gastrointestinalpharmacotherapypptfinal-12639285176985-phpapp01

8/13/2019 gastrointestinalpharmacotherapypptfinal-12639285176985-phpapp01

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Gastrointestinal

PharmacotherapySarah Nelson, Pharm.D.

March 3, 2009


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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

http://www.nationmaster.com/encyclopedia/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

Ali, T. Miner, P. New Developments in gastroesophageal reflux disease diagnosis and therapy.Curr Opin in Gastroenterology. 2008;24:502-508


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Stomach Anatomy

https://reader010.{domain}/reader010/html5/0624/5b2e88bde21ff/5b2e88c094d33.jpg


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Defense Mechanisms

Lower esophageal sphincter

Secretion of gastric mucus

Stimulated by prostaglandin E2and I2

Secretion of bicarbonate ions

Brunton, Laurence. Goodman & Gillmans The Pharmacological Basis of Therapeutics.11thEdition. USA; McGraw-Hill Company, 2006.


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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

Ali, T. Miner, P. New Developments in gastroesophageal reflux disease diagnosis and therapy.Curr Opin in Gastroenterology. 2008;24:502-508


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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

Shaheen, N., Ransohoff, D.F. Gastroesophageal Reflux, Barrett Esophagus, and Esophageal Cancer: Scientific Review. JAMA. 2002;287(15):1972-1981


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Risk Factors for GERD

Obesity

Food (spicy, chocolate, peppermint)

Age

Smoking

CaffeineAlcohol

Pregnancy

Dipiro, Joseph et al. Pharmacotherapy: A Pathophysiologic Approach. 6thEdition. USA; McGraw-Hill Company, 2005.


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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 relapseoff therapy

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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Antacids

Chemically neutralize stomach acid

Base (OH)3or 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

Site GI chapter


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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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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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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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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

Site GI chapter


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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 EP3receptor on parietal cells, decreasingcAMP (energy) available for H+/K+-ATPase

Sucralfate Sucrose + Al(OH)3which forms a viscous layer on

the gastric mucosa Prevents acid from contacting mucosa

Metoclopramide Stimulates gastric motility increased

clearance of stomach acidSite GI chapter


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Complications of GERD

Ulceration (w/ or w/o H. pylori)

Asthma exacerbations

Esophageal strictures

Adenocarcinoma

Barrett Esophagus

Shaheen, N., Ransohoff, D.F. Gastroesophageal Reflux, Barret Esophagus, and Esophageal Cancer: Scientific Revies. JAMA. 2002;287(15):1972-1981Dougherty, R., Fahy, J. Acute exacerbations of asthma: epidemiology, biology and the exacerbation-prone phenotype.Clinical and Experimental Allergy.2009;39(2):193-202


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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

recurrenceBrunton, Laurence. Goodman & Gillmans The Pharmacological Basis of Therapeutics.11thEdition. USA; McGraw-Hill Company, 2006.


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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

https://reader010.{domain}/reader010/html5/0624/5b2e88bde21ff/5b2e88cc0a0cc.jpg

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

Cash, B. et al. Update on the Management of Adults with Chronic Idiopathic Constipation.The Journal of Family Practice. 2007;56(6):S13-20


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Constipation

http://www.helpfulhealthtips.com/Images/C/constipation1.jpg


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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 forcesBrunton, Laurence. Goodman & Gillmans The Pharmacological Basis of Therapeutics.11thEdition. USA; McGraw-Hill Company, 2006.


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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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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

http://www.ghi.com/WebMD/topics/diarrhea.jpg


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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)

Site GI chapter



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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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