Lippincott Important Recalls > Chapter 31: GI & Antiemetic Drugs > Flashcards
Chapter 31: GI & Antiemetic Drugs Flashcards
ANTIMICROBIAL AGENTS
Amoxicillin AMOXIL, TRIMOX
Bismuth compounds PEPTO-BISMOL,
KAOPECTATE
Clarithromycin BIAXIN
Metronidazole FLAGYL
Tetracycline SUMYCIN
H2 receptor blockers
Cimetidine TAGAMET
Famotidine PEPCID
Nizatidine AXID
Ranitidine ZANTAC
PPI
Dexlansoprazole DEXILANT
Esomeprazole NEXIUM
Lansoprazole PREVACID
Omeprazole PRILOSEC
Pantoprazole PROTONIX
Rabeprazole ACIPHE
Prostaglandin
Misoprostol
ANTIMUSCARINIC AGENTS
Dicyclomine
Antacids
Aluminum hydroxide ALTERNAGEL
Calcium carbonate TUMS
Magnesium hydroxide MILK OF MAGNESIA
Sodium bicarbonate NUMEROUS
Mucosal protective agents
Bismuth subsalicylate PEPTO-BISMOL
Sucralfate CARAFATE
Phenothiazine
Prochlorperazine COMPAZINE
5-HT3 SEROTONIN RECEPTOR
BLOCKERS
5-HT3 SEROTONIN RECEPTOR
BLOCKERS
Dolasetron ANZEMET
Granisetron KYTRIL
Ondansetron ZOFRAN
Palonosetron ALOX
SUBSTITUTED BENZAMIDES
Metoclopramide
BUTYROPHENONES
BUTYROPHENONES
Droperidol
Haloperidol HALDOL
BENZODIAZEPINES
BENZODIAZEPINES
Alprazolam XANAX
Lorazepam ATIVAN
CORTICOSTEROIDS
CORTICOSTEROIDS
Dexamethasone DECADRON
Methylprednisolone MEDROL
SUBSTANCE P/NEUROKININ-1
RECEPTOR BLOCKER
SUBSTANCE P/NEUROKININ-1
RECEPTOR BLOCKER
Aprepitant EMEND
ANTIMOTILITY AGENTS
ANTIMOTILITY AGENTS
Diphenoxylate + atropine LOMOTIL
Loperamide IMODIUM A-D
ADSORBENTS
ADSORBENTS
Aluminum hydroxide ALTERNAGEL
Methylcellulose CITRUCEL
AGENTS THAT MODIFY FLUID AND
ELECTROLYTE TRANSPORT
AGENTS THAT MODIFY FLUID AND
ELECTROLYTE TRANSPORT
Bismuth subsalicylate PEPTO-BISMOL
BULK LAXATIVES
BULK LAXATIVES
Methylcellulose CITRUCEL
Psyllium METAMUCIL, FIBERAL
SALINE and OSMOTIC LAXATIVES
SALINE and OSMOTIC LAXATIVES
Magnesium citrate CITROMA
Magnesium hydroxide MILK OF MAGNESIA
Polyethylene glycol MIRALAX, GOLYTELY,
MOVIPREP, NULYTELY, TRILYTE
Lactulose CONSTULOSE, ENULOSE, GENER-
LAC, KRISTALOSE
Stool softeners
Docusate COLACE, DOCU-SOFT
Lubricant laxatives
Glycerin suppositories
Mineral oil
CHLORIDE CHANNEL ACTIVATORS
Lubiprostone AMITIZA
Lubiprostone AMITIZA
PPI
PPIs: Inhibitors of the H+/K+-ATPase proton pump
The PPIs bind to the H+/K+-ATPase enzyme system (proton pump)
and suppress the secretion of hydrogen ions into the gastric lumen.
The membrane-bound proton pump is the final step in the secretion
of gastric acid (Figure 31.4). The available PPIs include dexlanso-
prazole [DEX-lan-SO-pra-zole], esomeprazole [es-oh-MEH-pra-zole],
lansoprazole [lan-SO-pra-zole], omeprazole [oh-MEH-pra-zole], pan-
toprazole [pan-TOE-pra-zole], and rabeprazole [rah-BEH-pra-zole].
