PEPTIC ULCER.ppt

Pharmacology

2. PepticUlcersareopensoresthatdevelopontheinsideliningofyour
stomachandtheupperportionofyoursmallintestine.Themostcommon
symptomofaulcerispain.
Others types of Ulcers
Esophageal ulcers:ulcersthat develop inside the
esophagus
Gastric ulcersthat occur on the inside of the stomach
Duodenal ulcersthat occur on the inside of the upper
portion of your small intestine (duodenum)

3. Imbalance between aggressive & protective factors
Aggressive factors
Gastric acid
Proteolyticenzyme
Ethanol ingestion,
smoking
Duodenal reflux of bile
Ischemia, hypoxia,
H. pylori infection
NSAIDs.
Protective factors
Mucosal layer
Bicarbonate
secretion
Prostaglandins
Blood flow
Growth factors
Cell renewal
IMBALANCE

4. E
T
I
O
L
O
G
Y
Helicobacter pylori
Smoking
Alcohol
NSAID
Stomach cancer
Stress

7. S
Y
M
P
T
O
M
S
Blood Vomiting
Dark Stool
Anaemia
Heart Burning
Acid Reflux
Nausea and Vomiting
Weight Loss
Bloating
Less interest in eating
Due to pain
Stomach Pain

8. Diagnosis
LaboratorytestsforH.pylori-H.pyloritestusingablood,stoolorbreathtest.The
breathtestisthemostaccurate.Bloodtestsaregenerallyinaccurateandshouldnot
beroutinelyused.
Breath test
Youdrinkoreatsomethingthatcontainsradioactivecarbon.H.pyloribreaksdownthe
substanceinyourstomach.Later,youblowintoabag,whichisthensealed.Ifyou're
infectedwithH.pylori,yourbreathsamplewillcontaintheradioactivecarboninthe
formofcarbondioxide
Endoscopy
Doctormayuseascopetoexamineyourupperdigestivesystem(endoscopy).During
endoscopy,yourdoctorpassesahollowtubeequippedwithalens(endoscope)down
yourthroatandintoyouresophagus,stomachandsmallintestine.Usingthe
endoscope,yourdoctorlooksforulcers.

9. Biopsy
Ifyourdoctordetectsanulcer,smalltissuesamples(biopsy)maybe
removedforexaminationinalab.AbiopsycanalsoidentifywhetherH.
pyloriisinyourstomachliningoranytypesofCancer.
Upper gastrointestinal series
Sometimescalledabariumswallow,thisseriesofX-raysofyourupper
digestivesystemcreatesimagesofyouresophagus,stomachandsmall
intestine.DuringtheX-ray,youswallowawhiteliquid(containing
barium)thatcoatsyourdigestivetractandmakesanulcermorevisible.

10. C
L
A
S
S
I
F
I
C
A
T
I
O
N
ProtonpumpInhibitor–Pantoprazole,
Rabiprazole,Lansoprazole,Omeprazole.
HistamineReceptorAntagonist–
Cimetidine,Ranitidine,Famotidine.
Prostaglandin Analogue –
Misoprostol.
Ulcer protective –Sucralfate,
Bismuth. Chelate.
Antacid
Suppressacidproduction–Anti
cholinergiccompound–Atropine,
Dycyclomine,Oxyphenonium.
Antibiotics –Amoxicillin,
Clarithromycine
Systemic -NaHCO
3, CaCO
3.
Non systemic -Al(OH)
3,Mg(OH)
2

11. Anti cholinergic
Atropine,
Dycyclomine,
Oxyphenonium

12. Proton Pump Inhibitors
PPIsreducetheproductionofacidbythestomach.Theyworkbyirreversiblyblocking
anenzymecalledH+/K+ATPasewhichcontrolsacidproduction.Thisenzymeisalso
knownastheprotonpumpandisfoundintheparietalcellsofthestomachwall.
Omeprazole
It is the prototype member of substituted benzimidazoles which inhibit the final
common step in gastric acid secretion.
Theonlysignificantpharmacologicalactionofomeprazoleisdosedependent
suppressionofgastricacidsecretion;withoutanticholinergicorH2blockingaction
Itisapowerfulinhibitorofgastricacid:cantotallyabolishHClsecretion,bothresting
aswellasthatstimulatedbyfoodoranyofthesecretagogues,withoutmucheffecton
pepsin,intrinsicfactor,juicevolumeandgastricmotility.
OmeprazoleisinactiveatneutralpH,butatpH<5itrearrangestotwocharged
cationicforms(asulphenicacidandasulphenamideconfigurations)thatreact
covalentlywithSHgroupsoftheH+K+ATPaseenzymeandinactivateitirreversibly,

