Gastrointestinal agents

1. UNIT-III
a) Gastrointestinal agents
Prepared by
Mr. Girish Kashid
Asst. Prof.
Department : Pharmaceutical Chemistry

2. The food we eat contains a variety of nutrients, which are used for
building new body tissues and repairing damaged tissues. Food is also
vital to life because it is our only source of chemical energy.
However, most of the food we eat consists of molecules that are too
large to be used by body cells. Therefore, foods must be broken down into
molecules that are small enough to enter body cells, a process known as
digestion (dis- apart; -gerere to carry).
The organs involved in the breakdown of food—collectively called
the digestive system
Introduction

3. Two groups of organs compose the digestive system
1) Gastrointestinal (GI) tract
2) Accessory digestive organs
1) The gastrointestinal (GI) tract, or alimentary canal
(alimentary nourishment), include the mouth, most of the pharynx,
esophagus, stomach, small intestine, and large intestine.
2) The Accessory digestive organs include the teeth, tongue,
salivary glands, liver, gallbladder, and pancreas.

4. Organs of the
digestive system

5. The digestive system performs six basic processes:
1. Ingestion:
This process involves taking foods and liquids into the mouth
(eating).
2. Secretion:
Each day, cells within the walls of the GI tract and accessory digestive
organs secrete a total of about 7 liters of water, acid, buffers, and enzymes
into the lumen (interior space) of the tract.
3. Mixing and propulsion:
Alternating contractions and relaxations of smooth muscle in the
walls of the GI tract mix food and secretions and propel them toward the
anus. This capability of the GI tract to mix and move material along its
length is called motility.

6. 4. Digestion:
Mechanical and chemical processes break down ingested food into
small molecules.
In mechanical digestion the teeth cut and grind food before it is
swallowed, and then smooth muscles of the stomach and small intestine
churn the food.
As a result, food molecules become dissolved and thoroughly mixed
with digestive enzymes.
In chemical digestion the large carbohydrate, lipid, protein, and
nucleic acid molecules in food are split into smaller molecules by hydrolysis

7. 5. Absorption:
The entrance of ingested and secreted fluids, ions, and the
products of digestion into the epithelial cells lining the lumen of the GI
tract is called absorption
6. Defecation:
Wastes, indigestible substances, bacteria, cells sloughed from
the lining of the GI tract, and digested materials that were not absorbed in
their journey through the digestive tract leave the body through the anus
in a process called defecation

8. List Of GI disorders
In event of impaired functions, the gastrointestinal (GI) disturbances
follows eg:
• Absence or insufficient secretion of hydrochloric acid in stomach -leading to
achlorhydria or hypochlorhydria.
• Excessive secretion of hydrochloric acid in stomach leading to hyperacidity,
which causes ulcers inflammation Acute pain.

9. • Accumulation of toxins, gases, toxic substances etc; or
insufficient absorption of fluids or electrolytes in the intestine
stimulates intestine motility leading to diarrhea.
• Insufficient intestine motility leads to peristalsis leading to
constipation.

10. 1. Acidifying Agents – Drugs which increase the gastric acidity
are known as Acidifying Agents
Eg:- Dil HCl
2.Antacids – Drugs which neutralizes the excess of HCL
secreted in the stomach.
Eg:- Sodium Bicarbonate, Alumnium hydroxide gel,
Calcium carbonate etc.
3. Protective & Adsorbents :- used in treatment of dirrhoae
Eg:- Bismuth sub carbonate, Kaolin
4. Saline Cathartics:- are used to relieve constipation Sodium
Potassium Tartrate, Magnesium Sulphate etc.
Classifications

11. Hypochlorhydria
Whenever inadequate secretion of acid takes place in the stomach,
this causes achlorhydria or hypochlorhydria. Acidifying agents/acidifiers are
used in treatment of Hypochlorhydria.
Acidifying agents/acidifiers:
The drugs or agents which are used to increase metabolic acidosis
and gastric hydrochloric acid. They are also known as acidifying agents or
acidifiers.
e.g. 1. Ammonium Chloride
2. Dil HCl

12. 1. Acidifying reagents/acidifiers:
These are drugs or agents which are able to increase acidity in GIT.
Some of the drugs are used to increase metabolic acidosis whereas some of
these are used to increase the gastric hydrochloric acid. They are also known
as acidifying reagents or acidifiers.
❖ Gastric acidifiers:
These are drugs which are used to restore temporarily the acidity of
stomach in patients suffering from achlorhydria or hypochlorhydria.
❖ Urinary acidifiers:
These are the drugs which are used to render acidic urine to enable
treatment of some type of urinary tract disorders.

