Antacids

2. ☆ keywords
▪ Gastric acid
Gastric acid, gastric juice, or stomach acid, is a digestive fluid formed within
the stomach lining. It is Composed of water, HCl, KCl & NaCl.
Gastric acid plays a key role in digestion of proteins by activating digestive
enzymes, which together break down the long chains of amino acids of proteins.
▪ Parietal cell
The stomach wall contains 4 types of cell. Among them, Parietal cells are the
oxyntic cells that secret HCl.
4 types of receptors have been identified on the parietal cell - receptors for
gastrin, acetylcholine & histamine ion channels ; whose activation leads to
stimulation of acid secretion,
& receptors for prostaglandins ; whose activation leads to inhibition of acid
secretion.

3. ▪ Gastrin
Gastrin is a peptide hormone secreted from the G-cell of the stomach.
Gastrin stimulates the secretion of gastric acid by binding with the
Cholecystokinie receptor(CCK2) receptor in the parietal cells.
▪ Histamine
Histamine is an autocoids that act as a local hormone, secreted from the the
enterochromaffin-like cells (ECL cells) of the lining of stomach.
Histamine stimulates the secretion of gastric acid by binding with the Histamine
H2 receptor in the parietal cells.
▪ Acetycholine
Acetylcholine is a neurotransmitter, or a chemical messenger secreted by the
cholinergic nerve fibres of brain.
Acetycholine stimulates the secretion of gastric acid by binding with the
Cholinergic /Muscarinic receptor (M3) in the parietal cells.

5. ☆ Mechanism of gastric acid secretion
• Parietal cells containan extensive secretory network, called canaliculi from
which the "HCl" is secreted into the lumen of the stomach. H2O & CO2 are
present in cytoplasm of parietal cell. They spontaneously bind & form
H2CO3.
• When stimulated, H2CO3 inside the parietal cell becomes dissociated into
H+ & HCO3−. The H+ is then actively secreted into the canaliculi in
exchange for K+, via the H+K+ATPase(proton pump).
• On the other hand, HCO3−is transported out of the cell with a transporter
protrin in exchange for Cl- ion, which enters the cell. This Cl- ion is then
secreted into the canaliculi via the chloride channel, giving a strong
solution of HCl in the canaliculus.
• Water passes into the canaliculi by osmosis because of extra ions secreted
into the canaliculi. Thus, the final secretion from the canaliculi contains
water, HCl, KCl & small amount of NaCl.

7. ☆ Peptic ulcer
• Peptic ulcers are sores that develop in the lining of the stomach, lower
esophagus, or small intestine. They’re usually formed as a result of
inflammation caused by the Helicobacter pylori bacteria.
• The stomachhas a layer of mucus that is designed to protect it from
stomach acid. H. pylori attack this mucus lining & weakens the protective
mucous coating of the stomach & duodenum, thus allowing acid to get
through to the sensitive lining beneath. Both the acid & the bacteria
irritate the lining & cause a sore or ulcer.
• There are 3 types of peptic ulcers:
1. Gastric ulcers(Gastritis):ulcers that develop inside the stomach
2. Esophagealulcers: ulcers that develop inside the esophagus
3. Duodenal ulcers: ulcers that develop in the upper section of the small
intestines, called the duodenum.

8. Causes :
Smoking, drinking too much alcohol, radiation therapy , stomachcancer,
frequent use of aspirin, ibuprofen & other anti-inflammatory drugs.
H2 blockers reduce the production of stomachacid, which may reduce
irritation to the stomachlining & help an ulcer heal. H2 blockers are
sometimes used in combinationwith antibiotics to treat H. pylori infections.

