DRUGS FOR THE

GASTROINTESTINAL
SYSTEM

Drugs Used in Acid-Peptic

Disease
GERD, gastric and duodenal peptic ulcers, and stressrelated mucosal injury.
reduce intragastric acidity
controlling hydrogen acid secretion
Promote mucosal defense
eradicate H. pylori (80% of duodenal ulcers)

Antacids, H2-receptor antagonist, PPI, mucosal

protective agents (sucralfate, misoprostol, bismuth),
antibiotics (CHECKLIST)

ANTACIDS
weak bases that neutralize stomach acid by reacting
with protons in the lumen of the gut and may also
stimulate the protective functions of the gastric mucosa
Mg (OH)2 laxative; Al (OH)3 constipation
CaCO3 and NaHCO3 systemically absorbed

H2-RECEPTOR ANTAGONISTS
Cimetidine, ranitidine, famotidine, nizatidine
H2 receptorThis Gs-coupled receptor mediates
gastric acid secretion by parietal cells in the stomach;
cardiac stimulant effect; reduce histamine release from
mast cellsa negative feedback effect; activation of
adenylyl cyclase, which increases intracellular cAMP

PROTON PUMP INHIBITORS (PPIs)

Omeprazole, esomeprazole, lansoprazole, pantoprazole,
rabeprazole
MOA: irreversibly inactivate the parietal cell H+/K+ ATPase, the
transporter that is primarily responsible for producing stomach
acid
Lipophilic, enteric coated, duration of action 24 hours
3 to 4 days treatment for full effect
more effective than H2 antagonists for GERD and peptic ulcer
and equally effective in the treatment of nonulcer dyspepsia and
the prevention of stress-related mucosal bleeding
Useful in Zollinger-Ellison syndrome

Mucosal protective agents

Sucralfate (aluminum sucrose sulfate)
small, poorly soluble molecule that polymerizes in the acid environment of
the stomach binds to injured tissue protective coating over ulcer beds
accelerates the healing of peptic ulcers and reduces the recurrence rate
Taken 4 times daily; toxicity is very low (oral route)

Misoprostol (analog of prostaglandin E1)

Increases mucosal protection and inhibits acid secretion; reduce risk of
ulcers from NSAIDs; CHAPTER 18

Colloidal bismuth
ACTIONS: 1) formation of a protective coating on ulcerated tissue, 2)
stimulation of mucosal protective mechanisms, 3) direct antimicrobial
effects, and 4)sequestration of enterotoxins
Bismuth subsalicylate - Reduces stool frequency and liquidity in infectious
diarrhea

ANTIBIOTICS
Chronic infection with H pylori is present in most
patients with recurrent non-NSAID-induced peptic
ulcers.
Eradication of this organism greatly reduces the rate of
recurrence of ulcer in these patients.
One regimen of choice consists of a proton pump
inhibitor plus a course of clarithromycin and amoxicillin
(or metronidazole in patients with penicillin allergy).

Fashner, et.al. 2015 (Am Fam Physician.2015Feb15;91(4):236-242)

Simethicone
Anti-flatulence drug
provide defoaming action in the GI tract
By producing a film in the intestines, simethicone
disperses mucus-enclosed gas pockets and helps
prevent their formation.

Drugs That Promote Upper GI Motility

helpful for gastroparesis and for postsurgical gastric emptying delay;
GERD
Bethanechol (old school)
Neostigmine (acetylcholinesterase inhibitor)
treatment of hospitalized patients with acute large bowel distention (ex: spinal
injury)

Erythromycin motilin receptors; gastroparesis

Metoclopramide and domperidone
D2 dopamine receptor antagonists that promote gastrointestinal motility.
The
action in the area postrema prevent emesis after surgical anesthesia and
emesis induced by cancer chemotherapeutic drugs (CHECKLIST)
metoclopramide can cause symptoms of parkinsonism, other
extrapyramidal effects, and hyperprolactinemia. (CHECKLIST)

Laxatives
increase the probability of a bowel movement by
several mechanisms:
an irritant or stimulant action on the bowel wall;
a bulk-forming action on the stool that evokes reflex
contraction of the bowel;
a softening action on hard or impacted stool;
a lubricating action that eases passage of stool through the
rectum

TABLE 59-1

Anti-diarrheal Agents
opioids and derivatives of opioids that have been selected for
maximal antidiarrheal and minimal CNS effect
diphenoxylate and loperamide
meperidine analogs with very weak analgesic effects.
Diphenoxylate is formulated with antimuscarinic alkaloids (eg, atropine)
to reduce the likelihood of abuse

Kaolin, a naturally occurring hydrated magnesium aluminum

silicate, is combined with pectin, an indigestible carbohydrate
derived from apples in a popular nonprescription preparation that
absorbs bacterial toxins and fluid, resulting in decreased stool
liquidity. They can cause constipation and interfere with
absorption of other drugs.

Drugs Used for Irritable Bowel

Syndrome
IBS is associated with relapsing episodes of
abdominal discomfort (pain, bloating, distention, or cramps) plus
diarrhea or constipation (or both).

Pharmacologic strategy is tailored to patients symptoms

and includes
antidiarrheal agents
laxatives, and
for the treatment of abdominal pain, low doses of tricyclic
antidepressants (Chapter 30); involves blocking 5-HT transporters

Drugs Used for Irritable Bowel

Syndrome
dicyclomine and hyoscyamine (anticholinergics)
used as antispasmodics to relieve abdominal pain
efficacy has not been convincingly demonstrated.
Alosetron, (potent 5-HT3 antagonist),
approved for treatment of women with severe IBS with diarrhea.
can cause constipation, including rare complications of severe constipation that
have required hospitalization or surgery, and rare cases of ischemic colitis.
Lubiprostone
a laxative that activates the type 2 chloride channels in the small intestine, is
approved for treatment of women with IBS with predominant constipation.