Omeprazole, esomeprazole, and lansoprazole are available over-the-
counter for short-term treatment of GERD.
1. Actions: These agents are prodrugs with an acid-resistant
enteric coating to protect them from premature degradation by
gastric acid. The coating is removed in the alkaline duodenum,
and the prodrug, a weak base, is absorbed and transported to the
parietal cell. There, it is converted to the active drug and forms a
stable covalent bond with the H+/K+-ATPase enzyme. It takes about
18 hours for the enzyme to be resynthesized, and acid secretion
is inhibited during this time. At standard doses, PPIs inhibit both
basal and stimulated gastric acid secretion by more than 90%. An
oral product containing omeprazole combined with sodium bicar-
bonate for faster absorption is also available over the counter and
by prescription.
2. Therapeutic uses: The PPIs are superior to the H2
antagonists in
suppressing acid production and healing ulcers. Thus, they are the
preferred drugs for stress ulcer treatment and prophylaxis and for
the treatment of GERD, erosive esophagitis, active duodenal ulcer,
and pathologic hypersecretory conditions (for example, Zollinger-
Ellison syndrome, in which a gastrin-producing tumor causes
hypersecretion of HCl). If a once-daily PPI is only partially effective
for GERD symptoms, increasing dosing to twice daily or adminis-
tering the PPI in the morning and adding an H2
antagonist in the
evening may improve symptom control. If an H2
-receptor antago-
nist is needed, it should be taken well after the PPI. H2
antagonists
reduce the activity of the proton pump, and PPIs require active
pumps to be effective. PPIs also reduce the risk of bleeding from
ulcers caused by aspirin and other NSAIDs and may be used for
prevention or treatment of NSAID-induced ulcers. Finally, they are
used with antimicrobial regimens to eradicate H. pylori.
3. Pharmacokinetics: All of these agents are effective orally. For
maximum effect, PPIs should be taken 30 to 60 minutes before
breakfast or the largest meal of the day. [Note: dexlansoprazole
has a dual delayed release formulation and can be taken with-
out regard to food.] Esomeprazole, lansoprazole, and pantopra-
zole are also available in intravenous formulations. Although the
plasma half-life of these agents is only a few hours, they have a
long duration of action due to covalent bonding with the H+/K+-
ATPase enzyme. Metabolites of these agents are excreted in urine
and feces.
4. Adverse effects: The PPIs are generally well tolerated.
Omeprazole and esomeprazole may decrease the effective-
ness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite. Although
the effect on clinical outcomes is questionable, concomitant use
of these PPIs with clopidogrel is not recommended because of
a possible increased risk of cardiovascular events. PPIs may
increase the risk of fractures, particularly if the duration of use is
1 year or greater (Figure 31.6). Prolonged acid suppression with
PPIs (and H2
antagonists) may result in low vitamin B12 because
acid is required for its absorption in a complex with intrinsic fac-
tor. Elevated gastric pH may also impair the absorption of calcium
carbonate. Calcium citrate is an effective option for calcium supple-
mentation in patients on acid suppressive therapy, since absorp-
tion of the citrate salt is not affected by gastric pH. Diarrhea and
Clostridium difficile colitis may occur in community patients receiv-
ing PPIs. Patients must be counseled to discontinue PPI therapy
and contact their physician if they have diarrhea for several days.
Additional adverse effects may include hypomagnesemia and an
increased incidence of pneumonia.
Prostaglandin
Prostaglandins
Prostaglandin E, produced by the gastric mucosa, inhibits secretion
of acid and stimulates secretion of mucus and bicarbonate (cytopro-
tective effect). A deficiency of prostaglandins is thought to be involved
in the pathogenesis of peptic ulcers. Misoprostol [mye-soe-PROST-
ole], an analog of prostaglandin E1
, is approved for the prevention
of NSAID-induced gastric ulcers (Figure 31.7). Prophylactic use of
misoprostol should be considered in patients who are taking NSAIDs
and are at moderate to high risk of NSAID-induced ulcers, such as
elderly patients and those with previous ulcers. Misoprostol is contra-
indicated in pregnancy, since it can stimulate uterine contractions and
cause miscarriage. Dose-related diarrhea and nausea are the most
common adverse effects and limit the use of this agent. Thus, PPIs
are preferred agents for the prevention of NSAID-induced ulcers.
