Drugs g Affecting gthe GastrointestinalSystem

CaiyingYE DepartmentofPharmacology, SchoolofBasicMedicine, PekingUnionMedicalCollege

DrugsAffectingthe GastrointestinalSystem
Antiulcerants Digestives Antiemetics Purgatives Antidiarrheals Cholagogues

P ti Ulcers Peptic Ul
Common C di disease incidence i id rate: t 10%~12%. 10%~12% Pathogenesis of ulcers
A Aggressive i Factors F t Defensive D f i Factors F t

Acid,pepsin ,p p Bilesalts Drugs(NSAIDs) H.pylori

Mucus,bicarbonatelayer Bloodflow,cellrenewal Prostaglandins P l di Phospholipid Freeradicalscavengers

Gastroesophageal RefluxDisease
Mostcommondisorderoftheesophagus p g Characterizedbyregurgitationofgastriccontents intotheesophagus Occursmostoftenafterameal Worsewhenrecumbent Causedbyincompetentloweresophagealsphincter Foodsthatcauserelaxationinclude:caffeine,fats, chocolate cigarrette smoking, chocolate, smoking gastricdistentionand medications(betaadrenergicblockers,calcium channelblockers,nitrates) )

Gastroesophageal RefluxDisease
Backflow of stomach acid into the esophagus Esophagus is not equipped to handle stomach acid => scaring Usual symptom is heartburn, an uncomfortable burning sensation behind the breastbone (MI often mistaken i t k for f GERD !) More severe symptoms: symptoms: difficulty swallowing, chest pain Reflux into the throat can cause sore throat

Gastroesophageal RefluxDisease
Complications include esophageal erosions, esophageal ulcer and narrowing of the esophagus (esophageal stricture) In some patients, the normal esophageal lining or epithelium may be replaced with abnormal (Barrett's) (B tt' ) epithelium. epithelium ith li . This Thi condition diti (B (Barrett's tt' esophagus) has been linked to cancer of the esophagus. esophagus . Primary treatment : proton pump inhibitors

PepticUlcers
Therapy Purpose Therapyisdirectedat enhancing h i host h tdefense d f or eliminatingaggressive factors;i.e., i e H. H pylori. pylori

DrugsUsedinPepticUlcers
Antacids Inhibitorsofgastricacidproduction H2receptorantagonists Protonpumpinhibitors Muscarinicantagonists Gastrinreceptorantagonist MucosalProtectants AntiHelicobacterpylori.drugs

Acid Pump

DrugsUsedinPepticUlcers
Antacids

aluminumhydroxide magnesiumhydroxide
H2

receptorantagonists

cimetidine ranitidine
Muscarinicantagonists g

atropine

DrugsUsedinPepticUlcers
Protonpumpinhibitors omeprazole Gastrinreceptorantagonist proglumide MucosalProtectants misoprostol AntiHelicobacterpylori.Drugs antibiotics

Antacids
General characteristics Antacids are weak bases that are taken orally and that partially neutralize gastric acid and reduce pepsin activity. Antacids reduce the pain associated with ulcers and may promote healing. High doses are required for healing: 40 mEq of base seven times daily.

Antacids
Magnesium hydroxide (constipation) Aluminum Al i hydroxide h d id Calciumcarbonate Sodiumbicarbonate

H2receptorantagonists
Mechanism of action Competitively block the histamine (H2) receptor of acidproducing parietal cells rendering cells less responsive to not only histamine but also to the stimulation of acetylcholine and gastrin. Also up to 90% inhibition of vagal stimulated and gastrin stimulated acid secretion. p inhibition has not been shown complete

H2receptorantagonists
FourFDAapproved: Cimetidine Tagamet g Ranitidine Zantac F Famotidine idi Pepcid P id Nizatidine Axid Roxatidine

H2receptorantagonists
Therapeutic effects: Promote the healing g of g gastric and duodenal ulcers Gastroesophageal reflux dz [GERD] Upper GI bleed [GIB] May be effective in stress ulcers & peptic esophagitis

