PHARMACOLOGY

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PHARMACOLOGY

• Gastrointestinal drugs

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OBJECTIVES

• Identify classes of drugs used to improve GI
  function.
• Identity uses and varying actions of these drugs.
• Identify how these drugs are absorbed,
  distributed, metabolized, and excreted.
• Identify drug interactions and adverse reactions
  to these drugs.

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DRUGS AND THE GI SYSTEM

• Classes of drugs used to improve GI function
  include
• Peptic ulcer drugs
• Adsorbent, antiflatulent, and digestive drugs
• Antidiarrheal and laxative drugs
• Antiemetic and emetic drugs

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PEPTIC ULCER DRUGS

• Aimed at either eradicating H. pylori or
  restoring balance between acid and pepsin
  secretions and the GI mucosal defense.
• These drugs include systemic antibiotics,
  antacids, Histamine-2 (H2)-receptor antagonists,
  proton pump inhibitors, and other peptic drugs
  such as misoprostol and sucralfate.

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SYSTEMIC ANTIBIOTICS

• Treatment of peptic ulcers caused by H. pylori
  include the use of at least two antimicrobial
  drugs and an antacid for two weeks.
• Systemic antibiotics used to treat H. pylori
  include metronidazole, tetracycline,
  clarithromycin, and amoxicillin.

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SYSTEMIC ANTIBIOTICS

• Pharmacokinetics
• Vary in absorption tetracyclines absorption is
  decreased when taken with dairy products
  distributed widely excreted primarily in the
  urine.
• Pharmacodynamics
• Act by treating the infection.

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SYSTEMIC ANTIBIOTICS

• Pharmacotherapeutics
• Combined with either an H2-receptor antagonist or
  a proton pump inhibitor to decrease stomach acid
  and promote healing.
• Drug interactions
• Tetracycline increases digoxin levels and the
  risk of bleeding when taken with oral
  anticoagulants.

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SYSTEMIC ANTIBIOTICS

• Adverse reactions
• GI disturbances

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ANTACIDS

• Over-the-counter medications that include
• Magnesium hydroxide and aluminum hydroxide
• Simethicone
• Magaldrate
• Calcium carbonate

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ANTACIDS

• Pharmacokinetics
• Work locally in the stomach by neutralizing
  gastric acid.
• Distributed throughout the GI tract eliminated
  primarily in the feces.
• Pharmacodynamics
• Reduces the total amount of acid in the GI tract.

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ANTACIDS

• Pharmacotherapeutics
• Prescribed to relieve pain and promote healing in
  peptic ulcer disease.
• Also used to relieve symptoms of acid
  indigestion, heart-burn, dyspepsia, or GERD.
• Also used to prevent stress ulcers, GI bleeding,
  and hyperphosphatemia in kidney failure.

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ANTACIDS

• Drug interactions
• All antacids can interfere with the absorption of
  oral drugs given at the same time.
• Adverse reactions
• Diarrhea, constipation, electrolyte imbalances

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H2-RECEPTOR ANTAGONISTS

• Commonly prescribed anti-ulcer drugs include
• Cimetidine (Tagamet)
• Nizatidine (Axid)
• Ranitidine (Zantac)
• Famotidine (Pepcid)

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H2-RECEPTOR ANTAGONISTS

• Pharmacokinetics
• Absorbed rapidly and completely except for
  famotidine food and antiacids may reduce
  absorption distributed widely throughout the
  body metabolized by the liver excreted
  primarily in the urine.
• Pharmacodynamics
• Block histamine from stimulating the
  acid-secreting parietal cells of the stomach.

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H2-RECEPTOR ANTAGONISTS

• Pharmacotherapeutics
• Used therapeutically to
• Promote healing of duodenal and gastric ulcers.
• Provide long-term treatment of pathological GI
  hypersecretory conditions.
• Reduce gastric acid production and prevent stress
  ulcers.

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H2-RECEPTOR ANTAGONISTS

• Drug interactions
• Cimetidine inhibits metabolism of ethyl alcohol
  in the stomach resulting in higher blood alcohol
  levels.
• Adverse reactions
• Headache, diarrhea, and rash

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PROTON PUMP INHIBITORS

• Disrupt chemical binding in stomach cells to
  reduce acid production, lessening irritation and
  allowing peptic ulcers to heal.
• These drugs include
• Rabeprazole (Aciphex)
• Pantoprazole (Protonix)
• Omenprazole (Prilosec)
• Lansoprazole (Previcid)

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PROTON PUMP INHIBITORS

• Pharmacokinetics
• Given orally in enteric-coated form to bypass the
  stomach and are dissolved and absorbed in the
  small intestine.
• Highly protein-bound and are extensively
  metabolized by the liver eliminated in the urine.