Antacids
Antacids
Antacids are weak bases that react with gastric acid to form water
and a salt to diminish gastric acidity. Because pepsin (a proteolytic
enzyme) is inactive at a pH greater than 4, antacids also reduce pep-
sin activity.
1. Chemistry: Antacid products vary widely in their chemical com-
position, acid-neutralizing capacity, sodium content, palatability,
and price. The efficacy of an antacid depends on its capacity to
neutralize gastric HCl and on whether the stomach is full or empty
(food delays stomach emptying allowing more time for the antacid
to react). Commonly used antacids are combinations of salts of
aluminum and magnesium, such as aluminum hydroxide and mag-
nesium hydroxide [Mg(OH)2
]. Calcium carbonate [CaCO3
] reacts
with HCl to form CO2
and CaCl2
and is also a commonly used
preparation. Systemic absorption of sodium bicarbonate [NaHCO3
]
can produce transient metabolic alkalosis. Therefore, this antacid
is not recommended for long-term use.
2. Therapeutic uses: Antacids are used for symptomatic relief
of peptic ulcer disease and GERD, and healing of duodenal ulcers. They should be administered after
meals for maximum effectiveness. [Note: Calcium carbonate prep-
arations are also used as calcium supplements for the treatment
of osteoporosis.]
3. Adverse effects: Aluminum hydroxide tends to cause constipa-
tion, whereas magnesium hydroxide tends to produce diarrhea.
Preparations that combine these agents aid in normalizing bowel
function. Absorption of the cations from antacids (Mg2+, Al3+, Ca2+)
is usually not a problem in patients with normal renal function;
however, accumulation and adverse effects may occur in patients
with renal impairment.
Adverse effects: Aluminum hydroxide tends to cause constipa-
tion, whereas magnesium hydroxide tends to produce diarrhea.
Preparations that combine these agents aid in normalizing bowel
function. Absorption of the cations from antacids (Mg2+, Al3+, Ca2+)
is usually not a problem in patients with normal renal function;
however, accumulation and adverse effects may occur in patients
with renal impairment.
Sucralfate
Sucralfate: This complex of aluminum hydroxide and sulfated
sucrose binds to positively charged groups in proteins of both
normal and necrotic mucosa. By forming complex gels with epi-
thelial cells, sucralfate [soo-KRAL-fate] creates a physical barrier
that protects the ulcer from pepsin and acid, allowing the ulcer to
heal. Although sucralfate is effective for the treatment of duodenal
ulcers and prevention of stress ulcers, its use is limited due to the
need for multiple daily dosing and drug–drug interactions. Because
it requires an acidic pH for activation, sucralfate should not be
administered with PPIs, H2
antagonists, or antacids. Sucralfate is
well tolerated, but it can interfere with the absorption of other drugs
by binding to them. This agent does not prevent NSAID-induced
ulcers, and it does not heal gastric ulcers.
Bismuth subsalicylate
Bismuth subsalicylate: This agent is used as a component of
quadruple therapy to heal peptic ulcers. In addition to its antimicro-
bial actions, it inhibits the activity of pepsin, increases secretion of
mucus, and interacts with glycoproteins in necrotic mucosal tissue
to coat and protect the ulcer.
Phenothiazine
. Phenothiazines: The first group of drugs shown to be effective
antiemetic agents, phenothiazines, such as prochlorperazine
[proe-klor-PER-ah-zeen], act by blocking dopamine receptors.
Prochlorperazine is effective against low or moderately emeto-
genic chemotherapeutic agents (for example, fluorouracil and
doxorubicin). Although increasing the dose improves antiemetic
activity, side effects are dose limiting.
