Transcript Nursing 3703 Pharmacology Digestive System Drugs

Nursing 3703
Pharmacology
Digestive System Drugs
By Linda Self APN, MSN, CCRN
Effects of Drugs on the Digestive
System
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Digestive system and drug therapy have a reciprocal
relationship
Some medications cause GI symptoms (e.g. EES);
conversely, some GI disorders alter the absorption
and metabolism of drugs (liver failure)
Drugs affecting the GI tract include: laxatives,
antidiarrheals, antiemetics, drugs used in acid-peptic
disorders . Others include cholinergics (Aricept)
anticholinergics (atropine), corticosteroids and antiinfectives.
Review physiology of the digestive system
Organs and some associated disorders
 Oral cavity-stomatitis
 Esophagus-GERD
 Stomach—peptic ulcers, gastritis
 Small intestine—malabsorption, Inflammatory bowel
 Large intestine—diarrhea, constipation
 Pancreas—pancreatitis, Diabetes, ARDS
 Gallbladder—cholestasis,cholelithiasis, cholecystitis
 Liver—hepatitis, cirrhosis
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Cell protective mechanisms in
stomach
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Secretion of mucus and bicarbonate
Dilution of gastric acid by food and secretions
Prevention of diffusion of HCL from the
stomach lumen back into the gastric mucosal
lining
Presence of prostaglandin E
Alkalinization of gastric secretions by
pancreatic juices and bile
Cell Destructive Effects in Stomach
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Gastric acid, secreted by parietal cells
Paretal cells contain receptrors for
acetylcholine, gastrin and histamine, all of
which stimulate gastric acid production
Acetylcholine is released by vagus nerve
endings in response to stimuli, such as thinking
about food
Cell destructive effects cont.
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Gastrin is a hormone released by the stomach
and duodenum in response to food ingestion.
Affects parietal cells which in turn causes
gastric acid to be released in stomach.
Histamine is released from cells in the gastric
mucosa and diffuses into nearby parietal cells
Pepsin is a proteolytic enzyme that helps
digest protein foods and also can digest the
stomach wall
Cell destructive effects
H. pylori is a gram negative bacterium found in
the gastric mucosa of most clients with chronic
gastritis
 In 75% of those with gastric ulcers and in 90%
of clients with duodenal ulcers
 Spread by oral fecal route or by iatrogenic
spread
 Thought to affect mucosal function
Peptic Ulcer Disease
Gastric Ulcers
 Associated with stress, NSAIDs or H. pylori
 Manifested by painless bleeding
 Take longer to heal than duodenal ulcers
 When associated w/stress, can occur at any age
 With H. pylori and NSAIDs generally are in
6th or 7th decade
 chronic
PUD cont.
Duodenal Ulcers
 Can occur at any age
 Occur equally in men and women
 Manifested by abdominal pain
 Associated with cigarette smoking
 Also associated with NSAIDs and H. pylori
Peptic Ulcer and Acid Reflux
Disorders
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Characterized by ulcer formation in the
esophagus, stomach or duodenum
Occurs in areas that are exposed to gastric acid
and pepsin
Gastric and duodenal ulcers are more common
than esophageal ulcers
Parietal cells contain receptors for
acetylcholine—implication of which is
stimulation by/of vagus
Upper GI Disorders
Gastritis—acute or chronic inflammatory reaction of
gastric mucosa.
Usually will see peptic ulcers with gastritis
 Non-steroidal anti-inflammatory Drug Gastropathy
 Occurs with damage to mucosa by ASA or other
NSAIDs
Chronic ingestion causes irritation of the gastric
mucosa, inhibits the synthesis of prostaglandins
(which protect mucosal lining) and increasess the
synthesis of leukotrienes and other substances that
can cause mucosal damage
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Selected Upper Gastrointestinal
Disorders
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Review p. 853 in text
Include Gastritis
Nonsteroidal anti-Inflammatory Drug Gastropathy
Stress Ulcers
Zollinger-Ellison Syndrome-rare; excessive secretion
of gastric acid and a high incidence of ulcers. Caused
by gastrin-secreting tumors in pancreas, stomach or
duodenum. Often malignant.