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PROTON PUMP INHIBITORS

• Pharmacodynamics
• Block the last step in the secretion of gastric
  acid by combining with hydrogen, potassium, and
  adenosine triphosphate in the parietal cells of
  the stomach.

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PROTON PUMP INHIBITORS

• Pharmacotherapeutics
• Indicated for
• Short term treatment of gastric ulcers
• Active duodenal ulcers and peptic ulcers (H.
  pylori)
• Erosive esophagitis
• GERD
• Hypersecretory states

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PROTON PUMP INHIBITORS

• Drug interactions
• May interfere with the metabolism of diazepam,
  phenytoin, and warfarin.
• May also interfere with drugs that depend on
  gastric pH for absorption.
• Adverse reactions
• Abdominal pain, diarrhea, nausea, and vomiting

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OTHER PEPTIC ULCER DRUGS

• Misoprostol (Cytotec) - Protects against peptic
  ulcers caused by NSAIDs by reducing the secretion
  of gastric acid and by boosting the production of
  gastric mucus.
• Sucralfate (Carafate) - Works locally in the
  stomach by rapidly reacting with hydrochloric
  acid to form a thick, paste-like substance that
  adheres to the gastric mucosa.

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ADSORBENT DRUGS

• Prescribed as antidotes for the ingestion of
  toxins which are substances that can lead to
  poisoning or overdose.
• Most commonly used adsorbent drug is activated
  charcoal.
• Pharmacokinetics
• Must be given soon after toxic ingestion not
  absorbed or metabolized excreted unchanged in
  feces.

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ADSORBENT DRUGS

• Pharmacodynamics
• Inhibits toxins from being absorbed in the GI
  tract by attracting and binding with them.
• Pharmacotherapeutics
• A general purpose antidote used for many types of
  acute oral poisoning.

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ADSORBENT DRUGS

• Drug interactions
• Drugs to induce vomiting that had been given
  before administration, now are discouraged so
  administration is not delayed.
• Adverse reactions
• Black stools and constipation.

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ANTIFLATULANT DRUGS

• Disperse gas pockets in the GI tract.
• Simethicone is the major drug currently used.
• Pharmacokinetics
• Not absorbed in the GI tract distributed to the
  intestinal lumen eliminated in the feces.

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ANTIFLATULANT DRUGS

• Pharmacodynamics
• Provide de-foaming action in the GI tract.
• Pharmacotherapeutics
• Used to treat conditions in which excess gas is a
  problem such as functional gastric bloating,
  postop gaseous bloating, diverticular disease,
  spastic or irritable colon, and air swallowing.

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ANTIFLATULANT DRUGS

• Drug interactions
• Dont interact significantly with other drugs.
• Adverse reactions
• None known.

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DIGESTIVE DRUGS

• Aid digestion in patients who are missing enzymes
  or other substances needed to digest food.
• Include
• Dehydrocholic acid
• Pancreatin and pancrelipse.

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DIGESTIVE DRUGS

• Pharmacokinetics
• Arent absorbed act locally in the GI tract
  excreted in the feces.
• Pharmacodynamics
• The action of digestants resembles the action of
  the body substances they replace.
• Dehydrocholic acid - bile
• Pancreatin and pancrelipase - pancreatic enzymes.

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DIGESTIVE DRUGS

• These drugs contain
• Trypsin to digest proteins
• Amylase to digest carbohydrates
• Lipase to digest fats

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DIGESTIVE DRUGS

• Pharmacotherapeutics
• Each digestant has its own indication
• Dehydrocholic acid provides temporary relief of
  constipation.
• Pancreatic enzymes are given to patients with
  pancreatitis, cystic fibrosis, and steatorrhea.

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DIGESTIVE DRUGS

• Drug interactions
• Antacids reduce the effects of pancreatic
  enzymes.
• Adverse reactions
• Diarrhea

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ANTIDIARRHEAL LAXATIVE DRUGS

• Antidiarrheals include opioid-related drugs and
  kaolin and pectin.
• Laxatives include hyperosmolar drugs, dietary
  fiber and related bulk-forming substances,
  emollients, stimulants, and lubricants.

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OPIOID-RELATED DRUGS

• Decrease peristalsis in the intestines.
• Include
• Difenoxin
• Diphenoxylate (Lomotil)
• Loperamide (Imodium)

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OPIOID-RELATED DRUGS

• Pharmacokinetics
• Loperamide isnt absorbed well distributed in
  the serum metabolized in the liver excreted in
  the feces.
• Pharmacodynamics
• Slow GI motility by depressing the circular and
  longitudinal muscle action in the small and large
  intestines.

