Transcript PowerPoint_Chapter15x - EMC Paradigm Internet Resource

Chapter 15
The Gastrointestinal System
and Drug Therapy
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Chapter 15
Topics
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Anatomy and Physiology of the GI System
Diarrhea
Constipation
Heartburn and Ulcers
Nausea and Vomiting
Hemorrhoids
Other GI Conditions
Herbal and Alternative Therapies
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Anatomy and Physiology of the GI System
GI Tract
• GI tract has two systems:
the upper GI system (the
mouth, esophagus, and
stomach) and the lower
GI system (the intestines,
colon, and rectum)
• Some organs in the GI
system play a major role
in the pharmacokinetic
process.
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Anatomy and Physiology of the GI System
About the GI System
• The GI system processes food and liquids in two ways
 Digestion: the breakdown of large food molecules to
smaller ones
 Absorption: uptake of essential nutrients into the
bloodstream
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Anatomy and Physiology of the GI System
Process of Digestion
• Food moves down the esophagus to the stomach
• In the stomach
 Ingested food triggers the release of gastrin (hormone)
 Stimulates histamine release which increases the
number of active proton pumps
 Stimulates acid production from proton pumps
 Acid and enzyme secretions digest large particles
• Acidic stomach environment (pH: 1 to 2) helps digest food,
kills ingested bacteria, and is critical for absorption of
certain drugs
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Anatomy and Physiology of the GI System
Process of Absorption
• From stomach, food particles enter small intestine, where
 Most digestion and nutrient absorption takes place due
to large surface area
 Most oral drugs are absorbed systemically
• Remaining food particles move to large intestine, where
 Useful substances such as salt and water are absorbed
 Nonabsorbable substances (fiber, bacteria) are
eliminated as waste (stool) through the rectum and
anus
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Anatomy and Physiology of the GI System
Movement of Ingested Food
• Peristalsis (process of coordinated muscle contraction)
moves food particles through the GI tract
 In intestines, process called GI motility
• Sphincters regulate the speed at which the food particles
move through the tract
 These muscle rings prevent digested substances from
moving in the wrong direction
• The closing of the lower esophageal sphincter, located
between the esophagus and stomach, keeps stomach
acid from traveling up the esophagus
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Anatomy and Physiology of the GI System
Other Components of the GI System
• Other organs of the GI system include the salivary glands,
gallbladder, pancreas, and liver
• These organs release secretions that aid in digestion of
food and absorption of nutrients
 The salivary glands produce saliva that helps digest
sugars in food and allows for easier swallowing
 The gallbladder stores bile, a fluid produced by the liver
that aids the absorption of fat and cholesterol from the
small intestine
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Anatomy and Physiology of the GI System
Pancreas
• Pancreatic
secretions aid in
the digestion of
carbohydrates,
proteins, and fats
and neutralize
stomach acid
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Anatomy and Physiology of the GI System
Liver
• The liver is the major organ for metabolism of harmful
substances and orally administered drugs
• Because blood flow from the GI system goes through the
liver before entering the body’s circulation, many drugs
undergo the first-pass effect
 First-pass effect: the metabolism of drugs by the liver
before they reach their target in the body
 Result of first-pass effect: full drug dose does not reach
the body
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Anatomy and Physiology of the GI System
Liver Function
and First-Pass
Effect
• Alternatives to oral
administration are
necessary for drugs
that will lose their
efficacy if they
undergo the firstpass effect
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Diarrhea
About Diarrhea
• Diarrhea is excessive, soft, or watery stools
 Excessive can mean large stool volume or more bowel
movements than normal (due to increased GI motility)
• Two types of diarrhea: acute and chronic
 Acute diarrhea is common; caused by infections, food
poisoning, drugs (see Table 15.1)
 Infectious causes: bacterial (E. coli, salmonella);
protozoal (giardia); viral (Norwalk, rotavirus)
 Chronic diarrhea is less common; causes are IBS,
ulcerative colitis, or Crohn’s disease
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Diarrhea
Drugs for Diarrhea