13. After absorption if diffusion and concentrate in parietal cell and then in acidic pH of
canaliculi
Binds tighlycovalently with enzyme of parietal cell confer high degree of selectivity
Acid secretion resumes only when new H+K+ATPasemolecules are synthesized
PHARMACOKINETIC:
AllPPIsareadministeredentericcoated,Oralbioavailabilityis50%duetoacidlability,
Foodinterfereswithabsorption,Shouldbetaken1hourpriortomeal,Highlyplasma
proteinbinding,MetabolisedbyCYP2C19andCYP3A4,Plasmat1/2is1hour,
Metabolitesareexcretedinurine.
ADVERSE EFFECT
DiarrhoeaHeadacheAbdominal painNausea

14. THERAPEUTIC USES:
Treatment of Peptic ulcer
Zollinger-Ellison syndrome
Gastroesophagealreflux disease (GERD):
Treatment of Stress ulcers
Bleeding peptic ulcer
Somewhat more potent than omeprazole but similar in propertiesLansoprazole
Pantoprazole It is similar in potency and clinical efficacy to omeprazole
S-Pantoprazole It is the active single enantiomer, twice as potent as the racemate.
Rabeprazole This newer PPI is claimed to cause fastest acid suppression
DexrabeprazoleIt is the active dextro-isomer of rabeprazole; produces similar acid suppression
at half the dose

15. ANTI-HISTAMINE:
Firstclassofhighlyeffectivedrugsforacidpepticdiseasebutsurpassedbyproton
pumpinhibitorsCimetidinewasthefirsttointroduceinthemarketanddescribedas
prototype
PHARMACOLOGICAL ACTION:
H2 blockade: Blockhistamine induced gastric secretion, cardiac stimulation,
uterine relaxation
No effect on H1 responses because they are selective
GASTRIC SECREATION:Marked inhibition of gastric secretion
Secretory response to not only histamine but also Ach, gastrin, insulin, alcohol, food
are attenuated
The volume, pepsin content and intrinsic factor secretion are reduced
They don’t have any direct action on gastric or oesophagealmotility
They attenuate fall in BP due to histamine, especially the late phase response
seen with high doses.

16. PHARMACOKINETIC:
Adequatelyabsorbedorally,Bioavailabilityis60-80%,Undergoesfirstpass
metabolism,Crossesplacentaandreachesmilk,About2/3ofdoseisexcreted
unchangedinurine/bile,Eliminationt1/2is2-3hr,Dosereductionisneededinrenal
failure.
ADVERSE EFFECT:
Dry Mouth DiarrhoeaFatigueHeadacheInsomnia
VomitingBowel upset
Therapeutic uses:
Peptic Ulcer. Duodenal ulcer, Gastric ulcer, Stress ulcer, GERD, Zollingerellison
syndrome ,Prophylaxis of aspiration pneumonia.

17. CimetidineinhibitsseveralcytochromeP-450isoenzymesandreduceshepaticbloodflow.It
inhibitsthemetabolismofmanydrugssothattheycanaccumulatetotoxiclevels,e.g.
theophylline,phenytoin,carbamazepine,phenobarbitone,sulfonylureas,metronidazole,
warfarin,imipramine,lidocaine,nifedipine,quinidine.
Interactions
FamotidineA thiazolering containing H2 blocker which binds tightly to H2 receptors and
exhibits longer duration of action despite an elimination t½ of 2.5–3.5 hr.
It is 5–8 times more potent than ranitidine.
BecauseoflowaffinityforcytochromeP450andthelowdose,drugmetabolismmodifying
propensityisminimal
Theoralbioavailabilityoffamotidineis40–50%,anditisexcretedbythekidney,70%
intheunchangedform.
Onlyheadache,dizziness,bowelupset,rarelydisorientationandrashhavebeen
reported.
IthasbeenconsideredmoresuitableforZEsyndromeandforpreventionof
aspirationpneumonia.

