Gastrointestinal Agents

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Lecture 12

• Gastrointestinal Agents
• Chapters 41 42

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GI Agents

• GI tract Oral cavity of mouth, esophagus,
  stomach, sm. intestine (duodenum, jejunum,
  ilium), lg. intestine (cecum, colon, rectum),
  anus
• Accessory organs contributing to the digestive
  process Salivary glands, pancreas, gallbladder,
  liver
• Main function Digestion of food particles
  absorption of digestive contents (nutrients,
  electrolytes, minerals, fluids) - into
  circulatory system for cellular use
• Undigested material passes through the lower
  intestinal tract w/ aid of peristalsis to rectum
  anus - excreted as feces or stool

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GI AgentsVomiting - Antiemetics

• Vomiting the expulsion of gastric contents
  Before treating, the cause of the vomiting needs
  to be identified
• Causes are many motion sickness, viral
  bacterial infection, food intolerance, surgery,
  PG, pain, shock, effects of some drugs,
  radiation, disturbances of the middle ear
  affection equilibrium.
• Antiemetics can mask the cause should not be
  used until cause is determined, unless vomiting
  is severe enough to cause dehydration
  electrolyte imbalance

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GI AgentsVomiting - Antiemetics

• Two major cerebral centers are the chemoreceptor
  trigger zone (CTZ), which lies near the medulla,
  the vomiting center, in the medulla - both
  cause vomiting when stimulated
• The CTZ receives most of the impulses from drugs,
  toxins, and the vestibular center. The
  neurotransmitter dopamine stimulates the CTZ,
  which stimulates the vomiting center, when
  triggered, motor neuron responds ? contraction of
  diaphragm, anterior abdominal muscles, the
  stomach. the glottis closes, the abdominal wall
  moves, upward vomiting occurs.

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GI AgentsAntiemetics

• Nonpharm Rx weak tea, flattened carbonated
  drinks, Gatorade pedialyte (children), crackers
  dried toast
• Nonprescription antiemetics used to prevent
  motion sickness - minimal effect on severe
  vomiting from anticancer agents, radiation, and
  toxins.
• - take 30 min. before traveling
• Dimenhydrinate (dramamine), meclizine HCL
  (Antivert), diphenhydramine HCL (Benadryl)
• - SE drowsiness, dryness of mouth,
  constipation

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GI Agents-Antiemetics

• bismuth subsalicylate (Pepto-Bismol) - act
  directly on gastric mucosa to suppress vomiting -
  liquid chewable taken for gastric discomfort
  diarrhea

• Phosphorated carbohydrate (Emetrol)
  Hyperosmolar carbohydrate ?decreases NV by
  changing the gastric pH

• Antiemetics were used in the 1st trimester of
  PG , but no more ? due to poss. harm to fetus.
  Non pharm methods should be used OTC
  antiemetics avoided ? unless N V become life
  threatening to mom baby. Then use Tigan given.

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GI AgentsAntiemetics

• Prescription Antiemetics - eight categories
• 1 2. Antihistamines Anticholinergics -
  Hydroxyzine (Vistaril, Atarax), Promethazine
  (Phenergan), Scopolamine (Transderm Scop) - Act
  primarily on the vomiting center, dec.
  stimulation of CTZ
• - SE drowsiness, dry mouth, blurred vision
  (pupil dilation), tachycardia (anticholinergics),
  constipation
• - Do not use in clients w/ glaucoma d/t
  dilation of pupils

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GI Agents - Antiemetics
3. Dopamine antagonists - blocks dopamine-2
receptors in the CTZ. SE Extrapyramidal
symptoms (tremors, mask face, rigidity, shuffling
gait)

• Phenothiazine - largest group of drugs used for N
  V
• Chlorpromazine (Thorazine), prochlorperazine
  edisylate (Compazine) - most frequently
  prescribed, perphenazine (Trilafon) - frequently
  used w/ anticancer therapy
• - Action - inhibits dopamine in the CTZ thus
  dec. CTZ stimulation of the vomiting center
• - Use - severe N V from sugery,
  anesthetics, chemo radiation sickness
• - SE dry mouth, drowsiness, EPS, dizziness,
  hypotension

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GI Agents - Antiemetics
Perphenazine (Trilafon) used with anti cancer
therapy, inhibits dopamine in the CTZ ?
decreasing CTZ stimulation vomiting center, also
an antipsychotic
Onset 2 6 h, duration 6-12 h Interactions
Taken with ETOH, antihypertensive agents, and
nitrates, hypotension can result
CNS depression when taken with ETOH, narcotics,
sedative- hypnotics and general anesthetics
SE moderate sedation hypotension, EPS (
parkinsonism) CNS effects (restlessness,
weakness, dystonic reactions, agitation), and
mild anticholinergic s/s (dose lower as
antiemetic than antipsychotic, so SE not as
severe.
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GI AgentsAntiemetics