9. ☆ Dyspepsia
Dyspepsia, also known as indigestion, is a term that describes discomfort or
pain in the upper abdomen.
Its symptoms include heartburn, bloating, belching, discomfort, nausea,
vomitting, soar or upset stomach, abdominal pain, flatulence.
Causes -
1. Overeating,consuming caffeine, alcohol, greasy or spicy foods.
2. Diseases like ulcer, GERD, irritable bowel syndrome , pancreatitis etc
3. Certain medications like Aspirin, ibuprofen, pain killer, estrogen etc

10. ☆ Metabolic alkalosis
Metabolic alkalosis is a condition of reduce pH loss, that occurs when the
blood becomes overly alkaline
Causes -
1. Too many alkali-producing HCO3- ions
2. Too few acid-producing H+ ions
3. Gastrointestinal or renal acid loss
4. Vomitting, dehydration, Diuretics, Cushing syndrome.
5. Antacid use won’t normally lead to metabolic alkalosis. But if the
antacids are more water soluble, they may be able to produce systemic
alkalosis due to that of absorbable ions disturbing acid-base balance of
body fluids.

11. ☆ Antacids
Antacids are the medicine that help to combat excess acid in stomach
by neutralizing it.
Antacids contain ingredients like Al, Ca, Mg, or sodium bicarbonate
which act as bases (alkalis). These bases having pH above 7.0
chemically react with acid & counteract their effect.
▪ Uses of Antacids
1. They bring down the percentage of acidity in our stomach by
neutralizing excess acid.
2. They prevent from heart burn, upset or sour stomach. In addition,
prevent inflammation, relieving pain & discomfrt,
3. They minimize the symptoms of ulcers by preventing the stomach
acid from attacking the stomach lining, thus allowing it to heal.

12. ▪ Mechanism of Antacid
• Antacids contain ingredients like Al, Ca, Mg, or sodium bicarbonate which act as
bases (alkalis). These bases having pH above 7.0 chemically react with acid &
counteract their effect.
• Antacid perform neutralisation reaction, i.e. they react with HCl in stomach to
produce salt & water a hence make its pH more neutral as well as neutralize the
excess acid. This neutralisation makes the stomach contents less corrosive. This
can help to relieve the pain associated with ulcers & the burning sensation in acid
reflux.. Although they can't prevent the production of gastric acid.
• Some antacids reaction -
Al(OH)3 + 3HCl AlCl3 + 3H2O
Mg(OH)2 + 2HCl MgCl2 + 2H2O
MgO + 2HCl MgCl2 + H2O
NaHCO3 + HCl NaCl + H2O + CO2
CaCO3 + 2HCl CaCl2 + H2O + CO2

13. They promote the gastric mucosal defence mechanisms by secreting -
• Mucus : protective barrier against HCl.
• Bicarbonate : helps buffer acidic properties of HCl.
• Prostaglandins : prevent activation of proton

14. 1. Systemic antacids
• They are the antacids which are soluble & readily absorbed from the
intestine into the system circulation.
• Examples include - NaHCO3, Na3C6H5O7(Sodiumcitrate)
• They have quick onset but brief duration of action
• They may cause systemic alkalosis & disturbed the acid base balance
2. Non-systemic antacids
• They are the antacids which are insoluble & poorly absorbed from the
intestine into the system circulation due to formation of insoluble
compound.
• Examples include - CaCO3, Al(OH)2, Mg(OH)2
• They have slow onset but longer duration of action
• The don't disturb the acid base balance & not elevate the urinary pH.

15. Action of NaHCO3
NaHCO3 is a systemic antacid which is soluble & readily absorbed from the
intestine into the system circulation. It has quick onset but brief duration of
action.
NaHCO3 performs neutralization reaction, i.e. it reacts with HCl in stomach to
produce salt & water, hence make its pH more neutral as well as neutralize the
excess acid. This neutralization makes the stomach contents less corrosive. This
can help to relieve the pain associated with ulcers & the burning sensation in
acid reflux. Although they can't prevent the production of gastric acid.
NaHCO3 + HCl NaCl + H2O + CO2
Neutralization of HCl results in the formation of NaCl, carbon dioxide & water.
Approximately 90% of NaCl is converted to insoluble Na salts (e.g. Na
carbonate, Na phosphate) & rapidly excreted as urine.
Absorption of NaCl may increase Na load & can raise the pH of blood & urine.
Formation of CO2 results in flatulence & belching that can be dangerous if ulcer
is near perforation. The CO2 can also cause rebound acidity.