5HT3 receptor blockers
5-HT3
receptor blockers: The 5-HT3
receptor antagonists
include ondansetron [on-DAN-seh-tron], granisetron [gra-NI-seh-
tron], palonosetron [pa-low-NO-seh-tron], and dolasetron [dol-A-
seh-tron]. These agents selectively block 5-HT3
receptors in the
periphery (visceral vagal afferent fibers) and in the brain (CTZ).This class of agents is important in treating emesis linked with
chemotherapy, largely because of their longer duration of action
and superior efficacy. These drugs can be administered as a sin-
gle dose prior to chemotherapy (intravenously or orally) and are
efficacious against all grades of emetogenic therapy. Ondansetron
and granisetron prevent emesis in 50% to 60% of cisplatin-treated
patients. These agents are also useful in the management of post-
operative nausea and vomiting. 5-HT3
antagonists are extensively
metabolized by the liver; however, only ondansetron requires dos-
age adjustments in hepatic insufficiency. Elimination is through the
urine. Electrocardiographic changes, such as a prolonged QTc
interval, can occur with dolasetron and high doses of ondanse-
tron. For this reason, dolasetron is no longer approved for CINV
prophylaxis.
Substituted benzamides
Substituted benzamides: One of several substituted benzamides
with antiemetic activity, metoclopramide [met-oh-kloe-PRAH-mide]
is effective at high doses against the emetogenic cisplatin, prevent-
ing emesis in 30% to 40% of patients and reducing emesis in the
majority of patients. Metoclopramide accomplishes this through
inhibition of dopamine in the CTZ. Antidopaminergic side effects,
including extrapyramidal symptoms, limit long-term high-dose use.
Metoclopramide was previously used as a prokinetic drug for the
treatment of GERD. However, due to the adverse effect profile and
the availability of more effective drugs, such as PPIs, it should be
reserved for patients with documented gastroparesis
Butyrophenones
Butyrophenones: Droperidol [droe-PER-i-doll] and haloperidol
[hal-oh-PER-i-doll] act by blocking dopamine receptors. The butyr-
ophenones are moderately effective antiemetics. Droperidol had
been used most often for sedation in endoscopy and surgery, usu-
ally in combination with opioids or benzodiazepines. However, it
may prolong the QTc
interval and should be reserved for patients
with inadequate response to other agents. High-dose haloperidol
was found to be nearly as effective as high-dose metoclopramide
in preventing cisplatin-induced emesis.
Benzodiazepines
Benzodiazepines: The antiemetic potency of lorazepam [lor-A-
ze-pam] and alprazolam [al-PRAH-zoe-lam] is low. Their beneficial
effects may be due to their sedative, anxiolytic, and amnesic prop-
erties. These same properties make benzodiazepines useful in
treating anticipatory vomiting. Concomitant use of alcohol should
be avoided due to additive CNS depressant effects.
Corticosteroid
Corticosteroids: Dexamethasone [dex-a-MEH-tha-sone] and
methylprednisolone [meth-ill-pred-NIH-so-lone], used alone, are
effective against mildly to moderately emetogenic chemotherapy.
Most frequently, however, they are used in combination with other
agents. Their antiemetic mechanism is not known, but it may
involve blockade of prostaglandins.
Substance P/neurokinin-1 receptor blocker:
Substance P/neurokinin-1 receptor blocker: Aprepitant [ah-
PRE-pih-tant] targets the neurokinin receptor in the brain and
blocks the actions of the natural substance. Aprepitant is indicated
only for highly or moderately emetogenic chemotherapy regi-
mens. It is usually administered orally with dexamethasone and a 5-HT3
antagonist. It undergoes extensive metabolism, primar-
ily by CYP3A4, and it may affect the metabolism of other drugs
that are metabolized by this enzyme, such as warfarin and oral
contraceptives.
Antimotility
Antimotility agents
Two drugs that are widely used to control diarrhea are diphenoxylate
[dye-fen-OX-see-late] and loperamide [loe-PER-ah-mide]. Both are
analogs of meperidine and have opioid-like actions on the gut. They
activate presynaptic opioid receptors in the enteric nervous system
to inhibit acetylcholine release and decrease peristalsis. At the usual
doses, they lack analgesic effects. Because these drugs can contrib-
ute to toxic megacolon, they should not be used in young children or
in patients with severe colitis.