Gastroesophageal Reflux Disease
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Most common disorder of the esophagus
Characterized by regurgitation of gastric contents into
the esophagus
Occurs most often after a meal
Worse when recumbent
Caused by incompetent lower esophageal sphincter
Foods that cause relaxation include: etoh, caffeine,
fats, chocolate, cigarrette smoking, gastric distention
and medications (beta adrenergic blockers, calcium
channel blockers, nitrates)
GERD cont.
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Occurs in men, women, and children
Common during pregnancy
More common after 40 years of age
Classifications and Individual Drugs
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Antacids—alkaline substances that neutralize
acids. Raising the pH to approximately 3.5
neutralizes more than 90% of gastric acid and
inhibits conversion of pepsinogen to pepsin.
Commonly used antacids are aluminum,
magnesium, and calcium compounds.
Antacids
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Antacids vary in onset of active and dosage needed
for neutralization
Aluminum compounds require large doses for
effectiveness. They can cause constipation,
hypophosphatemia and osteomalacia.
Magnesium based antacids have more rapid onset
than Al++ but can cause diarrhea and
hypermagnesemia
Calcium compounds can cause hypercalcemia and
hypersecretion of gastric acid==“rebound”
Antacids
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May be in combinations such as aluminum and
magnesium hydroxide
Decreases the diarrhea and constipation
Most antacids are pregnancy category C
Antacids may be used in children
Antacides with magnesium are contraindicated
because hypermagnesemia may result
Additives such as simethicone may be added
pills are as effective as liquids
Use in Older Adults
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Smaller doses as they secrete less acid
May have some renal compromise
Older adults often take large doses of NSAIDs
H2 receptor antagonists sometimes cause more
side effects
Sucralfate is well tolerated
PPIs are drugs of choice in this population
Helicobacter pylori
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Requires combination of two antimicrobials and a
PPI or an H2RA
Use amoxicillin, clarithromycin, metronidazole or
tetracycline for antibiotic portion
More than antimicrobial is indicated to prevent
resistance
Bismuth compound is added for its antibacterial
effects as well as increasing the HCO3- and mucous
contents of the stomach
Adding an H2RA or PPI decreases S/S and hastens
healing
Histamine 2 Receptor Antagonists
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Histamine release causes contraction of
smooth muscle in bronchi, GI tract, increases
permeability of capillaries,stimulation of
sensory nerve endings and strong stimulation
of gastric acid secretion
Vagal stimulation causes release of histamine
from cells in stomach, acts on receptors in
parietal cells>>>>increases HCL production.
Called H2 receptors
Histamine 2 Receptor Antagonists
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Traditional antihistamines or H1 receptor
antagonists generally reduce the effects of
histamine in the body but do not block
histamine effects on gastric acid production.
Replaced as first choice drugs by the PPIs
Prototype is cimetidine
Generally are pregnancy category B
May have multiple drug interactions and SE
Available OTC and by Rx
H2RA
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Reduce dosage in pregnancy
Cimetidine affects the cytochrome p450 drug
metabolizing system in the liver; may cause
confusion and antiadrogenic effects (gynecomastia)
Ranitidine more powerful
Use for up to 8 weeks
May be used long term but with variable dosing
Antacids may be given concurrently to relieve pain
Proton Pump inhibitors
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Strong inhibitors of gastric acid secretion
Bind irreversibly to the gastric proton pump to
prevent the release of gastric acid from parietal cells
Suppresses acid secretion in response to all primary
stimuli including histamine, gastric, and acetylcholine
Are the drugs of first choice in erosive esophagitis,
erosive gastritis and Zollinger-Ellison
PPIs
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More effective than H2RA
Faster symptom relief and faster healing
Used in prevention of esophagitis
Tx H. pylori associated ulcers
Side effects are nausea, diarrhea and HA
Long term effects??? Implications??