Drugs With Antiemetic Actions

(CHECKLIST)
1. Metoclopramide and other D2 dopamine receptor antagonists
2. H1 histamine blocking activity (Chapter 16), including diphenhydramine and
several phenothiazines (Chapter 29 block D2 & 5-HT2 receptors);
3. antimuscarinic drugs such as scopolamine (motion sickness) (Chapter 8);
4. corticosteroid dexamethasone (Chapter 39);
5. cannabinoid receptor agonists dronabinol and nabilone (Chapter 32).
6. 5-HT3 antagonists (ondansetron, granisetron, dolasetron, and palonosetron)
are particularly useful in preventing nausea and vomiting after general
anesthesia and in patients receiving cancer chemotherapy.
7. Aprepitant a newer antiemetic is an antagonist of the neurokinin 1 (NK1)
receptor, a receptor in the area postrema of the CNS that is activated by
substance P and other tachykinins (see Chapter 17).

AMINOSALICYLATES
Drugs containing 5-aminosalicylic acid
(5-ASA or mesalamine) are used as
topical therapy for IBD
MOA: may involve inhibiting the synthesis
of prostaglandins and inflammatory
leukotrienes, and interfering with the
production of inflammatory cytokines
Proprietary formulations of 5-ASA
(Pentasa, Asacol, Lialda) deliver 5-ASA to
different segments of the small and large
intestine
Sulfasalazine (a combination of 5-ASA
and sulfapyridine) has a higher incidence
of adverse effects that the other 5-ASA
drugs, due to the systemic absorption of
the sulfapyridine moiety (nausea, GI
upset, headaches, arthralgias, myalgias,
bone marrow suppression, malaise, and
severe hypersensitivity rxn)

Drugs Used in IBD

Drugs for IBD: Other agents

antibiotics
glucocorticoids (Chapters 39 and 55)
Anti-inflammatory effects: induced synthesis of an inhibitor of
phospholipase A2, decreased mRNA for cyclo oxygenase 2 (COX-2),
decreases in interleukin-2 (IL-2) and IL-3, and decreases in platelet
activating factor (PAF), an inflammatory cytokine.

Immunosuppressive antimetabolites (eg, azathioprine, 6mercaptopurine, methotrexate; Chapters 54 and 55)

anti-tumor necrosis factor [TNF] drugs (eg, infliximab,
Chapters 36 and 55)
Natalizumab

Other Drugs
Drugs for Treating Obesity
Phentermine and sibutramine appetite suppressants
increase the amount of norepinephrine and dopamine in the
brain

Orlistat
binds to gastric and pancreatic lipases in the GI tract

Emetic
Ipecac syrup controversial use for poison treatment

DRUGS USED IN THE

TREATMENT OF
HYPERLIPIDEMIAS
READING ASSIGNMENT

 Atherosclerosis is the leading cause of death in the Western world.

Drugs discussed in this chapter prevent the sequelae of atherosclerosis (heart attacks,
angina, peripheral arterial disease, ischemic stroke) and decrease mortality in patients
with a history of cardiovascular disease and hyperlipidemia.
Although the drugs are generally safe and effective, they can cause problems,
including drug-drug interactions and toxic reactions in skeletal muscle and the liver.

HYPERLIPOPROTEINEMIA
PATHOGENESIS
Premature or accelerated development of atherosclerosis is strongly associated
with elevated concentrations of certain plasma lipoproteins, especially the lowdensity lipoproteins (LDLs) that participate in cholesterol transport.
A depressed level of HDLs is also associated with increased risk of atherosclerosis.
In some families, hypertriglyceridemia is similarly correlated with atherosclerosis.
Chylomicronemia, the occurrence of chylomicrons in the serum while fasting, is a
recessive trait that is correlated with a high incidence of acute pancreatitis and
managed by restriction of total fat intake (Table 351).
Regulation of plasma lipoprotein levels involves a complex interplay of dietary fat
intake, hepatic processing, and utilization in peripheral tissues (Figure 351).
Primary disturbances in regulation occur in a number of genetic conditions
involving mutations in apolipoproteins, their receptors, transport mechanisms,
and lipid-metabolizing enzymes.
Secondary disturbances are associated with a Western diet, many endocrine
conditions, and diseases of the liver or kidneys.

Treatment Strategies
1. DietCholesterol and saturated
fats are the primary dietary factors
that contribute to elevated levels of
plasma lipoproteins.
Dietary measures designed to
reduce the total intake of these
substances constitute the first
method of management and may be
sufficient to reduce lipoprotein
levels to a safe range.
Because alcohol raises triglyceride
and VLDL levels, it should be
avoided by patients with
hypertriglyceridemia.

2. Drugs tailored choice of drug treatment is based on the lipid

abnormality. (Table 352)

most effective at lowering LDL cholesterol include:

HMG-CoA reductase inhibitors

Resins
Ezetimibe
niacin.

most effective at lowering triglyceride and VLDL concentrations and

raising HDL cholesterol concentrations:

Fibric acid derivatives (eg,

gemfibrozil)
niacin
marine omega-3 fatty acids