• Antidiarrheal medications treat symptoms; slow transit of
food through the GI tract or decrease secretions into it
 This reduces stool volume and makes stool less watery
• Diarrhea is a symptom of a disease, not a disease itself
 Medications reduce symptoms but do not treat the
underlying disease
• Antibiotics are used for diarrhea caused by bacterial
infection; fluid or electrolyte replacement may be needed
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Diarrhea
Drugs for Diarrhea: Opiate Derivatives
• Indication: short-term relief of acute diarrhea
• Mechanism of Action: inhibit peristalsis; reduce liquid
content of stool
• Route: all are oral
• Side Effects (common): dizziness, drowsiness
• Side Effects (atropine): blurred vision, dry mouth, difficulty
urinating
• Cautions: diphenoxylate is scheduled (C-V); requires
special storage and handling
• Caution: seldom used for children under age 2
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Diarrhea
Drugs for Diarrhea: Bismuth Subsalicylate
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Indications: acute diarrhea, traveler’s diarrhea
Indication (other): H. pylori infection
Mechanism of Action: makes stools less watery
Route: oral; available OTC
Side Effects (common): constipation, nausea, vomiting,
darkening of tongue and/or stools (temporary, harmless)
• Side Effects (severe, rare): tinnitus, confusion, weakness
• Cautions: should not be used in patients with aspirin
hypersensitivity; typically not given to children/teens
• Caution: should not be taken with tetracycline antibiotics
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Constipation
About Constipation
• Constipation is characterized by infrequent bowel
movements, small stool size, hard stools, or the feeling of
incomplete bowel evacuation
• Causes of constipation include
 Diet low in fiber or fluid intake
 Certain foods or drugs, particularly pain medicines such
as opiates and antacids
• Dietary and lifestyle changes with drug therapy help
 Drink plenty of fluids, eat adequate fiber,
and exercise regularly
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Constipation
Drugs for Constipation
• Indication (laxatives): only as needed short-term
 Electrolyte abnormalities can occur if taken often
• Routes: all are oral; some rectal (suppositories or enemas)
• Rectal suppositories or enemas are used for rapid
treatment of moderate to severe constipation and in
hospitalized patients unable to swallow
 Rectal suppositories are inserted into rectum; take
15-60 minutes to work
 Enemas are solutions delivered directly into
rectum
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Constipation
Suppository
Insertion
• Patient should
remove the foil
wrapping of the
suppository and
insert the pointed
end into the rectum.
• Insertion should be
far enough into the
rectum to avoid
release
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Constipation
Drugs for Constipation: Enemas
• Enemas are solutions that are delivered into rectum
• Indications: rapidly clear out the bowels prior to surgery
or diagnostic procedures, such as colonoscopy; remove
excessive fecal matter blocking the GI tract
• Patient should insert enema tip into the rectum, squeeze
the bottle or allow liquid to drain via gravity, hold liquid in
rectum 2 to 60 minutes, then defecate
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Constipation
Drugs for Constipation: Bulk-Forming Laxatives
• Indications: mild constipation; constipation prevention
 Use daily for regular bowel movements
• Mechanism of Action: draw water and other electrolytes
into GI system; facilitate bowel movements; absorb fat and
reduce glucose (beneficial for patients with diabetes or
high cholesterol)
• Side Effects (rare): obstruction of the esophagus or bowels
• Caution: avoid in patients with intestinal stenosis
• Caution: can affect drug absorption; separate doses from
other medications by at least 2 hours
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Constipation
Drugs for Constipation: Stool Softeners
• Indication: for patients at risk of becoming constipated
• Mechanism of Action: increase water and electrolyte
secretions in GI tract; make stools softer, easier to pass
• Routes: all are oral; some are also rectal
• Side Effects: throat irritation, abdominal pain, diarrhea,
intestinal obstruction
• Caution: Excessive or long-term use may lead to electrolyte
imbalance
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Constipation
Drugs for Constipation: Stimulant Laxatives
• Indications: acute constipation, use only as needed shortterm; often used to treat opiate-induced constipation
• Mechanism of Action: stimulate parasympathetic neurons
that control bowel muscles, enhancing peristalsis and GI
motility
• Side Effects (common): mild abdominal pain, nausea,
vomiting, rectal burning
