It has also been suggested that long term use is associated with gastric polyps and
gastrointestinal tumors.
o Antidiarrheal Agents
o An antidiarrheal is a substance used to prevent or treat diarrhea. Your doctor can prescribe an
antidiarrheal if diarrhea is your main symptom.
o Antidiarrheal drugs help control diarrhea and slow the passage of stool through the intestine.
o Diarrhea is loose, watery stools (bowel movements). You have diarrhea if you have loose stools three or
more times in one day. Acute diarrhea is diarrhea that lasts a short time. It is a common problem. It
usually lasts about one or two days, but it may last longer.
o What causes diarrhea?
The most common causes of diarrhea include
o Bacteria from contaminated food or water
o Viruses such as the flu, norovirus, or rotavirus . Rotavirus is the most common cause of acute
diarrhea in children.
o Parasites, which are tiny organisms found in contaminated food or water
o Medicines such as antibiotics, cancer drugs, and antacids that contain magnesium
o Food intolerances and sensitivities, which are problems digesting certain ingredients or foods. An
example is lactose intolerance.
o Diseases that affect the stomach, small intestine, or colon, such as Crohn's disease
o Problems with how the colon functions, such as irritable bowel syndrome
 o SPECIFIC AGENTS

o Opioid Derivatives
o Rationale for Use and Mechanism of Action
o The constipating effects of morphine and certain other opioid derivatives have been
recognized for some time.
o These drugs produce a general decrease in GI motility, and they may also reduce fluid loss
by increasing the absorption of salt and water or by decreasing fluid and electrolyte
excretion from the GI tract.
o The exact manner in which opioids exert these effects, however, is not known.
o The primary effects of opioids on GI motility (antiperistalsis), however, seem to occur
because opioids bind to neuronal receptors on the enteric nerve plexus within the gut wall
or by a direct effect of opioids on GI epithelial and smooth muscle cells.
o In particular, the mu subtype of the opioid receptor seems to be important in mediating the
GI effects of opioid drugs; stimulation of these receptors is the primary method for reducing
GI motility and treating diarrhea
o SPECIFIC AGENTS

SPECIFIC AGENTS ADVERSE EFFECTS

Opium tincture Nausea, vomiting, lightheadedness, dizziness, drowsiness,
or constipation
Opium Paregoric Weak or shallow breathing;
a light-headed feeling, like you might pass out; confusion;
or
feelings of extreme happiness or sadness
Loperamide Dizziness, drowsiness, dry mouth, vomiting, constipation,
fatigue, stomach, pain, discomfort, or enlargement
Diphenoxylate Stomach or abdominal pain or swelling, severe
nausea or vomiting
Difenoxin Drowsiness, dizziness, headache, tiredness
o Adsorbents
o Rationale for Treatment and Mechanism of Action
o Adsorbents such as kaolin, pectin, or attapulgite are administered to take up and hold
harmful substances such as bacteria and toxins in the intestinal lumen.
o Theoretically, these adsorbents sequester the harmful products that cause the diarrhea.
o These products are used frequently in minor diarrhea, although there is some doubt as to
whether they really help decrease stool production and water loss.
o SPECIFIC AGENTS

Generic Name Trade Name Dosage

Attapulgite Donnagel 1.2–1.5 gm after each loose bowel
movement
Kaolin, Pectin Kao-Spen, Kapectolin 60–120 mL regular-strength
suspension after each loose, bowel
movement

o Adverse Side Effects

o Adsorbents are essentially free from side effects, although constipation may follow
prolonged or excessive use.