16. ▪ Antacid combination
Since no single antacid meets all the criteria for an ideal antacid, a
combinationof two or more antacids is frequently used. In this case they
complement each other. These may be superior to any single agent on the
following accounts.
1) Mg & Al containingpreparation togetherused to relieve heartburn, acid
indigestion& upset stomach; where Mg salts has fast onset but short
duration of action & Al salts has slow onset but long duration of action.
Mg salts act as a laxative whereas Al salts can cause constipation.
(ii) Mg & Ca containingpreparation where one is laxative & the later one is
constipative in nature

17. ▪ Side effects of antacids
1. Al Compounds may cause constipation. Al has been linked with
Alzeimer's disease, so its intake should be limited.
2. Mg Compounds may cause diarrhea & laxative effect.
3. Ca compounds containingmay also increase calcium output in the
urine, which might be associatedwith kidney stones.
4. Na compounds may increase intake of sodium & cause Natremia.This
may be deleterious for arterial hypertension,heart failure & many
renal diseases.
5. Carbonates may generate CO2 leading to bloating& flatulence.
Formation of CO2 can also cause rebound acidity.

18. ☆ Proton pump inhibitor
• PPIs are the drugs which reduce gastric acid secretion by blocking the action of
proton pump in stomach.
• Examples : Omeprazole, Esomeprazole, Lansoprazole, Pantaprazole, Rabeprazole.
• PPIs are the most widely used for peptic ulcer, GERD & related disorders because
of their efficacy &safety.
▪ MOA :
• PPI s are prodrugs. They are readily absorbed from the body. In the
parietal cells of stomach lining, they undergo a molecular rearrangement
to Sulfenamide cation(active metabolite) in presence of HCl.
• This cation makes a covalent disulfide bond with -SH group of
H+/K+ATPase which irreversibly block the action of H+/K+ ATPase enzyme
system (the gastric proton pump) of the gastric parietal cells. The H+/K+-
ATPases are ion pumps that use the energy of ATP to transport protons
(H+) in exchange for K+ions.
• Hence, this inhibition of the activity of parietal cells leads to prevention of
HCl in the stomach.

19. ☆ H2 blockers
• H2 blockers are the drugs which reduce gastric acid secretion by blocking the
action of H2 receptors
• Examples : Ranitidine, Cimetidine, Famotidine, Nizatidine, Raxotidine.
• They are usually used for dyspepsia, gastritis, GERD etc. They are less potent
than PPIs but good for short time use.
▪ MOA :
• Histamine is an autocoids that act as a local hormone, secreted from the the
enterochromaffin-like cells (ECL cells) of the lining of stomach. It stimulates
the secretion of gastric acid by binding with the Histamine H2 receptor in the
parietal cells.
• When H2 blocker is administrated into body, it travels to specific receptors
on the surface of the stomach cells that release acids. The active ingredients
reversibly bind to histamine H2 receptors in the stomach & prevent the H2
receptor from responding to histamine. This as well prevent histamine from
binding with its receptor on the gastric lining. This effect therefore depress
the amount of acid produced by the stomach.