• Caution: do not take with dairy products and antacids
• Caution (senna): contraindicated in patients with intestinal
obstruction, Crohn’s disease, abdominal pain, pregnancy
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Constipation
Drugs for Constipation: Bowel Prep Laxatives
• Indications: evacuation of bowels before surgery or
diagnostic procedure; clearing poisons or parasitic worms
from GI tract; treatment of bowel impaction
• Mechanism of Action: draw water and electrolytes into the
GI tract; completely clean out GI tract
• Routes: oral and rectal; some available only by prescription
• Side Effects (common): abdominal pain, diarrhea,
electrolyte loss or imbalance
• Cautions: occasional use only; use with caution in patients
with kidney problems and children under age 2
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Constipation
Drugs for Constipation: Miscellaneous
Laxatives
• Milk of magnesia
 Indication: mild constipation; common OTC product
 Route: oral; liquid and chewable tablet forms
• Glycerin suppositories
 Indication: occasional constipation in children
• Lactulose
 Indication: ammonia toxicity and delirium in patients
with end-stage liver failure
 Route: oral; solution form
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Your Turn
Question 1: What are two restrictions for using bismuth
subsalicylate?
Answer: This medication should not be taken if a patient has
aspirin hypersensitivity or is taking tetracycline antibiotics.
Question 2: What is the purpose of using enemas?
Answer: They are used to rapidly clear out the bowels prior
to surgery or diagnostic procedures.
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Heartburn and Ulcers
GERD (Heartburn)
• Common complaint; estimated that 10% of people in the
United States get heartburn every week
• Characterized by a burning or sensation of warmth starting
in the gut or chest that may radiate to the neck
• In GERD, the lower esophageal sphincter is faulty, allowing
acidic stomach contents to move up into the esophagus
 Acid reflux causes permanent changes in esophageal
lining; linked to narrowing and cancer of the esophagus
 Long-term treatment reduces acidity of the stomach
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Heartburn and Ulcers
Foods and Medications that May Worsen GERD
Foods
Chocolate
Coffee or soda
Fatty foods
Garlic
Onions
Orange juice
Mint
Spicy foods
Medications
Alcohol
Alendronate
Anticholinergics
Aspirin
Barbiturates
Caffeine
Dopamine
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Iron
Nicotine (from
smoking)
Nitrates
NSAIDs
Tetracycline
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Heartburn and Ulcers
Ulcers
• Sores or patches of dead tissue along
the walls of the GI tract
• They occur when the protective lining of the GI tract is
worn away and bleeding occurs
• The most common cause of ulcers (PUD) is H. pylori, a
bacterial parasite that attaches to lining of the stomach
 Releases toxic chemicals that damage the lining
 Causes damage to cells in stomach and small intestine
• Duodenal ulcers occur in the small intestine just below
the stomach; caused by hyperacidity
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Heartburn and Ulcers
Ulcers (continued)
• Stress ulcers occur in critically ill patients who are
bedridden; mechanism is unknown
• Prolonged use of NSAIDs and aspirin can cause ulcers;
these acidic drugs irritate and erode GI tissue
 They also inhibit production of prostaglandins that
protect the lining of the stomach from acid secretions
 When ulceration erodes into a blood vessel, a GI bleed
can occur
• Long-term NSAID, aspirin, or anticoagulation therapy
leads to high risk for ulcers and life-threatening bleeding
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Heartburn and Ulcers
Drugs for GERD and PUD
• Most treatments do not directly fix GERD or GI ulcers
• Antacids, PPIs, and H2 blockers relieve symptoms of GERD
by decreasing acid production in the stomach
Drugs for GERD and PUD: Antacids
• Indication (short-term): mild to moderate GERD
• Mechanism of Action: contain special ions that react with
hydrogen ions in the stomach and neutralize acid
• Side Effects (common): constipation, diarrhea, stomach
pain, nausea, vomiting
• Caution: do not take at the same time with antibiotics
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Heartburn and Ulcers
Drugs for GERD and PUD: PPIs
• Indications: GERD, PUD, and H. pylori infection
• Mechanism of Action: bind to proton pumps in stomach
lining, inactivating them; work 24 hours
• Routes: all are oral (liquid for infants); some are also IV (for
critically ill patients and those at risk for stress ulcers)
 All prescription; lansoprazole and omeprazole also OTC
• Side Effects (rare): headache, nausea, vomiting, diarrhea
• Cautions: do not crush or chew delayed-release