o Bismuth Salicylate
o Bismuth subsalicylate is the active ingredient in the popular medication Pepto-Bismol that is used to
treat nausea, heartburn, indigestion, upset stomach, diarrhea, and other temporary discomforts of
the stomach and gastrointestinal tract.
o It is also the main ingredient of Kaopectate. It displays anti-inflammatory action (due to salicylic
acid) and also acts as an antacid and mild antibiotic.
o Rationale for Treatment and Mechanism of Action
o Bismuth salicylate has a number of properties contributing to its antidiarrheal effects.
o This drug may stimulate water and electrolyte absorption from the lower GI tract, thus
decreasing fecal fluid loss.
o In addition, the bismuth component of this compound may have antibacterial effects, and
the salicylate component may inhibit the production of prostaglandins that irritate the
intestinal lining.
o The combination of these properties makes this drug fairly effective in treating mild-to-
moderate diarrhea.
o Bismuth salicylate also decreases gastric acid secretion and exerts antacid effects, hence its
use in stomach upset and minor gastric irritation.
o As indicated earlier, bismuth compounds are also part of the antibacterial regimen in H.
pylori infection.
o Specific Agents
o Bismuth salicylate is the active ingredient in Pepto Bismol, a fairly inexpensive and readily
available overthe-counter commercial product.
o Adverse Side Effects
o This drug is relatively free from serious side effects. Problems with salicylate intoxication
may occur during overdose or in people who are sensitive to aspirin and other salicylates.
o Miscellaneous Agents Used to Treat Diarrhea
o Clonidine (Catapres)
o Octreotide (Sandostatin)
o Cholestyramine (Questran) and Colestipol (Colestid)
o Laxatives and Cathartics
o Something that promotes emptying of the bowels. Laxatives are used to combat constipation. They
are sometimes overused, producing diarrhea.
o Rationale for Use
o Laxatives are used to promote evacuation of the bowel and defecation. Cathartics, or
purgatives, are also used to promote lower GI evacuation, but in a somewhat more rapid
fashion than with typical laxatives.
o Laxatives are typically used whenever normal bowel movements have been impaired but no
obstruction exists in the GI system.
o Laxatives are also indicated for bowel evacuation prior to surgical or diagnostic procedures.
o The problem with laxatives is that they are frequently abused. The long-term, chronic use of
laxatives is usually unnecessary and often unhealthy.
o These agents are self-administered by individuals who are obsessed with maintaining daily
bowel movements.
o Consequently, laxatives serve an important but finite role in GI function, and their role in
helping maintain daily evacuation should be deemphasized.

o SPECIFIC AGENTS
 o Adverse Effects
o Disturbances in the GI system, such as nausea and cramps, may occur with laxative use.
With prolonged use, serious lower GI irritation, including spastic colitis, may occur.
o Fluid and electrolyte abnormalities are also a potential problem. Excessive loss of water and
the concomitant loss of electrolytes may transpire, resulting in dehydration and possible
acid-base imbalances.
o These abnormalities are especially significant in older or debilitated patients. Finally, chronic
administration may result in a laxative dependence when bowel evacuation has become so
subservient to laxative use that the normal mechanisms governing evacuation and
defecation are impaired.

o Miscellaneous Gastrointestinal Drugs

o Emetics
o Emetics are used to induce vomiting and are frequently administered to help empty the
stomach of poisons or ingested toxins.
o The two primary emetics are apomorphine and ipecac.
o Both agents seem to work by stimulating the medullary emetic center, and ipecac also
exerts a direct emetic effect on the stomach.

o Antiemetics

o Antiemetics are used to decrease the nausea and vomiting that are associated with motion
sickness and recovery from surgery or that develop in response to other medical
treatments, such as cancer chemotherapy and radiation treatment.

o Antiemetic agents include antihistamines (dimenhydrinate, meclizine, others),

anticholinergics (scopolamine), drugs that block specific CNS dopamine (D2) and serotonin
(5HT3) receptors, cannabinoids, and several other drugs that act at various sites in the CNS
to suppress nausea and vomiting.

o Other antiemetic drugs such as antacids and adsorbents act locally to soothe the gastric
mucosa and decrease the irritation that may cause vomiting.

o Special Concerns in Rehabilitation Patients

o Drugs affecting the GI system are important in rehabilitation patients by virtue of their frequent use.
o Drugs such as the PPIs (omeprazole, others) and H2 receptor blockers (cimetidine, ranitidine, others)
are often helpful in controlling gastric acid secretions, thus preventing damage to the mucosal lining.
o Patients seen in rehabilitation are often relatively inactive and suffer from many adverse effects of
prolonged bed rest, including constipation.
o Constipation and fecal impaction may also be a recurrent and serious problem in patients with
spinal cord injuries. Laxatives are used routinely in these patients to facilitate adequate bowel
evacuation.
o Patients receiving cancer chemotherapy often have problems with nausea and vomiting, and
antiemetic drugs may be helpful to these individuals.
o Various other GI disorders, including diarrhea and chronic indigestion, occur frequently in many
rehabilitation patients and are often treated effectively with the appropriate agents.
References
o Ciccone, Pharmacology in Rehabilitation 4th Edition
o https://www.medicinenet.com/script/main/art.asp?articlekey=6465
o https://www.drugs.com/drug-class/antacids.html
o https://www.webmd.com/heartburn-gerd/guide/treating-heartburn-over-counter-medicine
o https://medlineplus.gov/ency/patientinstructions/000382.htm
o https://www.webmd.com/drugs/2/drug-76860-769/antacid-oral/aluminum-magnesium-antacid-simethicone-
oral/details
o https://www.drugs.com/drug-class/antidiarrheals.html
o https://medlineplus.gov/diarrhea.html
o https://www.everydayhealth.com/drugs/loperamide