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OPIOID-RELATED DRUGS

• Pharmacotherapeutics
• Used to treat acute, nonspecific diarrhea.
• Loperamide is also used to treat chronic
  diarrhea.
• Drug interactions
• May enhance the depressant effects of
  barbiturates, alcohol, narcotics, tranquilizers,
  and sedatives.

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OPIOID-RELATED DRUGS

• Adverse reactions
• GI distress

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KAOLIN PECTIN

• Locally acting OTC antidiarrheals that work by
  adsorbing irritants and soothing intestinal
  mucosa.
• Pharmacokinetics
• Arent absorbed or distributed excreted in the
  feces.

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KAOLIN PECTIN

• Pharmacodynamics
• Bind with bacteria, toxins, and other irritants
  on the intestinal mucosa.
• Pectin decreases the pH in the intestinal lumen
  which provides a soothing effect on the irritated
  mucosa.
• Pharmacotherapeutics
• Used to relieve mild to moderate diarrhea.

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KAOLIN PECTIN

• Drug interactions
• Can interfere with the absorption of digoxin or
  other drugs from the intestinal mucosa if
  administered at the same time.
• Adverse reactions
• Constipation

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HYPEROSMOLAR LAXATIVES

• Work by drawing water into the intestine
  promoting bowel distention and peristalsis.
• Include the following drugs
• Glycerin
• Lactulose
• Saline compounds

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HYPEROSMOLAR LAXATIVES

• Pharmacokinetics
• Glycerin is administered into the colon and isnt
  absorbed systemically.
• Lactulose is administered orally is minimally
  absorbed distributed in the intestine
  metabolized by bacteria in the colon excreted in
  the feces.

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HYPEROSMOLAR LAXATIVES

• Saline compounds are administered orally and
  rectally some ions are absorbed and excreted in
  the urine the unabsorbed drug is excreted in the
  feces.
• Polyethylene glycol (PEG) or GoLytely act as an
  osmotic drug but is not absorbed so it doesnt
  alter electrolyte balance.

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HYPEROSMOLAR LAXATIVES

• Pharmacodynamics
• Produce a bowel movement by drawing water into
  the intestine.
• Pharmacotherapeutics
• Glycerin is used in bowel retraining.
• Lactulose is used to treat constipation and
  decrease ammonia production and absorption from
  the intestines in liver disease.

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HYPEROSMOLAR LAXATIVES

• Saline compounds are used when prompt and
  complete bowel evacuation is required.
• Drug interactions
• Dont interact significantly with other drugs
  except for PEG.
• Adverse reactions
• Electrolyte imbalances

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DIETARY FIBER RELATED BULK-FORMING LAXATIVES

• A high fiber diet is the most natural way to
  prevent or treat constipation.
• Include the following drugs
• Methylcellulose (Citrucel)
• Polycarbophil (Fiberall)
• Psyllium hydrophilic mucilloid (Metamucil)

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DIETARY FIBER RELATED BULK-FORMING LAXATIVES

• Pharmacokinetics
• Not absorbed systemically polysaccharides in
  these drugs are converted into osmotically active
  metabolites that draw water into the colon
  excreted in the feces.
• Pharmacodynamics
• Increase stool mass and water content promoting
  peristalsis.

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DIETARY FIBER RELATED BULK-FORMING LAXATIVES

• Pharmacotherapeutics
• Used to
• Treat simple constipation.
• Aid patients recovering from acute MIs, cerebral
  aneurysms, or eye surgery who need to avoid the
  Valsalva maneuver.
• Manage patients with irritable bowel syndrome and
  diverticulosis.

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DIETARY FIBER RELATED BULK-FORMING LAXATIVES

• Drug interactions
• Decreased absorption of digoxin, warfarin, and
  salicylates if taken within two hours of these
  laxatives.
• Adverse reactions
• Gas, distention, obstruction, impaction

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EMMOLIENT LAXATIVES

• Also known as stool softeners.
• Include the calcium, potassium, and sodium salts
  of docusate.
• Pharmacokinetics
• Administered orally absorbed and excreted
  through the bile in the feces.

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EMMOLIENT LAXATIVES

• Pharmacodynamics
• Soften the stool and make bowel movements easier
  by allowing water and fats to penetrate the
  stool.
• Also stimulate electrolyte and fluid secretion
  from the intestinal mucosal cells.

