report ko.. pharma
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Gastrointestinal
Pharmacotherapy
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Objectives
Discuss the process of acid secretion inthe gastrointestinal tract
Differentiate medications used tosuppress gastric acid secretion
Explain the role of gastrointestinal
motility in disease states
Differentiate medications used to accountfor impaired gastrointestinal motility
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Gastrointestinal tract
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Disorders of the
Esophagus and Stomach Gastroesophageal Reflux Disease (GERD)
Dyspepsia/Non-erosive reflux disease (NERD)
Esophagitis (erosive)
Peptic ulceration
H. pylori associated peptic ulcers
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Gastric Secretion
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Stomach Anatomy
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Defense Mechanisms
Lower esophageal sphincter
Secretion of gastric mucus
Stimulated by prostaglandin E2 and I2
Secretion of bicarbonate ions
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GERD
Definition: when the reflux of stomachcontents causes troublesome symptomsor complications
Diagnosis:
Presence of symptoms
Demonstration of reflux
Identification of existing damage fromreflux
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Epidemiology
44% of adults in the US experienceheartburn 1 time/month
Up to 15-18% of adults in the USexperience heartburn weekly
Heartburn or substernal burning is the
most commonly recognizedmanifestation of GERD
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Risk Factors for GERD
Obesity
Food (spicy, chocolate, peppermint)
Age
Smoking
CaffeineAlcohol
Pregnancy
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Stages of GERDStage Description Medical
Management
I (NERD) sporadic
2-3 episodes/wk
Lifestyle modification
Antacids/H2 RA asneeded
II Frequent symptoms
+/- esophagitis
PPI vs. H2RA
III Chronic, unrelenting
Immediate relapse offtherapy
Esophagealcomplications
PPI once or twice
daily
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Treatment of GERD
Decrease acidity of stomach contents
Antacids
H2 receptor antagonists
Proton pump inhibitors
Protect gastric mucosa sucralfate
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Chemically neutralize stomach acid
Base (OH)3 or CO3 + Al, Ca, or Mg
CaCO3= calcium carbonate (Tums)
Al (OH)3 + Mg (OH)2 = Maalox
Some contain simethicone (a surfactant)Al (OH)3 + Mg (OH)2 + simethicone = Mylanta
Site GI chapter
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Antacids
Mechanism of Action:
Antacid + HCl salt + water
Examples
Al(OH)3 + 3 HCl AlCl3 + 3H2O
CaCO3 + 2 HCl CaCl2 + 2H20 + CO2
Site GI chapter
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Antacids
Side Effects
Constipation (Al containing products)
Diarrhea (Mg containing products) Electrolyte imbalances
Decreases absorption of other drugs
Place in Therapy
Minor, infrequent dyspepsia
With other acid suppressants on an as neededbasis
Calcium supplementation
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H2-Receptor Antagonists
Block histamine from binding to H2receptors on parietal cell
Decrease rate of activation byhistamine decreased acid secretion
Blocks basal and bolus acid secretion Basal: continuous acid secretion Bolus: secretion in response to stimuli
(food, etc)
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H2-Receptor Antagonists
Cimetidine (Tagamet) Not used often due to drug interactions
Ranitidine (Zantac) 150-300mg by mouth twice daily
Famotidine (Pepcid)
20-40mg by mouth twice daily Nizatidine (Axid)
150-300mg by mouth twice daily
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H2-Receptor Antagonists
Side Effects
Well tolerated
Many drug interactions, esp. with HIVmedication
Tolerance can develop with long term use
Place in Therapy
As needed for minor dyspepsia
Daily to control frequent symptoms
Low dose for symptoms w/o esophagitis
High dose for symptoms w/ esophagitis
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Proton Pump Inhibitors
Most potent inhibitors of acid secretion
Decrease daily acid secretion 80-95%
Require activation by acid in stomach Irreversibly binds and inactivates the
H+/K+-ATPase
H+/K+-ATPase is the pump molecule thatsecretes acid from the parietal cell intothe lumen of the stomach
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Proton Pump Inhibitors
Drug Healing PreventionOmeprazole (Prilosec) 20-40mg daily 20mg daily
Esomeprazole (Nexium) 20-40mg daily 20mg daily
Lansoprazole (Prevacid) 15-30mg daily 15 mg daily
Pantoprazole (Protonix) 40mg daily 20-40mg daily
Rabeprazole (Aciphex) 20mg daily 20mg daily
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Proton Pump Inhibitors
Side Effects Well tolerated
Takes multiple doses to get full effect Place in Therapy
Symptomatic GERD with esophagitis
Promote healing of gastric ulcers Hypersecretory conditions
Prevent NSAID-associated gastric ulcers
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Miscellaneous
Other medications used for GERD Prostaglandin analogues (i.e. misoprostol)
Bind a EP3 receptor on parietal cells, decreasingcAMP (energy) available for H+/K+-ATPase
Sucralfate Sucrose + Al(OH)3 which forms a viscous layer on
the gastric mucosa Prevents acid from contacting mucosa
Metoclopramide Stimulates gastric motility increased
clearance of stomach acid
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Complications of GERD
Ulceration (w/ or w/o H. pylori)
Asthma exacerbations
Esophageal strictures
Adenocarcinoma
Barrett Esophagus
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H. Pylori Infection
Gram-negative rod
Not always associated with an activeulcer
Associated with gastritis, leads to: Gastric/duodenal ulcers
Gastric adenocarcinoma
Gastric B-cell lymphoma
Eradication is standard of care topromote healing of ulcer and to prevent