13. ❖ Systemic acidifiers:
These are the drugs which are able to neutralize the alkaline body
fluids, particularly blood, in patients who are suffering from systemic
alkalosis.
❖ Acids:
Acids are used as pharmaceutical aids in the preparation,
laboratory quality control etc.

14. Properties:
❖ White, fine, coarse crystalline powder.
❖ Odourless
❖ Cool saline taste.
❖ A solution of 0.8% of ammonium chloride is isotonic with serum.
❖ It is freely soluble in water and in glycerin it is sparingly soluble in
alcohol.
NH4Cl+ 2H2O ----------------------------→ NH4OH + H3O+ + Cl-
Ammonium Chloride (NH4Cl)
Molecular Weight: 53.491 g/mol

15. Preparation:
It is prepared by neutralizing hydrochloride acid with ammonia,
and evaporating the solution to dryness. The product is purified by bye
re-crystallization or by sublimation.
Reaction:
Assay:
A weighed quantity is dissolved In water and formaldehyde solution
is added. It is titrated with 0.1N NaOH solution using phenolphthalein as
indicator
Each ml of 0.1N NaOH= 0.005349 gm of NH4Cl

16. Uses of Ammonium Chloride:
•It is used in fertilizers as a nitrogen source.
•It is used in medicine (especially in cough medicine) as an
expectorant.
•It is used in glue which helps to bond plywood.
•It is used as an acidifier.
•It is used in cooling baths to create low temperatures.
•They are used as buffer solutions along with ammonia.

17. Dilute Hydrochloric acid:
Formula : HCl Mol. Wt: 36.46
Hydrochloric acid is commonly known as spirit of salt
Properties:
1. It is a colourless liquid , strongly acidic.
2. It is miscible with water, alcohol having a specific gravity of 1.18
3. It is a strong acid and attacks metals, forming their hydrochlorides with the
evolution of hydrogen gas.
4. Even in high diluted form, it is very strongly acidic to litmus.

18. Uses:
1. It is mainly used as a pharmaceutical aid or as an acidifying agent.
2. Used as gastric acidifier when levels of hydrochloric acid in gastric
juice are low.
3. Externally used as a solvent, catalyst in basic pharmaceutical and as
acidifier.

19. 2. ANTACIDS:
These are drugs which are usually alkaline substances and are used to
neutralize the excess acid in the stomach of patients suffering from
hyperacidity. (a condition in which the level of acid in the gastric juices is
excessive, causing discomfort.)
Strong alkaline bases will damage the mucosal layer.
The action of antacids should be gradual without evoking rebound
acidity. Also antacids should no have any side effects.
Antacids give symptomatic relief from pain by neutralizing excess of
hydrochloric acid.
So they find use in treatment of ulcers by reducing pain.

20. 1) Systemic (absorbable) antacids:
These are soluble, readily absorbable and capable of producing systemic electrolytic
alteration and alkalosis. eg. Sodium bicarbonate
2) Non-Systemic (non-absorbable) antacids:
These are not absorbed to a significant extent and thus do not alter an appreciable systemic
effect. This group is further divided into following:
a) Aluminium containing antacids: e.g Aluminium hydroxide, Aluminium phosphate, Basic
aluminium carbonate, Dihydroxyaluminium aminoacetate
b) Calcium containing antacids: e.g Calcium carbonate, Tri basic calcium phosphate
c) Magnesium containing antacids: e.g Magnesium carbonate, magnesium hydroxide,
magnesium citrate, magnesium oxide, magnesium peroxide, magnesium trisilicate, magnesium
phosphate.
d) Combination antacid preparations:
e.g. Aluminium hydroxide gel and magnesium hydroxide,
Aluminium hydroxide gel and magnesium trisilicate
Semithicone containing antacids
Calcium carbonate containing antacids
Classifications