Prostaglandin
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Naturally occurring prostaglandin E is
produced by mucosal cells of the stomach and
duodenum. It inhibits gastric acid secretion
and increases mucous and bicarbonate,
mucosal blood flow and mucosal repair. With
inhibition of Prostaglandin E, erosion and
ulceration of the gastric mucosa may occur.
Implications
Cytotec (misoprostol)
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Synthetic form of prostaglandin E
Indicated for clients at high risk for GI
ulceration and bleeding and in those who take
NSAIDs
Contraindicated in women of childbearing
age and during pregnancy (see text p. 862)
May induce abortion
Side effects include diarrhea and abdominal
cramping
Sucralfate
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Preparation of sulfated sucrose and aluminum
hydroxide that binds to normal and ulcerated mucosa
Mechanism of action is unclear
Thought to possible bind to the ulcer and form a
protective barrier between the mucosa and gastric
acid, pepsin and bile salts; and stimulating
prostaglandin synthesis
Effective in healing duodenal ulcers and in prevention
of recurrence
Sucralfate
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Side effects include constipation and dry
mouth
Must be given Bid
Cannot be given with an antacid, H2RA or PPI
May bind other drugs and prevent their
absorption
Give 2 hours before or after other drugs
Effects of Acid Suppressant Drugs
on Nutrients
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Dietary folate, iron and Vitamin B12 are better
absorbed from an acidic environment
Less acidic environment can cause deficiencies
of these nutrients
Sucralfate interferes with the absorption of the
fat soluble vitamins
Magnesium containing antacids interfere with
absorption of Vitamin A
Nursing Actions
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Review administration on p. 865-867
Antiemetics
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Used to prevent or treat nausea and vomiting
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Vomiting is the expulsion of stomach contents
through the mouth
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Vomiting can occur w/o nausea
Origin of vomiting
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Vomiting center is located in medulla
oblongata
Stimuli are relayed to the vomiting center from
the periphery (gastric mucosa, peritoneum,
intestines, joints(?)) and centrally (from the
cerebral cortex; vestibular apparatus and from
neurons in the fourth
ventricle==chemoreceptor trigger zone) sites
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The vomiting center, chemoreceptor trigger zone and
GI tract contain benzodiazepine, cholinergic,
dopamine, histamine, opiate and serotonin receptors
that are stimulated by emetogenic drugs and toxins
For example: chemotherapy may stimulate the CTZ
which then signals the vomiting center
Motion sickness—changes in body
motion>>stimulate receptors in inner
ear>>transmitted to the CTZ and the vomiting center
Triggering the vomiting center
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Efferent impulses cause glottic closure
Contraction of abdominal muscles and
diaphragm
Relaxation of the GE sphincter
Reverse peristalsis
Projection or expulsion
Causes of nausea and vomiting
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Pain
Emotional disturbances
Radiation therapy
Motion sickness
Drug therapy: especially with alcohol, ASA,
digoxin, anticancer drugs, antimicrobials,
estrogen preparations and Opioids
Causes of Nausea and Vomiting
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GI disorders such as inflammation of the GI
tract, liver, gallbladder, pancreas, impaired GI
motility and muscle tone (gastroparesis) and
ingestion of food that is irritating to the
mucosa
Cardiovascular, infectious, neurologic or
metabolic disorders
Antiemetic Drugs
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Most have anticholinergic, antidopaminergic,
antihistaminic or antiserotonergic effects
Generally are more effective in prophylaxis
than treatment
Most act on the vomiting center, the
chemoreceptor trigger zone, the cerebral
cortex, vestibular apparatus or any of the
above
Antiemetic Drugs