recurrence
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H. Pylori Infection
3 Drug Combination Proton pump inhibitor (high dose)
2 antibiotics (clarithromycin + amoxicillin ORmetronidazole
4 Drug Combination Proton pump inhibitor (high dose)
2 antibiotics (metronidazole + tetracycline ORamoxicillin OR clarithromycin)
Bismuth subsalicylate
All regimens 14 days in duration Patient compliance is difficult with intense regimens
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Acid-rebound Phenomenon
Chronic suppression of acid secretionleads to hypergastrinemia
Gastrin stimulates ECL cells to releasehistamine increased acid secretionfrom activation of histamine receptor onparietal cell
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Disorders of the Lower GI
Tract Constipation
Diarrhea
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Gastrointestinal Motility
The GI tract is in a continuous contractile,absorptive, & secretory state
Muscle, CNS, ENS (enteric nerve system),and humoral pathways control GImovement
4 phases to movement in the GI tract Peristalsis is most important, moves contents
through GI tract
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GI Motility
increased transit time
- Increased waterabsorption constipation
decreased transit time
-Decreased water andnutrient absorption diarrhea
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Constipation
Affects up to 27% of Americans
Accounts for 2.5 mil. physician visits/year
$400 million spent on OTCs annually
Definition
Unsatisfactory defecation that results ininfrequent stool, difficult stool passage, orboth
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Constipation
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Causes of Constipation
GI disorders Irritable bowel syndrome, hernia, anal
fissures Metabolic disorders
Diabetes with neuropathy, hypothyriodism
Pregnancy
Psychogenic disorders
MedicationsAnalgesics, antacids, iron preparations
.
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Treatment of Constipation
Lifestyle modifications Fiber-rich dietAdequate fluid intake
Appropriate bowel habits and training Exercise
Medications Bulk-forming laxatives
Stimulant laxatives Hyperosmotic laxatives Stool softeners
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Bulk-Forming Laxatives
3 kinds
Psyllium (Metamucil)
Methylcelluose (Citrucel) Calcium polycarbophil (Fibercon)
Increases colonic mass which triggers
peristalsis Increases water content of stool via
hydrophilic forces
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Stimulant Laxatives
Induce low-grade inflammation in the small and largeintestine Promotes accumulation of water and stimulates
motility Provides soft or semifluidstool in 6-12 hours Bisacodyl (Dulcolax)
5-15 mg by mouth daily; 10mg rectally daily (rectaladministration effective within 1 hour)
Castor Oil Senna (Senokot)
8.6mg sennosides 1-2 times per day (1-2 tabletsonce or twice daily)
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Hyperosmotic Laxatives
Osmotically mediated water retention (viacations-Al, Mg, etc) which stimulatesperistalsis
Provides wateryfecal evacuation in 1-6 hours
Magnesium hydroxide (Milk of Mag) 5-15mL by mouth four times daily
Polyethylene glycol (Miralax
) Dose used depends on level of evacuation
Sodium phosphate (Fleets Phosphosoda)
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Stool Softeners/Lubricants
Docusate (Colace) Stool softener Mixes aqueous and fatty material in the
intestinal tract, leading to increase stool watercontent
Used to prevent constipation or straining 1-2 capsules by mouth once or twice daily
Mineral Oil (Nujol)
Lubricant Coats stool and allows for easier passage 15-30mL orally as needed Causes softening and passage of stoolin 1-3
days
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Diarrhea
Prevalence of diarrhea varies in developed vs.non-developed countries
1.3 billion episodes/yr in developing countries4 million deaths
Can be associated with an infectious cause
Shigella, Salmonella, E. Coli among most common
Most diarrhea is self-limiting
Defined as an increase in stool frequency orwater content
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Diarrhea
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Opioid Derivatives
Bind the -receptor on enteric nerves,epithelium, and muscle
Decrease GI motility Increase absorption of water from the bowel
Diphenoxylate (Lomotil)
5mg by mouth 4 times daily (max 20mg/day)
Loperamide (Immodium)
4mg by mouth first, then 2mg by mouth aftereach loose stool (max 16mg/day)
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Adsorbents
Non-selectively absorbs intestinal fluid
Regulates stool texture and viscosity
Bind bacterial toxins and bile saltsAttapulgite (Kaopectate)
30-120mL after each loose stool
Can bind other medications, mustspace out from others by 2 to 3 hours
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Bismuth Salicylate
Anti-secretory, anti-inflammatory,antimicrobial effects
Used for the prevention and treatmentof travelers diarrhea
PeptoBismol
30mL (2 tabs) every hour as needed (upto 8 times/day)
Excessive use can lead to salicylatepoisioning
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Probiotics
Replaces normal colonic microflora
Restores intestinal function and suppresses thegrowth of pathogenic bacteria
Lactobacillus acidophilus (Lactinex)
2 tabs or 1 packet of granules 3-4 times daily
Dairy Products
200-400 grams of lactose
Special lactobacillus containing yogurts
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Conclusion
Approximately 1/3 of your patients willbe taking a medication for GERD
Approximately of your patients willbe taking a medication for constipation
GERD, constipation, and diarrheaaffect a patients quality of life
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Questions?
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