capsules or tablets ; do not take with digoxin or
ketoconazole
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Heartburn and Ulcers
Drugs for GERD and PUD: H2 Blockers
• Indications: GERD, PUD
• Mechanism of Action: block type 2 histamine receptors in
the stomach by decreasing proton pump activity
• Routes: all oral; most also IV (critically ill in the hospital)
 All OTC; work for 8 hours; take as needed
• Side Effects (common): headache, diarrhea, and dizziness
• Cautions: do not take with digoxin or ketoconazole
• Caution (cimetidine): several drug interactions; patient
should talk with pharmacist before taking
• Caution (ranitidine): avoid in patients with hepatitis
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Heartburn and Ulcers
Drugs for GERD and PUD: Sucralfate
• Indications: in products for infants with GERD
• Mechanism of Action: coats stomach and small intestine
walls, forming a protective barrier against stomach acid
• Take on an empty stomach
• Cautions: interacts with many drugs
Drugs for GERD and PUD: Regimens for H. Pylori
• All multidrug regimens consist of a PPI or an H2 blocker to
heal the ulcer and antibiotics to kill the bacteria in the
GI tract
• Combination products also available
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Nausea and Vomiting
About Nausea and Vomiting
• Nausea and vomiting are related symptoms caused by
various diseases and conditions
 Morning sickness: occurs in early pregnancy; caused by
hormonal changes
 Motion sickness: follows movement; affects balance
• Nausea is the feeling of the need to vomit
• Vomiting (also called emesis) is the expulsion of stomach
contents out of the mouth; involves reverse peristalsis
 Defense mechanism to protect the body from harmful
substances that have been consumed
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Nausea and Vomiting
About Nausea and Vomiting
• All drugs are foreign substances to the body and may
trigger nausea and vomiting, including
 Antibiotics
 Antiseizure medications
 Chemotherapy agents
 Digoxin
 Opiates
 Theophylline
• Radiation treatments can also cause nausea and vomiting
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Nausea and Vomiting
The CTZ
• Blocking receptors for
serotonin, dopamine,
histamine, and
substance P in the CTZ
can relieve symptoms of
nausea and vomiting
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Nausea and Vomiting
Drugs for Nausea and Vomiting:
Anticholinergic Antiemetics
• Indication: mild motion sickness
• Mechanism of Action: block histamine and acetylcholine
(neurotransmitters in the CTZ and vomiting center)
• Routes: all are oral; some are also IM; dimenhydrinate is
available in an IV form; scopolamine is also transdermal
• Side Effects: urinary retention, drowsiness
• Cautions: do not take with alcohol or MAOIs; avoid in
patients with prostate enlargement or glaucoma; do not
give to infants or breast-feeding mothers
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Nausea and Vomiting
Drugs for Nausea and Vomiting: General
Antiemetics
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Used in inpatient settings; mechanism of action varies
Routes: all are oral, IM, and IV; some are also rectal
Side Effects (all, common): drowsiness and sedation
Side Effects (phenothiazines): EPS side effects (tardive
dyskinesia and dystonia)
 Elderly patients must be closely monitored for EPS
• Cautions: sedative effects make driving difficult;
do not take with alcohol
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Nausea and Vomiting
Drugs for Nausea and Vomiting: Serotonin
Type 3 (5-HT3) Receptor Antagonists
• Indication: prevention and treatment of severe nausea and
vomiting from chemotherapy, radiation, or anesthesia
 Potent prescription-only antiemetics
• Mechanism of Action: block serotonin type 3 (5-HT3)
receptors in the brain and GI tract
• Route: all oral and IV; some IM and transdermal patch
• Side Effects (common): headache, fatigue, constipation,
drowsiness, muscle weakness, dizziness
• Caution: sedative effects make driving difficult
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Nausea and Vomiting
Drugs for Nausea and Vomiting: Neurokinin 1
Inhibitor
• Indication: Prevention of nausea and vomiting induced by
chemotherapy drugs or anesthesia
• Mechanism of Action: blocks NK1 receptors, preventing
substance P from stimulating nausea
• Route: oral; only available by prescription
 Aprepitant (Emend) is only one on market
• Side Effects: fatigue, muscle weakness, constipation
• Side Effects (rare, significant): hypotension, kidney and
liver dysfunction, slow heart rate, diarrhea, blood changes
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Your Turn
Question 1: How can you tell if a patient is taking medications to
treat a peptic ulcer caused by H. pylori?