H2receptorantagonists
Sideeffect: Overalllow<3% CNS:<1%total headache,lethargy,confusion,depression hallucinations ENDOCRINE Impotenceincreasedprolactingynecomastia HEMATHOLOGY Thrombocytopenia

Muscarinicantagonists
Atropine p BlocktheM1classreceptors reduceacidproduction gastrointestinalspasm p abolishg relativelyunpopular asafirstchoicebecauseof highincidenceofanticholinergicsideeffects (drymouthandblurredvision)

P Proton pumpi inhibitors hibi

H+,K+ H+ K+ATPase(ProtonPump)inhibitor Irreversibleinhibition Mustsynthesizenewenzyme Longduration Omeprazole (Prilosec) Lansoprazole (Prevacid) Pantoprazole Rabeprazole

MechanismofAction

Omeprazole(Losec) Losec)
IrreversiblybindstoH+/K+ATPase production&secrection PreventsH+ionp Blockallacidsecretion=achlorhydriatoreturnto normalmustsynthesizenewH+/K+ATPase InhibitH.pylori

Omeprazole(Losec )
Therapeutic uses Gastroesophageal reflux dz [GERD] Peptic ulcer Infection with H. H pylori plus Upper GI bleed [GIB]

Omeprazole Lansoprazole

Pantoprazole

MucosalProtectiveAgents

Misoprostol
Acongenerof fprostaglandin t l di E1 PGs: inhibit i hibi gastric i acid idsecretion i exhibitcytoprotectiveactivity enhancelocalproductionofmucusor bicarbonate promotelocalcellregeneration helptomaintainmucosalbloodflow

Misoprostol
Misoprostolisapprovedfor useinpatientstakingNASIDs whoareatriskforgastric ulcers Misoprostolproducesdiarrhea andstimulationofuterine contraction.

 Sucralfate S lf t
cytoprotective agent Thoughttopossible bi dt bind toth theulcer l and df formaprotective t ti barrier b i betweenthemucosaandgastricacid,pepsin andbilesalts;andstimulatingprostaglandin synthesis stressulcerations&PUD inhibitH.pylori Cannotbegivenwithanantacid, antacid H2RAorPPI maybindotherdrugsandpreventtheir p absorption

 Bismuth(PeptoBismol)
inhibitp pepsin p activity y inhibitH.pylori Tripotassium dicitratobismuthate isabismuth chelate effectiveinhealinggastricand duodenalulcers ColloidalBismuthSubcitrate(CBS)isusedin themanagementofgastricandduodenal ulcers,andincombinationwithtwo antibacterials fortheeradicationofH.pylori.

AgentsUsedininfectionof HelicobacterPylori
Helicobacterpylori(H.pylori)

AgentsUsed din i infection i f i of f HelicobacterPylori

AimedateliminatingH.pylori Gentamicin Amotriptyline (Amoxil) Clarithromycin Tetracycline (AchromycinV) Metronidazole (Flagyl)

A AgentsU Used di ini infection f i of fH. H pylori l i

TripleTherapy: (A)1st linetiple therapy(1+2) 1 Amoxicillin 1. A i illi 500mg+Metronidazole M t id l 250mgqid, id 2 wks 2 Oneofthefollowingsfor6wks: 2. Colloidalbismuth120mg Cimetidine Ci tidi 400mg Ranitidine150mg Famotidine idi 20mg

A AgentsU Used di ini infection f i of fH. H pylori l i

Triple T i l Th Therapy: (B)2nd linetripletherapy(1+2) 1. Clarithromycin l h 500mgbid b d+Omeprazole l 20mgbid, bd for1wk 2 PPIorH2antagonist 2. t i treceptor t th therapy

Before 1970

Antacids

1970~

H2receptorantagonists

Protonpumpinhibitors

1980~ 1990~

Protonpumpinhibitors AgentsUsedininfection of fHelicobacter H li b t Pylori P l i

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