• Butyrophenones - Haloperidol (Haldol),
  droperidol (Inapsine) - block dopamine-2
  receptors in the CTZ
• - Use - Rx of post-op N V emesis
  associated w/ toxins, chemo radiation therapy
• - SE - EPS if used over extended time,
  hypotension
• Metoclopramide - metoclopramide (Reglan) -
  blocks dopamine serotonin receptors in the CTZ
• - Use post-op emesis, chemo radiation
  therapy
• - SE sedation diarrhea w/ high doses

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GI AgentsAntiemetics

• 4. Benzodiazepines - Lorazepam (Ativan) - for N
  V d/t chemo - May be given w/ an antiemetic such
  as metoclopramide (Reglan)
• 5. Serotonin Antagonists - ondansetron (Zofran),
  granisetron (Kytril) -
• - Action - suppress N V by blocking the
  serotonin receptors in the CTZ afferent vagal
  nerve terminals in upper GI tract - Do not cause
  EPS symptoms
• - Use - chemo induce emesis - PO IV
• - SE - headache, diarrhea, dizziness, fatigue

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GI Agents - Antiemetics

• 6. Glucocorticoids - Dexamethasone (Decadron),
  methylprednisolone (Solu-Medrol) - effective w/
  chemo treatment in suppressing emesis - given IV
• 7. Cannabinoids - active ingredient in marijuana
  - approved for clinical use since 1985 to
  alleviate N V from cancer treatments -
  dronabinol (Marinol), nabilone (Cesamet)
• - for clients unable to use or respond to
  other antiemetics
• - SE mood changes, euphoria, drowsiness,
  nightmares, dry mouth, confusion, HA,
  depersonalization, nightmares, incoordination,
  memory lapse, orthostasis, hypertension
  tachycardia

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GI AgentsAntiemetics/Emetics

• 8. Miscellaneous - Benzquinamide HCL (Emete-Con),
  diphenidol (Vontrol), trimethobenzamide (Tigan) -
  suppress the impulses to the CTZ, Vontrol also
  prevents vertigo by inhibiting impulses to the
  vestibular area
• - labeled misc. because they dont act
  strictly as antihistamines, anticholinergics, or
  phenothiazides
• - SE drowsiness, anticholinergic symptoms,
  CNS stimulation, EPS

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GI Agents - Emetics

• Emetics - for when an individual has consumed
  certain toxic substances and must be expelled
  before absorption -- Dont induce vomiting if
  caustic substances have been ingested, ? ammonia,
  chlorine bleach, lye, toilet cleaners, or battery
  acid. Activated charcoal is given when emesis is
  CI
• Ipecac - stimulates the CTZ in the medulla
  acts directly on the gastric mucosa - take w/
  water (not milk or carbonation) - onset in 15 to
  30 min. Repeat tx if needed. Toxic if absorbed
  ? give charcoal.
  
  - s/s toxicity ? hypotension,
  tachycardia, chest pain
  SE diarrhea, sedation, lethargy
• Apomorphine is a morphine derive emetic, SQ/IM,
  Onset 15 min

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GI Agents - Antidiarrheals

• Diarrhea frequent liquid stool d/t an
  intestinal disorder
• - causes foods, fecal impaction, bacteria,
  virus, drug rxn, laxative abuse, malabsorption
  syndrome, stress, bowel tumor, inflammatory bowel
  disease
• - can be mild to severe - ID underlying causes
  first
• - can cause minor or severe dehydration
  electrolyte imbalance
• - can be life threatening to the young
  elderly
• Nonpharm Rx clear liquids oral solns
  (gatorade, pedialyte), IV electrolyte solns..
  (BRAT diet)

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GI Agents - Antidiarrheals

• Used to decrease hypermotility (inc. peristalsis
  cause of diarrhea - needs to be corrected) Do
  not use longer that 2 days not use with fever.
  Underlying cause must be found. (Ex. E. Coli)
• 4 categories (Opiates, opiate related agents,
  adsorbents antidiarrheal combos)
• Opiates - decrease intestinal motility thus dec.
  peristalsis
• tincture of opium, paregoric, codeine - in
  combo w/ other agents
• SE CNS depression ( taken with ETOH,
  sedatives or tranqs), constipation
  Duration 2 hrs.
• Opiate-Related Agents - Diphenoxylate (Lomotil),
  loperamide (Imodium) - synthetic drugs chemically
  related to meperidine
• - Action - decrease intestinal motility -
  travelers diarrhea
• - SE N V, drowsiness, abd. Distention

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GI Agents - Antidiarrheals

• Imodium works against diarrhea longer than
  similar dose of Lomotil
  
  Lomotil is approx 50 atropine (to
  discourage abuse), Action time of 45 60
  mins. Duration 3-4 hrs.
• - CI in hepatic diesease, glaucoma - SE many
  due to atropine ? dry mouth, urinary retention,
  dec secretions.