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EMMOLIENT LAXATIVES

• Pharmacotherapeutics
• The drug of choice for patients who should avoid
  straining during bowel movements including those
  with
• Recent MI or cardiac surgery
• Disease of the anus or rectum
• Increased ICP
• Hernias

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EMMOLIENT LAXATIVES

• Drug interactions
• May enhance the absorption of many oral drugs,
  therefore, drugs with a narrow therapeutic index
  should be administered cautiously.
• Adverse reactions
• Seldom occur.

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STIMULANT LAXATIVES

• Also known as irritant cathartics.
• Include the following drugs
• Bisacodyl (Dulcolax)
• Cascara sagrada
• Castor oil
• Phenolphthalein (Ex-Lax)
• Senna (Senokot)

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STIMULANT LAXATIVES

• Pharmacokinetics
• Minimally absorbed metabolized in the liver
  excreted in the urine and feces.
• Pharmacodynamics
• Stimulate peristalsis and produce a bowel
  movement by irritating the intestinal mucosa or
  stimulating nerve endings of the intestinal
  smooth muscle.

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STIMULANT LAXATIVES

• Pharmacotherapeutics
• The preferred drugs for emptying the bowel before
  general surgery, endoscopic procedures, and
  radiologic procedures.
• Also used to treat constipation caused by
  prolonged bedrest, neurologic dysfunction of the
  colon, and constipating drugs such as narcotics.

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STIMULANT LAXATIVES

• Drug interactions
• Reduce the absorption of other oral drugs when
  administered at the same time.
• Adverse reactions
• Weakness, nausea, abdominal cramps, mild rectal
  and anal inflammation.

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LUBRICANT LAXATIVES

• Mineral oil is the main lubricant laxative in
  current clinical use.
• Pharmacokinetics
• Administered orally or rectally minimally
  absorbed distributed to the mesenteric lymph
  nodes, intestinal mucosa, liver, and spleen
  metabolized by the liver excreted in the feces.

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LUBRICANT LAXATIVES

• Pharmacodynamics
• Lubricates the stool and the intestinal mucosa
  and prevents water reabsorption from the lumen of
  the bowel which increases peristalsis as well.
• Pharmacotherapeutics
• Used to treat constipation and maintain soft
  stools when straining is contraindicated.

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LUBRICANT LAXATIVES

• Also used to treat patients with fecal
  impactions.
• Drug interactions
• May impair the absorption of many oral
  medications such as fat-soluble vitamins, oral
  contraceptives, and anticoagulants.
• Adverse reactions
• GI distress

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ANTIEMETIC DRUGS

• Derived from plants.
• Produce vomiting.
• Include
• Antihistamines - dimenhydrate (Dramamine),
  meclizine hydrochloride (Antivert)
• Phenothiazines - prochlorperazine (Compazine),
  promethazine hydrochloride (Phenergan)

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ANTIEMETIC DRUGS

• Serotonin receptor antagonists - ondansetron
  (Zofran) antiemetic of choice in the U.S.,
  granisetron (Kytril)
• Pharmacokinetics
• Absorbed well metabolized by the liver excreted
  in the urine and/or feces.

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ANTIEMETIC DRUGS

• Phenothiazines block the vomiting center in the
  medulla of the brain.
• Serotonin receptor antagonists block serotonin
  stimulation centrally in the chemoreceptor
  trigger zone and peripherally in the vagal nerve
  terminals, both of which stimulate vomiting.

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ANTIEMETIC DRUGS

• Pharmacotherapeutics
• Antihistamines prevent or treat motion sickness.
• Phenothiazines and serotonin receptor antagonists
  control severe nausea and vomiting post-surgery,
  viral-related, during chemotherapy, and radiation
  therapy.

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ANTIEMETIC DRUGS

• Drug interactions
• Many significant interactions and adverse
  reactions may occur, therefore, the nurse should
  always consult a drug handbook prior to
  administration.

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EMETIC DRUGS

• Used to induce vomiting in a person who has
  ingested toxic substances.
• Syrup of Ipecac is the drug of choice because it
  is the most effective and the least likely to
  cause problems.
• It has become controversial because it delays the
  use of charcoal.

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EMETIC DRUGS

• Pharmacokinetics
• Little is known about its properties.
• Vomiting occurs within 10 to 30 minutes.
• Pharmacodynamics
• Induces vomiting by stimulating the vomiting
  center located in the medulla of the brain.

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EMETIC DRUGS

• Pharmacotherapeutics
• Considered the therapy of choice for emptying the
  stomach because of its effectiveness and low
  incidence of adverse effects.
• Drug interactions rarely occur.
• Adverse reactions rarely produced.