21. Ideal requirements of Antacids:
❖ It should be insoluble in water and has fine particle form.
❖ It should not be absorbable or cause systemic alkalosis.
❖ It should be able to exert its effect gradually and over a long period of
time.
❖ It should not be a laxative or cause constipation.
❖ It should not cause any side effect.
❖ It should be stable and readily available.
❖ The reaction between antacid and gastric hydrochloric acid should not
produce large volume of gas.
❖ The antacid should buffer in the pH range 4-6.
❖ Antacid should probably inhibit pepsin, the proteolytic enzyme.

22. Antacid preparations are administered as oral
suspension, mixtures, tablets, chewable tablets, capsules, and
oral products.

23. 1. SODIUM BICARBONATE
Chemical formula :- NaHCO3
Mol wt :-84.01
Common name :-Baking Soda, Mitha Soda
Synonym :-Sodium Hydrogen Carbonate
Preparation:-
A) Industrial Scale:-
prepared by Solvay process.
❖ Brine Sol (NaCl) is saturated with ammonia to remove
impurities.
❖ Sol is filtered & passed through carbonating tower & allow to
cool to enhance ppt.
❖ NaHCO3 is less soluble in water below 15°C the ppt is filtered
& Dried.

24. B) LAB SCALE :-
Prepared by passing through CO2 gas through solution of NaOH.
Solution is concentrated to obtain the product.
Reaction :
Reaction :

25. Properties:-
Colour:-White
Nature:-Amorphus
Taste:-Saline
Solubility:-Soluble in water insoluble in alcohol.
Incompatibility:- It inhibits the absorption of tetracycline from the
gastrointestinal tract.
Storage: it should be stored in well-closed containers.
Assay : An aqueous solution of sodium bicarbonate is treated with 1N HCl
using methyl orange as an indicator.

26. USES:-
1) Sodium bicarbonate was used as an antacid to reduce excessive acidity of
gastric juice. sharp Increase in gastric pH 7.
Neutralizes HCL but results in the production of CO2 causing belching (ढेकर)
and flatulence (पेट फ
ू लना), is not desirable.
2) Treatment of systemic acidosis.
3) It is used as electrolyte replenisher.
4) 5% solution of sodium bicarbonate is used as ear drops to an remove ear
wax.
5) 3.5% solution warm water is used as eye lotion.
7) It is also an ingredient in many effervescent antacid preparation.
NOTE:-Cardio vascular patients or those on sodium restricted diet .
advised to avoid this antacid.
Usual dose :-300 mg to 2 g four times a day.

27. Aluminium hydroxide is official in IP in two forms :
a) Aluminium Hydroxide Gel
b) Dried Aluminium Hydroxide Gel
2. Aluminium hydroxide gel Al(OH)3
It is an aqueous white viscous suspension of hydrated aluminum oxide
having varying amounts of basic aluminum carbonate and bcarbonate.
The preparation may sometimes have methyl oil, peppermint oil,
glycerine, sucrose or saccharin as flavoring and sweetening agents and
upto 0.05% sodium benzoate as preservative.
2. Aluminium hydroxide gel Al(OH)3

28. It is a white viscous suspension. Aluminum hydroxide gel gives astringent
aluminum chloride when it reacts with gastric hydrochloric acid. This
results in nausea, vomiting and constipation.
Al(OH)3 + 3HCl ‐‐‐‐‐‐‐‐‐‐‐‐ > AlCl3 + 3H2O
Synonym:- Aluminium Hydroxide/Hydrate Powder
Colour:-White
Nature:-Amorphus
Taste:- Tasteless
Solubility:-Soluble in mineral acids insoluble in water alcohol
Its pH is in the range 5.5-8.
Astringent
(तुरट) aluminium
chloride

29. Uses:
❖ They are non-absorbable and produce practically no systemic
effects. The aluminum hydroxide gels buffer in the pH 3-5 region by
virtue of their amphoteric character.
❖ Reaction with hydrochloric acid gives the water soluble astringent
salt aluminum chloride. Hence, it may cause constipation and nausea.
❖ It eventually forms the resoluble aluminium phosphate in the
intestines leading to increased faecal phosphate excretion.