• Adsorbents - coat the wall of the GI tract and
  adsorbing the bacteria or toxins causing diarrhea
  (Substance takes in toxin)
• - Kaopectate (kaolin pectin) OTC
• - Pepto-Bismol adsorbs bacterial toxin for GI
  discomfort, OTC

Miscellaneous Furazolidone Lactobacillus
acidophilus
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GI AgentsConstipation

• Constipation - accumulation of hard fecal
  material in the large intestine - a major problem
  of the elderly
• - Causes - poor H2O intake poor dietary
  habits, ignoring the urge, fecal impaction,
  bowel obstruction, chronic laxative use,
  neurologic disorders (paraplegia), lack of
  exercise, selected drugs (anticholinergics,
  narcotics certain antacids)
• Nonpharm Rx diet that contains fiber, water,
  exercise, routine bowel habits (normal can be
  1-3/day or 3/wk varies from person to person)
  The freq. is secondary to consistency feces
  hard dry

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GI Agents - Constipation

• Pharmacologic measures ? laxatives cathartics
• - Laxatives inc. peristalsis , promote soft
  stool
• - cathartics - result in soft to watery stool
  with some cramping
• Use painful elimination due to episiotomy,
  hemorrhoiods anorectal leisions cardiovascular
  disease, prior to surg. or tests

• Laxative abuse from chronic use a problem, esp.
  with elderly client teaching
• Laxatives should be avoided if there is any
  question of pts. having an intestinal
  obstruction, severe abd. pain, symptoms of
  appendicitis, ulcerative colitis, or
  diverticulitis

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GI Agents -Laxatives

• Osmotic Laxatives (Hyperosmolar laxatives) -
  include salts or saline products, lactulose,
  glycerine
• Lactulose (Cephulac), Magnesium hydroxide
  (MOM), sodium biphosphate (Fleet Phospho-Soda),
  Fleet enema
• Action These poorly absorbed salts osmotic
  action draws water into the intestine, inc. H20
  causes fecal mass to soften and swell ? stretches
  intestine stimulate peristalses.
• Saline preps contains NA, Mg, a small amt.
  may be systemically absorbed so CI in poor renal
  function

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GI Agents - Laxatives

• Osmotic laxatives contain 3 electrolytes (NA,
  MG, K) Used in bowel prep for dx surg.
  procedures
• Polyethylene glycol (PEG) or (GoLytely) non
  absorbable osmotic substance, so can be used by
  clients with renal impair or cardiac probs, PO
  3 to 4 liters over 3 hours for bowel prep.
• Lactulose (saline lax) draws H2O into the
  intestines
• - SE flatulence, diarrhea, abd. cramping, N
  V
• CI Clients w/ CHF, w/ renal insufficiency
  should avoid magnesium salts, in some laxatives
  (Milk of Mag)
• Electrolytes should be monitored.

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GI AgentsLaxatives

• Stimulant (Contact) Laxatives - Increase
  peristalsis by irritating sensory nerve endings
  in the intestinal mucosa
• phenolphytalein (Ex-Lax), biscadyl (Dulcolax),
  senna (Senokot), castor oil (purgative)
• - Biscadyl phenolpythalein are two of the
  most frequently used abused laxatives - OTC
• - Castor Oil harsh laxative that acts on the
  small bowel produces a watery stool
• - SE Nausea, abd. cramps, weakness, Fluid
  electrolyte imbalances w/ chronic use

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GI Agents - Laxatives

• Bulk-Forming Laxatives - Calcium polycarbophil
  (FiberCon), methylcellulose (Citrucel), psyllium
  hydrophilic mucilloid (Metamucil)
• - Natural fibrous substances that promote lg.
  soft stools by absorbing water into the intestine
  - inc. fecal bulk peristalsis
• - Does not cause laxative dependence may be
  used by clients w/ diverticulosis, irritable
  bowel syndrome ileostomy colostomy
• - Powders mixed w/ H2O or juice, drink
  immediately, followed by a full glass