20. ☆ Differences among them
Principle Antacids H2 blockers PPIs
Onset of action <10 min <1h 2-3d
Duration of action 30-60 min 9-12h 1-2d
Site of action In stomach lumen Inside parietal cell Inside parietal cell
End result of action Neutralize stomach
acid
Suppress gastric acid
secretion
Suppress gastric acid
secretion
Moa Neutralization of
gastric acid
Block the histamine
H2 receptor
Bloke the proton
pump system
Efficacy lowest >H2 blockers< Greatest
Side effects Headache, constipation,
nausea, diarrhea,
osteoporosis, pH
imbalance, kidney stone
Headache,constipation,
Diarrhea, rash, fatigue,
insomnia, muscle pain
Headache,constipation,
gas, abdominal pain.
fever, rash, pancreatitis
Examples Al(OH)2, Mg(OH)2 Omeprazole Renitidine

21. ☆ PPIs vs H2 blockers
• PPIs & H2 blockers both are used to reduce the secretion of gastric acid in
stomach. But they act in different mechanism & PPIs are more effective
than H2 blockers.
• Histamine, one of the first stimuli for acid production. H2 blockers act by
reversibly bind to the histamine H2 receptors in the stomach & prevent
the parietal cells in the stomachlining from responding to histamine
stimuli. Although there are other stimuli like Gastrin & Acetycholine which
trigger the proton pump of parietal cell to secrete proton (H+). So that
some acid is still being produced in stomachconstantly.
• On the other hand, PPIs block the final step in the pathway of acid
secretion in the stomach. PPIs act by iirreversibly blocking the action of
proton pump of the gastric parietal cells. This inhibits the activity of
parietal cells leads to prevention of acid in the stomach.

22. ☆ Anticholinergics
• Anticholinergics are the drugs which reduce the gastric acid secretion by
blocking the action of Muscarinic M3 receptor.
• Example : Pirenzipine, Telenzipine
• They are used to treat various health conditions e.g. Gastrointestinal
disorders, motion sickness, COPD, ashtma etc.
• Acetylcholine is a neurotransmitter, secreted from the cholinergic nerve
fiber of brain. It stimulates the gastric acid secretion by binding with the
M3 receptors in the gastric lining.
• When Anticholinergics is administrated into body, it travels to the the
M3 receptor on the surface of stomach linings that release acid.
• The active ingredients reversibly bind to M3 receptors & prevent the M3
receptor from responding to Acetycholine. This as well prevent
acetylcholine from binding to its receptors on the gastric lining. This
effect therefore depress the amount of acid produced by the stomach.

23. ☆ Mucosal Protective Drugs
• Mucosalprotective drugs are the drugs that protect the mucosal lining of
the stomach from acidic gastric juices.
• Examples : Sucralfate, Bismuth Subcitrate
• When these drugs are administrated into the body they react with the
stomach acid to form a cross linked viscous polymer.
(Sucralfate is Al salt of sulfated sucrose. It dissociates in the acidic env of stomach to
its anionic form, which react with the..)
• The polymer binds to protein molecules in stomach& form a protective
coating layer on the mucosallining particularly in ulcerated areas. The
coating restricts further acidic damage in stomach from gastric juice.
• Mucosalprotective drugs also sstimulates the mucosal prostaglandin &
bicarbonatesecretion. This helps ulcers heal more quickly.

24. ☆ Anti H. Pylori Drugs
• Helicobacter is a gram negative bacteria which attaches to gastric
epithelium. It interacts with the gastric epithelial cells, leads to
inflammation, damage & subsequently cause gastritis, dyspepsia, peptic
ulcer etc.
• Anti H. Pylori drugs are the drugs which produce large amounts of Urease
which hydrolyse urea into NH3. The NH3 then react with the H2O in the
parietal cell & form NH4OH, which neutralize gastric acid & create a
neutral protective cloud over the bacteria.
NH2CONH2 H2O 3NH3 + CO2
NH3 + H2O NH4OH ; NH4OH + HCl NH4Cl + H2O
• Examples : Amoxicillin, Clarithromycin, Metronidazole etc.
• Since no single agent is affective in eradicating the bacteria & besides H.
pylori becomes less virulent in absence of acid ; a combinationregimen is
preferred along with them using PPI or H2 blockers. For instance,
Dual therapy(7-10d) : Omeprazole(40mg OD) + Amoxicillin (1000 mg BD)