30. Dried Aluminium Hydroxide Gel
Synonym: Aluminium hydroxide powder
Properties:
❖ It is a white amorphous powder
❖ Colourless and tasteless
❖ Insoluble in water
❖ Uses:
1. Used as an antacid.
2. Dried aluminum hydroxide gel is used externally as a desiccant.
3. It is a constituent of some foot powders.
4. Used in the treatment of diarrhea as protective.

31. 3. Magnesium containing antacids
Magnesium carbonate (Heavy and Light) (MgCO3)
Magnesium hydroxide (Milk of Magnesia) (Mg(OH)2
Magnesium oxide (MgO)
Magnesium trisilicate,
Magnesium phosphate.

32. a) Magnesium Carbonate, I.P. : (Magnesium carbonate hydroxide)
Approximate formula 3MgCO3.Mg(OH)2.4H20
Magnesium carbonate is recognised in I.P. in two forms which
differ in density. Both forms are chemically hydrated basic
magnesium carbonates and contain the equivalent of 40-45per cent
of MgO.
i) Heavy Magnesium Carbonate, I.P.,: It is a white odourless
powder with a density of 0.5 gm/ml.
ii) Light Magnesium Carbonate,: I.P.,: It is a very light, white
powder with a density of 0.12 gm/ml.

33. Properties:
➢ Magnesium carbonate is insoluble in water and alcohol.
➢ It dissolves in dilute acids with effervescence.
➢ It is a hydrated mixture of magnesium carbonate and magnesium
hydroxide.
Uses:
➢ The antacid properties of magnesium carbonate are due to reaction of
carbonate and hydroxide ions with gastric hydrochloride acid.
➢ The magnesium cation causes a laxative effect.
➢ Hence the magnesium containing antacids are often given in
combination with aluminium and calcium antacids, which tend to
cause constipation.

34. b) Magnesium Trisilicate, I.P.:
It is hydrated magnesium silicate corresponding approximately
to formula 2Mg0.3Si02nH2O. It is a compound of magnesium oxide
and silicon dioxide with varying proportions of water of
crystallization.
It contains not less 29 per cent and not more than 32 per cent
of Mgo and not less than 65 per cent and not more than 68.5 per
cent of SiO2 calculated with reference to the substance ignited at
900°C.

35. Properties:
✓ It is an odorless, tasteless slightly hygroscopic, white powder free from
gritty particles.
✓ IP. specifies that it loses 20-30 per cent of its weight on ignition.
✓ It is assayed in terms of silicon dioxide and magnesium oxide.
✓ Magnesium trisilicate is practically insoluble in water and Alcohol

36. Uses:
❖ It interacts slowly with dilute hydrochloric acid forming sodium
chloride and colloidal silica.
❖ In the stomach, a gelatinous mass of colloidal silicon dioxide and silicic
acid is formed.
❖ The compound may also be considered as a protective and adsorbent.
❖ The colloidal silicates may protect the ulcer from further acid and peptic
attack, and possibly adsorb pepsin.
❖ Presently, magnesium trisilicate is used in combination products to
overcome the constipating effect of calcium-or aluminium containing
antacids.

37. c)Magnesium Oxide, IP.: (Magnesia)
MgO, Molecular weight 40.3
It is recognised in two forms.
i) Light Magnesium Oxide, I.P. : It is a very bulky white powder with a
density of 0.1 gm/ml.
ii) Heavy Magnesium Oxide, IP, : It is a relatively dense white powder
with a density of 0.5 gm/ml
Both forms contain not less 98.0 per cent of MgO, calculated with reference
to the substance ignited at 900°C.
Light Magnesium Oxide Heavy Magnesium Oxide

38. Properties:
➢ Magnesium oxide is a fine, white, odourless powder with slightly
alkaline taste.
➢ It is practically insoluble in water and alcohol but dissolves in dilute
acids, with formation of magnesium hydroxide.
➢ Hence the chemistry and pharmacology of magnesium oxide and
magnesium hydroxide are similar.
Uses:
➢ It is a potent antacid and mild laxative.
➢ When prescribed in mixtures, light magnesium
oxide is used bot for powders and tablets, the
heavy form is preferred.

