H2 antagonist.pdf

H2 antagonists

1. UNIT-1
H2 ANTAGONIST
LECTUREBY
DR. JASMINECHAUDHARY
ASSOCIATEPROFESSOR

2. INTRODUCTION
Also known as antiulcer and antisecretory.
Approximately2Lofacidissecretedbyparietalcellsinstomach
informofhydrochloricacid.Thisacidishelpfulinkillingbacteria
andalsoaidindigestionbysolubilizingfood.
SubstancesthatstimulateacidsecretionareAcetylcholine,
Histamine,gastrinetc.andsubstancethatregulateorinhibitacid
secretionissomatostatin.

3. ExcessiveHClsecretionleadstodamageofmucus
membraneleadingtoulcer.
Ulcerisalsocausedbymicro-organismHelicobacterpyroli
andbyfrequentusesofNSAIDs.
Thereforeinhibitionofgastricsecretionisoneofthe
therapeutictargetfortreatmentofulcerdisease.

4. Strategies for treatment of ulcers
1.Antacids(Aluminiumandmagnesiumhydroxide
gel).
2.Targetingmuscarinicreceptorwithmuscarinic
antagonistlikedicyclomine.
3.H2 receptor antagonist (Cimetidine,
ranitidine)
4.Antimicrobialtherapyincombinationwith
antisecretorydrugsforH.pyroliinfections
5.Mucosalprotectiveagents:Sucraflate
6.Protonpumpinhibitors:Omeprazole

5. H2 RECEPTOR ANTAGONISTS
Block histamine to bind to H2 receptor and thus antagonise
its action.
TheprototypeofthisclasswasGuanylhistaminewhichwas
partialagonist.Modificationsinitsstructureleadsto
discoveryoffirstselectiveH2antagonistBurimamidebut
itwashavingverypoororalabsorption.
Toimproveoralabsorptionmethylgroupwasintroducedon
imidazoleringandsulphurisintroducedinsidechain
leadingtodiscoveryofMetiamidebutitcauseskidney
damage

6. H2 RECEPTOR ANTAGONISTS
Toreducethissideeffect,thionegroupwasreplacedby
cyanoiminogroupgivingCimetidine.
CimetidinewasthefirstpotentH2antagonistdevoid
ofthissideeffect(kidneydamage).
Lateritwasinvestigatedthatwhetherimidazoleringis
essentialforactivityornotsoderivativeswithother
heterocyclicringweresynthesizedanditwasobservedthat
imidazoleringisnotessentialforactivity.Twonewpotent
compounds(RanitidineandFamotidine)havingmore
activitythancimetidinewerediscovered.

7. Ranitidineconsistsoffuranringinsteadofimidazole
ringandisfivetimemorepotentthancimetidine.
Famotidineconsistsofthiazoleringandis20times
morepotentthancimetidine.

8. Burimamide(Poor
oral absorption)
Metiamide
(Kidney damage)
Cimetidine
Ranitidine Famotidine

9. H2antagonistsarehighlypolaranddon’tcrossBBB
therefore,don’tcausesedationassideeffect.
ThefirstbrainpenetratingH2blockerisZolantidine.

10. MODEOFACTION

11. MODEOF ACTION
On parietal cells, 3 receptors are found to mediate HCl
secretion.
Cholinergic agonist/ Acetyl choline binds to muscarinic
receptor
Gastrinbinds to gastrin receptor
Histaminebindstohistaminereceptor
In parietal cells, carbonic acid is produced from CO2 and
water which gets hydrolysed to H+ ions and HCO3-ions
with help of enzyme carbonic anhydrase (CA)

12. H+ionsareexchangedwithK+ionsthroughH+/K+
ATPasepump.
HCO3-ionsareexchangedwithCl-ions(fromCl-
channels)
BothH+ionsandCl-ionscombinestoformHCl.
H2antagonistblockhistaminetobindtoreceptor
thereforeinhibitingreleaseofgastricacid.

13. Uses
In treatment of peptic ulcer.
In Heart burn
Dyspepsia
InZollingerEllisonsyndrome (pathological
hypersecretorystateduetotumorsinsmallintestine
resultinginexcessiveproductionofacid.
SideEffects
Hypotension
Headache
Tiredness
Diarrhea/Constipation

14. PROTONPUMPINHIBITORS
DrugswhichdirectlyinhibitinH+/K+ATPasepump
andthusinhibitHClreleasearecalledprotonpump
inhibitors.
Examples includeOmeprazole,Pantoprazole,
Rabeprazole,Lansoprazole

16. USES
Totreatsymptoms ofgastroesophagealreflux
disease(GERD)andotherconditionscausedbyexcess
stomachacid.Itisalsousedtopromotehealingoferosive
esophagitis(damagetoesophaguscausedbystomachacid).
Omeprazolemayalsobegiventogetherwithantibioticsto
treatgastriculcercausedbyinfectionwithHelicobacter
pylori(H.pylori).
Inheartburnsalso.
Sideeffectsincludeheadache,dizziness,nausea,gas,
bloating.