18. MISOPROSTAL:
MisoprostolisasyntheticprostaglandinE1analogthatstimulates
prostaglandinE1receptorsonparietalcellsinthestomachtoreduce
gastricacidsecretion.Mucusandbicarbonatesecretionarealso
increasedalongwiththickeningofthemucosalbilayersothemucosa
cangeneratenewcells
Adverse Effect: sedation, tremor, convulsions, dyspnea, abdominal pain,
diarrhea, fever, palpitations, hypotension, and bradycardia
Misoprostol(methyl-PGE1ester)isalongeractingsyntheticPGE1
derivativewhichinhibitsacidoutputdosedependently.

19. ANTACIDS
Antacidsareaclassofmedicinesthatneutralizeacidinthestomach.Theycontainingredients
suchasaluminum,calcium,magnesium,orsodiumbicarbonatewhichactasbases(alkalis)to
counteractstomachacidandmakeitspHmoreneutral.
Systemic Antacids
SodiumbicarbonateItiswatersoluble,actsinstantaneously,butthedurationofactionisshort.
Itisapotentneutralizer(1g→12mEqHCl),pHmayriseabove7.However,
ithasseveraldemerits:
Absorbed systemically: large doses will induce alkalosis. (b) Produces CO2 in stomach →
distention, discomfort, belching, risk of ulcer perforation. (c) Acid rebound occurs, but is usually
short lasting. (d) Increases Na+ load: may worsen edema and CHF
Use of sod. bicarbonate is restricted to casual treatment of heartburn

20. NonsystemicAntacids
Theseareinsolubleandpoorlyabsorbedbasiccompounds;reactinstomachtoformthe
correspondingchloridesalt.Thechloridesaltagainreactswiththeintestinalbicarbonatesothat
HCO3¯isnotsparedforabsorption—noacid-basedisturbanceoccurs.
Antacid combinations
A combination of two or more antacids is frequently used. These may be superior to any single
agent on the following accounts:
(a) Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting components yield prompt as well as
sustained effect.
(b) Mag. salts are laxative, while alum. salts are constipating: combination may annul each
other’s action and bowel movement may be least affected.
(c) Gastric emptying is least affected; while alum. salts tend to delay it, mag./cal. salts tend to
hasten it.
(d) Dose of individual components is reduced; systemic toxicity (dependent on fractional
absorption) is minimized.

21. ByraisinggastricpHandbyformingcomplexes,thenon-absorbable
antacidsdecreasetheabsorptionofmanydrugs,especially
tetracyclines,ironsalts,fluoroquinolones,ketoconazole,H2blockers,
diazepam,phenothiazines,indomethacin,phenytoin,isoniazid,
ethambutolandnitrofurantoin.
Drug interactions
Therapeutic Uses
Thismedicationisusedtotreatthesymptomsoftoomuchstomach
acidsuchasstomachupset,heartburn,andacidindigestion.Itisalso
usedtorelievesymptomsofextragassuchasbelching,bloating,and
feelingsofpressure/discomfortinthestomach/gut.

22. ULCER PROTECTIVES Sucralfate
Studiesinbothhumansandanimalshaveindicatedthatsucralfateformsacomplexthatbinds
toprotein-richexudatefoundonthesurfaceofulcers.Itbindstoalbuminand
fibrinogenpreventingbloodclotlysisbystomachacid(hydrochloricacid).Sucralfateincreases
thetissuelevelsoffibroblastgrowthfactorsandepidermalgrowthfactors,leadingtoan
increaseinprostaglandinsatthegastrointestinaltractlining,whichpromotethehealingof
gastrointestinalulcers
Sucralfate-albuminfilmprovidesabarrieragainsttheentryofhydrogenions,whicharea
componentofgastricacid
In humans, sucralfate, given at therapeutic doses for ulcers, decreases pepsin activity in gastric
fluids by 32%
Surface proteins at ulcer base are precipitated, together with which it acts as a physical barrier
preventing acid, pepsin and bile from coming in contact with the ulcer base.
Side effects are few; constipation is reported by 2% patients. It has potential for inducing
hypophosphatemia by binding phosphate ions in the intestine. Dry mouth and nausea are
infrequent.
Other uses Bile reflux, gastritis and prophylaxis of stress ulcers.
InteractionsSucralfateadsorbsmanydrugsandinterfereswiththeabsorptionoftetracyclines,
fluoroquinolones,cimetidine,phenytoinanddigoxin.Antacidsgivenconcurrentlyreducethe
efficacyofsucralfate.