Answer: The patient would be taking a multidrug regimen
that consists of a PPI or an H2 blocker to heal the ulcer and
antibiotics to destroy the bacteria. The patient may also be
taking an antacid.
Question 2: A patient has nausea and vomiting during airplane
rides. At the pharmacy, he asks if a medicine can stop this from
happening. What drug therapy is likely recommended?
Answer: OTC anticholinergic agents can be used to treat mild
nausea and vomiting for a patient who has motion sickness.
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Hemorrhoids
About Hemorrhoids
• Hemorrhoids are blood vessels from the hemorrhoidal
cushion (the area surrounding the anal sphincter) that are
forced into the anal cavity in response to straining during
defecation or passing hard stools
 Similar to varicose veins, except they occur in the blood
vessels near the anus rather than in the legs
• Hemorrhoid disease is bleeding and irritation when a
blood vessel of the hemorrhoidal cushion ruptures
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Hemorrhoids
Drugs for Hemorrhoids
• Medications for hemorrhoids decrease symptoms but do
not reduce bleeding or cure the underlying problem
• Treatment of mild hemorrhoids
 Increase water and fiber intake
 Use topical hemorrhoid agents for itching and pain;
witch hazel (an astringent) may help stop bleeding
 Use pramoxine, a local anesthetic, to treat discomfort
• Treatment of moderate to severe hemorrhoids
 May require topical corticosteroids such as ProctoFoam
or surgery
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Other GI Conditions
Irritable Bowel Syndrome (IBS)
• Chronic disease with frequent and painful constipation or
diarrhea; drug therapy is limited, restricted distribution
Ulcerative Colitis and Crohn’s Disease
• Both are excessive inflammation of the GI tract, causing
chronic diarrhea
 Drug therapy includes immunosuppressants,
salicylates, and anti-inflammatory drugs
• Ulcerative colitis can be cured by removing affected
portion of colon or large intestine
• Crohn’s is an autoimmune disease; cannot be cured
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Herbal and Alternative Therapies
• Ginger is used to reduce nausea associated with surgery,
vertigo, and motion sickness
• Probiotics are products that contain live cultures of yeast
or bacteria
 Used for diarrhea, constipation, H. pylori infection,
antibiotic-induced diarrhea
• Lactobacilli are gram-positive bacteria that are normal
flora of the human GI tract
• S. boulardii is a yeast organism in the human GI tract; used
for prevention of diarrhea
• Bifidobacteria agents may be effective for diarrhea
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Summary
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OTC medicines are used to treat diarrhea
Laxatives are used to treat constipation
Topical agents are used to treat hemorrhoids
PPIs and H2 blockers are used to treat GERD and PUD
Antibiotics are also used for PUD caused by H. pylori
Antacids are used for GERD to relieve heartburn from food
Anticholinergic antiemetics treat mild nausea/vomiting
General antiemetics treat nausea in inpatient settings
5-HT3 antagonists (antiemetics) are used for
chemotherapy
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