Phenothiazines—CNS depressants used in psychoses
 Block dopamine from receptor sites in the brain
 Act on CTZ and the vomiting center
 Not all phenothiazines are anti-emetics
 Cause drowsiness
 Prochlorperazine (Compazine) and promethazine
(Phenergan) are examples
 Some are pregnancy category B, others C, should
check 1st
Side effects continued
Extrapyramidal symptoms which include:
Dyskinesias (rhythmic movements), dystonias
(rhythmic jerks) and akathesia (inability to sit
still) related to dopamine receptor blockade
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Antihistamines
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Prevent histamine from exerting its widespread
effects on the body
Classic antihistamines or H1 receptor blocking
agents are thought to block the action of
acetylcholine in the brain (anticholinergic)
Indicated in Motion sickness
Examples are Dramamine, hydroxyzine
(Vistaril), meclizine (Antivert)
Corticosteroids
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May affect prostaglandin activity in the
cerebral cortex
Dexamethasone and methyprednisolone are
commonly used in the management of
chemotherapy induced emesis, usually in
combination with other anti-emetics
Benzodiazepine antianxiety drugs
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Not classic anti-emetics but often used in
multidrug regimens to prevent nausea and
vomiting associated with cancer chemotherapy
Inhibit cerebral cortex input to the vomiting
center
May give to those with anticipatory nausea
before chemotherapy
Example is Ativan (lorazepam)
5 Hydroxytryptamine (5-HT3 or
Serotonin)Receptor Antagonists
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Ondansetron, granisetron and dolasetron are
used to prevent or treat moderate to severe
nausea and vomiting r/t cancer chemotherapy,
radiation therapy and postoperatively
Some anticancer drugs seem to affect a subset
of 5-HT3 recptors in the CTZ and the GI tract
These drugs antagonize receptors both
peripherally (GI) and in the CTZ to prevent
activation
5-HT3 receptor antagonists cont.
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Can be given IV or orally
Side effects are mild to moderate and include:
diarrhea, headache, dizziness, constipation,
muscle aches and transient liver enzymes
elevation
Ondansetron (Zofran) is the prototype
Metabolized by the liver
Miscellaneous Antiemetics
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Dronabinol (Marinol) is a cannabinoid used in
the management of nausea and vomiting
associated with anticancer drugs and
unrelieved by other drugs.
Schedule III under federal narcotic laws
Withdrawal S/S may occur
Sleep disturbances
Reglan
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Prokinetic that increases GI motility and the
rate of gastric emptying by increasing the
release of acetylcholine from nerve edings in
the GI tract
Can cause decreased n/v associated with
gastroparesis
Has central antiemetic effects, antagonizes the
action of dopamine
Can be given IV, PO or IM
Reglan continued
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Side effects include sedation, restlessness, and
extrapyramidal reactions
May increase the effects of alcohol and
cyclosporine and decrease the effects of
cimetidine and digoxin (decrease time for
passage)
Emetrol
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Phosphorated carbohydrate solution
Hyperosmolar solution with phosphoric acid
OTC
Felt to work by reducing smooth muscle
contraction in the GI tract
Scopolamine
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Anticholinergic drug
Transdermal patch
Excellent for motion sickness
Contraindications
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When can delay or prevent diagnosis
When s/s of toxicity may be masked
Reglan is relatively contraindicated in
Parkinson’s disease because it further dples
dopamine
Management Considerations
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5-HT3 antagonists 1st choice in chemotherapy
induced or postoperative N/V
Drugs with anticholinergic and antihistaminic
properties are preferred for motion sickness
If ambulatory, opt for drug that causes less
sedation
Phenergan is used for its antihistaminic,
antiemetic and sedative effects
Management Considerations cont.