23. Colloidal bismuth subcitrate(CBS; Tripotassiumdicitratobismuthate)
Precipitates at pH < 5. It is not an antacid but heals 60% ulcers at 4 weeks and 80–90%
at 8 weeks. The mechanism of action of CBS is not clear; probabilities are:
• May increase gastric mucosal PGE2, mucus and HCO3¯ production.
• May precipitate mucus glycoproteins and coat the ulcer base.
• May detach and inhibit H.pyloridirectly.
GastritisandnonulcerdyspepsiaassociatedwithH.pyloriarealsoimprovedbyCBS.
TheregimenforCBSis120mg(asBi2O3)taken½hrbefore3majormealsandat
bedtimefor4–8weeks.Milkandantacidsshouldnotbetakenconcomitantly
MostoftheingestedCBSpassesinthefaeces.Smallamountsabsorbedareexcretedin
urine.Sideeffectsarediarrhoea,headacheanddizziness.

24. ANTI-HELICOBACTER PYLORI DRUGS
H. pylori is a gram negative bacillus uniquely adapted to survival in the hostile
environment of stomach.
Amoxicillin
Amoxicillincompetitivelyinhibitspenicillin-bindingprotein1andotherhighmolecular
weightpenicillinbindingproteins.Penicillinbindproteinsareresponsiblefor
glycosyltransferaseandtranspeptidasereactionsthatleadtocross-linkingofD-alanine
andD-asparticacidinbacterialcellwalls.Withouttheactionofpenicillinbinding
proteins,bacteriaupregulateautolyticenzymesandareunabletobuildandrepairthe
cellwall,leadingtobacteriocidalaction
overdose may present with hematuria, oliguria, abdominal pain, acute renal failure, vomiting,
diarrhea, rash, hyperactivity, and drowsiness

25. Clarithromycin
Clarithromycinisfirstmetabolizedto14-OHclarithromycin,whichisactiveandworks
synergisticallywithitsparentcompound.Likeothermacrolides,itthenpenetratesbacteriacell
wallandreversiblybindstodomainVofthe23SribosomalRNAofthe50Ssubunitofthe
bacterialribosome,blockingtranslocationofaminoacyltransfer-RNAandpolypeptidesynthesis.
ClarithromycinalsoinhibitsthehepaticmicrosomalCYP3A4isoenzymeandP-glycoprotein,an
energy-dependentdrugeffluxpump.
Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal
discomfort. Transient hearing loss with high doses has been observed.
Metronidazole
Metronidazolebindsdeoxyribonucleicacidandelectron-transportproteinsoforganisms,
blockingnucleicacidsynthesis.Afteradministration,metronidazoleenterscellsbypassive
diffusion.Followingthis,ferredoxinorflavodoxinreduceitsnitrogrouptonitroradicals.The
redoxpotentialoftheelectrontransportportionsofanaerobicormicroaerophilic
microorganismsrendersmetronidazoleselectivetotheseorganisms,whichcausenitrogroup
reduction,leadingtotheproductionoftoxicmetabolites.TheseincludeN-(2-hydroxyethyl)
oxamicacidandacetamide,whichmaydamageDNAofreplicatingorganisms
Overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-
like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric
discomfort, and vertigo

26. NEWER DRUGS Potassium-competitive Acid Blockers
Potassium-competitive acid blockers (P-CABs) share the same final mechanism of action
Inhibits gastric H+/K+ -ATPase in a K+ competitive but reversible mechanism
Do not require prior proton pump activation to achieve their antisecretoryeffect.
Exhibit an early onset of acid-secretion inhibition due to rapid rise in peak plasma
concentration.
Linaprazan, Soraprazan, Revaprazan
MUCOSAL PROTECTANTS
Rebamipide
An amino acid derivative of 2-(1H)-quinolinonewith an anti-inflamatoryfunction and
thus may be effective as an esophageal mucosal protectant
TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXTION REDUCERS
Itisthemainmechanismofgastroesophagealreflux,bothacidicandnonacidic,accountingfor
allrefluxepisodesinhealthysubjectsandthemajorityofrefluxepisodesinGERDpatients
Cannabinoid Receptor-agonists-Rimonabant
Cholecystokinin/Gastrin Receptor antagonist-Spiroglumide, itriglumideand loxiglumide.

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Companion website: www.ataglanceseries.com/pharmacology

31. THANK YOU