Adsorbents
Adsorbents
Adsorbent agents, such as aluminum hydroxide and methylcellulose
[meth-ill-CELL-you-lowse], are used to control diarrhea. Presumably,
these agents act by adsorbing intestinal toxins or microorganisms
and/or by coating or protecting the intestinal mucosa. They are much
less effective than antimotility agents, and they can interfere with the
absorption of other drugs.
Agents that modify fluid and electrolyte transport
Agents that modify fluid and electrolyte transport
Bismuth subsalicylate, used for traveler’s diarrhea, decreases fluid
secretion in the bowel. Its action may be due to its salicylate compo-
nent as well as its coating action. Adverse effects may include black
tongue and black stools.
Senna
Senna: This agent is a widely used stimulant laxative. Its active
ingredient is a group of sennosides, a natural complex of anthra-
quinone glycosides. Taken orally, senna causes evacuation of the
bowels within 8 to 10 hours. It also causes water and electrolyte
secretion into the bowel. In combination products with a docusate-
containing stool softener, it is useful in treating opioid-induced
constipation.
Bisacodyl
Bisacodyl: Available as suppositories and enteric-coated tablets,
bisacodyl is a potent stimulant of the colon. It acts directly on nerve
fibers in the mucosa of the colon.
Castor oil
Castor oil: This agent is broken down in the small intestine to
ricinoleic acid, which is very irritating to the stomach and promptly
increases peristalsis. Pregnant patients should avoid castor oil
because it may stimulate uterine contractions.
Bulk laxatives
Bulk laxatives
The bulk laxatives include hydrophilic colloids (from indigestible
parts of fruits and vegetables). They form gels in the large intestine,
causing water retention and intestinal distension, thereby increasing
peristaltic activity. Similar actions are produced by methylcellulose,
psyllium seeds, and bran. They should be used cautiously in patients
who are immobile because of their potential for causing intestinal
obstruction
Saline & osmotic laxatives
Saline and osmotic laxatives
Saline cathartics, such as magnesium citrate and magnesium
hydroxide, are nonabsorbable salts (anions and cations) that hold
water in the intestine by osmosis. This distends the bowel, increasing
intestinal activity and producing defecation in a few hours. Electrolyte
solutions containing polyethylene glycol (PEG) are used as colonic
lavage solutions to prepare the gut for radiologic or endoscopic pro-
cedures. PEG powder for solution is available as a prescription and
also as an over-the-counter laxative and has been shown to cause
less cramping and gas than other laxatives. Lactulose is a semisyn-
thetic disaccharide sugar that acts as an osmotic laxative. It can-
not be hydrolyzed by GI enzymes. Oral doses reach the colon and
are degraded by colonic bacteria into lactic, formic, and acetic acids.
This increases osmotic pressure, causing fluid accumulation, colon
distension, soft stools, and defecation. Lactulose is also used for
the treatment of hepatic encephalopathy, due to its ability to reduce
ammonia levels.
Stool softeners
Stool softeners (emollient laxatives or surfactants)
Surface-active agents that become emulsified with the stool produce
softer feces and ease passage. These include docusate sodium and docusate calcium. They may take days to become effective and are
often used for prophylaxis rather than acute treatment. Stool soften-
ers should not be taken concomitantly with mineral oil because of the
potential for absorption of the mineral oil.
Lubricant laxatives
Lubricant laxatives
Mineral oil and glycerin suppositories are lubricants and act by facili-
tating the passage of hard stools. Mineral oil should be taken orally
in an upright position to avoid its aspiration and potential for lipid or
lipoid pneumonia.
Chloride channel activators
Chloride channel activators
Lubiprostone [loo-bee-PROS-tone], currently the only agent in this
class, works by activating chloride channels to increase fluid secre-
tion in the intestinal lumen. This eases the passage of stools and
causes little change in electrolyte balance. Lubiprostone is used in
the treatment of chronic constipation, particularly because tolerance
or dependency has not been associated with this drug. Also, drug–
drug interactions appear minimal because metabolism occurs quickly
in the stomach and jejunum.