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GI Agents - Laxatives

• Emollients (Surfactants) - Docusate calcium
  (Surfak), docusate potassium (Dialose), docusate
  sodium (Colace), docusate sodium w/ casanthranol
  (Peri-Colace) - Stool softeners (surface acting
  drugs) and lubricants used to prevent
  constipation - dec. straining during defecation
• - Action - lowers surface tension promotes
  H2O accumulation in the intestine and stool
• - Use - after an MI, post-op
• - SE - N V, diarrhea, cramping

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GI AgentsAntiulcer Drugs

• Peptic Ulcer - a broad term for an ulcer
  occurring in the esophagus, stomach, or duodenum
  w/in the upper GI tract (esophageal, gastric
  duodenal ulcers).
• Ulcers develop when there is an imbalance
  between mucosal defensive factors aggressive
  factors. Maj. defensive factors are mucus
  bicarb. (Keep stomach duodenun from
  selfdigestion) Major aggressive - H. pylori,
  NSAID, gastric acid, pepsin
• Duodenal ulcers 10X more frequent than gastric,
  esophageal
• Release of hydrochloric acid (HCL) from the
  parietal cells of the stomach influenced by
  histamine, gastrin acetylcholine - Peptic
  ulcers caused by hypersecretion of HCL pepsin,
  erode the GI mucosal lining

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GI AgentsAntiulcer Drugs

• Gastric secretions of the stomach strive to keep
• a pH of 2 to 5 Pepsin-a digestive enzyme
  is activated at a pH of 2, the acid-pepsin
  complex of gastric secretions can cause mucosal
  damage
• - If the pH inc. to 5 - the activity of
  pepsin declines
• Gastric Mucusal Barrier (GMB) - thick, viscous,
  mucous material that provides a barrier between
  the mucosal lining the acidic gastric
  secretions - defense against corrosive
  substances, maintains integrity of the gastric
  mucosal lining

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GI Agents - Antiulcer Drugs

• Two sphincter muscles
• - Cardiac - located at the upper portion of
  the stomach - prevents reflux of acid into the
  esophagus
• - pyloric - located at the lower portion of
  the stomach - prevents reflux of acid into the
  duodenum
• Esophageal ulcers ? reflux of acidic gastric
  secretion into the esophagus d/t a defective or
  incompetent cardiac sphincter
• Duodenal ulcers ? hypersecretion of acid from
  the stomach that passes to the duodenum
• Gastric ulcer ? breakdown of GMB (gastric
  mucosal barrier)

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GI Agents - Antiulcer Drugs

• Predisposing factors - mechanical disturbances,
  genetic, bacterial organisms, environmental,
  drugs - Nurse needs to help identify teach ways
  to avoid
• Symptoms gnawing, aching pain
• - gastric 30 min. 1 1/2 h after eating
• - duodenal - 2 - 3 h after eating
• Stress ulcer usually follows a critical situation
  - trauma, major surgery - prophylactic use of
  antiulcer drugs dec. the incidence of stress
  ulcers

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GI Agents - Antiulcer Drugs

• Helicobacter pylori (H. pylori) - a gram (-)
  bacillus linked w/ the development of peptic
  ulcer
• - H. pylori known to cause gastritis, gastric
  ulcer duodenal ulcer When a peptic ulcer
  recurs after anti-ulcer tx and its not caused by
  NSAIDS such as ASA or Ibuprofen client should be
  tested for H. pylori

- A noninvasive breath test is used or serology
to check for antibodies of H. pylori
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GI Agents Antiulcer
Before the breath test an endoscopy bx. Needed
both to detect H. pylori. Meretek UBT is a
breath test. Pt. Drinks a liquid containing 13 C
urea then breaths into a container. If H
pylori is present the bacteria releases 13CO2.
90 95 effective - Various protocols for
treatment - dual, triple, or quadruple drug
therapy program using various antibacterial
agents antiulcer drugs - the combo of drugs
differs for each client, depends on the
sensitivity of the bacteria, H pylori is readily
resistant to drugs. Rx for 7 to 14 days
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GI Agents - Antiulcer Drugs

• Gastroesophageal reflux Disease (GERD) - 40 to
  45 of adults have heartburn in many cases d/t
  GERD
• - Inflammation of the esophageal mucosa caused
  by reflux of gastric acid content into the lower
  esophageal sphincter
• - Rx similar to treatment of peptic ulcers - the
  use of common antiulcer drugs to neutralize
  gastric contents reduce acid secretion
• - A chronic disorder requiring continuous
  management education