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Phenothiazines can have serious side effects
Reglan may be preferred for non-obstructive
gastric retention
Herbals
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Efficacy still debatable
Chemotherapy-induced Nausea and
Vomiting
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Chemo may be given during sleeping hours
Decrease food intake few hours before Tx
Antiemetics should be given before the emetogenic
Tx and may be given for 2-3 days
5-HT2 receptor antagonists are drugs of choice for
this indication
Reglan is valid option but may need to give
diphenhydramine to prevent the EPS
Sometimes combo of steroid and 5-HT3 RA useful
Laxatives and Cathartics
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When stomach and duodenum are distended with
food, gastrocolic and duodenocolic reflexes are
initiated
The cerebral cortex controls the defecation reflex so
that defecation can occur at acceptable times and
places
In people who inhibit the defecation reflex or fail to
respond to the urge to defecate, constipation develops
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Laxatives are chemical substances that act to
facilitate passage of bowel contents
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Cathartics—a purgative action of the bowels,
action is stronger and generally produces
elimination of liquid stools
Indications for Use
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Reduce cholesterol
Obtain stool sample
Accelerate excretion of parasites after anthelminthics
started
Accelerate elimination of potentially toxic substances
(Kayexalate)
Pre-op
Prevent straining at stool w/CAD, hemorrhoids
Relieve constipation in pregnancy, in the elderly; in
children with megacolon, and in those w/decreased
motility
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Laxatives and cathatics should not be used in
the presence of undiagnosed abdominal pain
Could cause an inflamed organ to rupture
Oral agents are contraindicated in intestinal
obstruction and fecal impaction
Laxatives
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Bulk-forming laxatives—Citrucel, Metamucil
Surfactant Laxatives—mainly prevent
straining. They allow water to penetrate stool
and act as detergent to facilitate admixing of
fat and water in the stool. Colace (docusate) or
Surfak.
Saline—magnesium citrate. Nulytely.Increase
osmotic pressure in intestinal lumen.Not safe
for frequent use. Affect fluids and lytes.
Cathartics
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Stimulant type are the strongest and most
abused
Cascara,bisacodyl, castor oil and senna
products
Mineral oil is a lubricant laxative. It slows
colonic absorption of water.
Other
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Lactulose—a disaccharide that is not absorbed from
the GI tract. Pulls water into intestinal lumen. Used to
treat constipation and hepatic encephalopathy.
Lactulose reduces production of ammonia in the
intestine. Can affect lyte and water balance.
Sorbitol—monosaccharide that puls water into the
intestinal lumen and has laxative effects. It is given
with Kayexalate (potassium removing resin to treat
hyperkalemia).
Laxative Abuse
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Public health problem in elderly
Use in patients with cancer
What is normal?
What are some measures to prevent
constipation?
Safety in Use
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Saline cathartics must be used cautiously in the
renally impaired
Lactulose may be indicated in those with
hepatic encephalopathy
Seen frequently in form of enemas in
hyperkalemia in hospital
Antidiarrheals
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Diarrhea is a symptom of numerous conditions
that increase bowel motility; cause secretion or
retention of fluids in the intestinal lumen and
cause inflammation or irritation of the GI
tract. End result: bowel contents are rapidly
propelled and absorption of fluids and
electrolytes is limite.d
Causes of Diarrhea
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Abuse of laxatives
Intestinal infections—E. Coli 0157:H7 (can
result in a hemolytic uremic syndrome),
Traveller’s diarrhea (E. coli), Campylobacter
jejuni, Salmonella, Shigella, rotatvirus
Inflammatory bowel diseases
Drug therapy—pseudomembranous colitis—
Clostridium difficile (anaerobic, spore forming
rods)
Antidiarrheals
Opiate related drugs
 Paregoric
 Defenoxin with atropine—Motofen
 Diphenoxylate with atropine--Lomotil
Antibacterials
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Azithromycin for Traveller’s diarrhea
Cipro—E.coli, Camylobacter, Shigella
EES—amebiasis
Flagyl—Clostridium difficile
Bactrim-Traveller’s diarrhea
Vancomycin—Clostridium difficile, even in
form of enemas
Miscellaneous
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Questran—Crohns’. Binds and inactivates bile
salts in the intestine.
Octreotide—diarrhea associated with HIV,
carcinoid tumors, cancer therapies or
intractable diarrhea caused by other drugs.
Pancreatin—pancreatic enzymes used for
replacement in patients w/deficiency of
pancreatic enzymes