39. d) Magnesium Hydroxide, I.P.:
It contains 95.0 to 100.5 percent of Mg(OH)2
Properties:
✓ It is a bulky, white, odourless powder.
✓ It is practically insoluble in water and in ethanol.
✓ It dissolves in dilute acids.
Uses: Antacid, osmotic laxative.

40. 4. Calcium Carbonate, I.P.: (Precipitated chalk)
CaCO3, Molecular weight=100.09
Calcium carbonate is precipitated calcium carbonate. It
contains not less than 98 per cent and not more than the 100.5
percent of CaCO3 calculated with reference to the dried
substance.
Properties:
❖ Calcium carbonate is a fine, white odourless and tasteless
microcrystalline powder.
❖ It is practically insoluble in water and in alcohol.
❖ It dissolves with effervescence in dilute hydrochloric acid and other
acids.

41. Uses:
➢ The major difference between the activities of calcium carbonate and
aluminium antacids is that the action of the former depends on its
basic properties while that of the latter depends on its amphoteric
nature.
➢ Calcium carbonate is rapidly acting and largely non-systemic.
➢ Calcium carbonate causes constipation and is therefore given in
combination with a magnesium antacid.
➢ Other side effects observed are hypercalcaemia and alkalosis.

42. Combination Preparations of Antacids
No single antacid may be considered ideal.
Many of the marketed products contain two antacids to approach the
ideal behaviour.
The combinations commonly attempt to balance the constipative
effect of calcium and aluminium with the laxative effect of magnesium.
Some products combine one antacid with rapid onset of action and another
with long duration of action.

43. 1. Aluminium Hydroxide gel-magnesium hydroxide
2. Magaldrate (Hydrated Magnesium aluminate, monalium hydrate)
3. Aluminium hydroxide gel-magnesium trisilicate
4. Combinations containing calcium carbonate
5. Combinations containing alginic acid
6. Products containing simethicone
The important combinations used are -

44. 1. Aluminium Hydroxide gel-magnesium hydroxide:
The combination tends to remove the constipative and laxative effects of
the individual antacids. In suspension, 2-4 per cent of each agent is used.

45. 2. Magaldrate: (Hydrated Magnesium aluminate, monalium hydrate)
Approximate formula: Al12H14Mg4O142H20, Molecular weight: 425.3
Magaldrate is a chemical combination of aluminium hydroxide and
magnesium hydroxide.
It is superior to the simple admixture. Magaldrate contains the
equivalent of 28-39 per cent magnesium oxide and 17-25 per cent of
aluminium oxide.
It occurs as a white, odourless, crystalline powder which is insoluble in
water and alcohol but soluble in dilute mineral acids.

46. 3. Aluminium hydroxide gel-magnesium trisilicate:
This combination gives the additional benefit of the protective effect
of magnesium trisilicate.
4. Combinations containing calcium carbonate:
❖ Calcium carbonate is combined with aluminium hydroxide gel to yield
products with rapid onset and prolonged action.
❖ It is also combined with the magnesium antacid to balance the
constipative effect of calcium with the laxative effect of magnesium.

47. 5. Combinations containing alginic acid:
Preparations containing the hydrophilic colloid alginic acid along with sodium
bicarbonate, aluminium hydroxide gel and magnesium trisilicate have been
marketed.
These are useful to provide relief in reflux oesophagitis. While passing
to the stomach alginic acid reacts with sodium bicarbonate forming sodium
alginate and carbon dioxide. Alginic acid is precipitated which floats on the top
of the foam along with the antacids.
6. Products containing simethicone:
Simethicone is a defoaming agent. It is added to some antacids to give relief
from flatulence.