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GI AgentsAntiulcer Drugs

• Nonpharm Rx avoiding smoking ETOH can dec.
  gastric secretions, wt. loss (obesity enhances
  GERD), avoid hot, spicy, greasy foods, Take
  NSAIDs w/food, do not eat before bedtime
• Pharmacologic Rx there are 8 groups of
  antiulcer agents
• 1. Tranquilizers - minimal effect in preventing
  treating ulcers. Reduce vagal stimulation dec.
  anxiety
• Librax - combo of anxiolytic chlordiazepoxide
  (Librium) the anticholinergic clidinium
  (Quarzan) used in the treatment of ulcers

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GI AgentsAntiulcer Drugs

• 2. Anticholinergics - Not used as much w/ the
  newer drugs on board. Relieve pain by dec. GI
  motility secretion
• 3. Antacids - Promote ulcer healing by
  neutralizing HCL reducing pepsin activity they
  do not coat the ulcer, Two types Systemic or
  non systemic
• Calcium carbonate (Tums)- Systemically
  absorbed antacid - neutralizes acid, however, 1/3
  to 1/2 of drug systemically absorbed causes
  acid rebound. Hypercalcemia can result from
  excess use
• Sodium bicarb.- systemically absorbed many SE
  hypernatremia, water retention are a few

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GI AgentsAntiulcer Drugs

• Nonsystemic antacids composed of alkaline salts -
  aluminum (aluminum hydroxide - Amphojel) and
  magnesium (magnesium hydroxide - Maalox, Mylanta)
• - The combo of magnesium aluminum
  neutralizes gastric acid w/o causing constipation
  or severe diarrhea
• - aluminum itself causes constipation
  magnesium alone can cause diarrhea
• - Ideal dosing is 1 and 3 h after meals

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GI AgentsAntiulcer Drugs

• 4. Histamine -2 Blockers (H2) or histamine-2
  receptor antagonists - most popular drugs used to
  treat ulcers
• - Action - Block the H2 receptors of the
  parietal cells in the stomach, thus reducing
  gastric acid secretion concentration to promote
  healing
• Cimetidine (Tagamet), Famotidine (Pepcid),
  Nizatidine (Axid), ranitidine (Zantac)
• - Tagamet first H2 blocker - Need good kidney
  function, 50-80 of drug excreted unchanged in
  the urine
• do not give w/ antacids - dec. effectiveness
  of drug

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GI Agents - Antiulcer Drugs

• - Zantac, Pepid, Axid more potent in
  addition to blocking of gastric secretion they
  also promote healing of the ulcer by eliminating
  its cause.
• - Duration of action longer fewer side
  effects
• - Use - to treat gastric duodenal ulcers
  can be used prophylactically
• also useful in relieving symptoms of reflux
  esophagitis, preventing stress ulcers post-op
• - SE headaches, dizziness, constipation, rash
• - DI many w/ cimetidine - check carefully

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GI AgentsAntiulcer Drugs

• 5. Proton Pump Inhibitors (gastric acid secretion
  inhibitors, gastric acid pump inhibitors (PPIs) -
  suppress gastric acid secretion by inhibiting the
  hydrogen / potassium ATP-ase enzyme system
  located in the gastric parietal cells, they tend
  to inhibit gastric acid secretion up to 90
  greater than the H2 blockers - these agents block
  the final step of acid production
• Omeprazole (Prilosec), lansoprazole (Prevacid)
  - Used for Rx of peptic ulcers GERD - highly
  protein-bound
• SE headache, dizziness, diarrhea, abd. pain,
  rash
• Monitor liver enzymes

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GI AgentsAntiulcer Drugs

• 6. Pepsin Inhibitor - Sucralfate (Carafate) - a
  mucosal protective drug. Nonabsorbable combines
  w/ protein to form a viscous substance that
  covers the ulcer and protects it from acid
  pepsin - does not neutralize acid or dec. acid
  secretions
• - SE - few because not systemically absorbed,
  but may cause nausea constipation
• 7. Prostaglandin analogue antiulcer drug -
  Misoprostol (Cytotec) - New for prevention Rx
  of peptic ulcers

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GI Agents - Antiulcer Drugs

• - Action - It appears to suppress gastric acid
  secretion inc. cytoprotective mucus in the GI
  tract. Causes a mod. dec. in pepsin secretion
• - Use - gastric distress from taking NSAIDs,
  ASA indomethacin that are prescribed for
  long-term therapy
• - CI - during pregnancy for women of child
  bearing yrs.
• 8. GI stimulants - Cisapride (Propulsid) -
  increases gastric emptying time preventing acid
  reflux - used for nocturnal heartburn GERD
• CI - cardiac dysrhythmias, heat disease, CHF
  - an ECG should be done before during therapy,
  renal resp. failure

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Action of Anti-Ulcer drug groups