Drugs acting on GIT- Acidifiers

Gastrointestinal agents

v  The digestive system is the gastrointestinal tract which is the group of organs.

v The main portions of GIT include stomach, small intestine, large intestine and rectum with the exit anus.

v Stomach- Digestion of protein in acidic medium take place in pepsin enzyme

v Small intestine- Digestion of protein, carbohydrates and lipids in alkaline medium in presence of enzymes and bile salts

The above functions go wrong there occur diseases or undesirable conditions.

v Inadequate secretion of acid take place in the stomach causes Achlorhydria

v Excess secretion of acid take place in the stomach causes hyperchlorhydria (hyperacidity), ulcers

v Inadequate absorption of fluids and minerals from large intestine causing diarrhea

v Insufficient peristaltic movement of large intestine causing constipation

v Inadequate secretion of saliva, making the food to swallow with difficulty.

It is possible to correct the above conditions by administration of suitable drugs.

Classification of gastrointestinal agents

v Acidifiers - Increase the level of gastric acid in the stomach

v Antacids- Neutralize excess stomach acid

v Cathartics/Purgatives/Laxatives-                      To bring about defecation/ mild action of cathartics/ mild action purgatives

v Adsorbents –    Ability to adsorb gases, toxins and bacteria

Acidifiers

v  These substances increase the level of gastric acid in the stomach when ingested, thus decreasing the stomach pH.

v These are drugs which enhance the gastric secretion and improve digestion in stomach. These agents are administered for

1. Hypochlorhydria 
2. Achlorhydria

Mainly there are four types of acidifiers

1. Gastric acidifiers- These are the drugs which are used to restore temporarily the acidity of the stomach in patients suffering from Achlorhydria or Hypochlorhydria.
2. Urinary acidifiers - These are the drugs which are used to render acidic urine to enable treatment of some types of urinary tract disorder.
3. Systemic acidifier -These are the drugs which are able to neutralize the alkaline body fluids, particularly blood, in patients who are suffering from systemic alkalosis.
4.  Acids - These are used as pharmaceutical aids in the preparation, laboratory quality control etc., Eg. HCl and NH₄Cl

1. Dilute Hydrochloric acid (dil. HCl)

Preparation:

It is prepared from conc. HCl by diluting 274g of the acid with 726g of purified water.

Uses:

Ø  Acidifier

Ø  To treat achlorhydria

Ø  Uses as a reagent in the laboratory

Dose - 0.6 to 8ml

2. Ammonium Chloride (NH₄Cl)

Preparation:

1. It is prepared commercially by combining ammonia (NH₃) with either hydrogen chloride gas or hydrochloric acid

                        NH₃ + HCl → NH₄Cl

2. It is prepared by boiling ammonium sulphate solution with calculated amount of sodium chloride.

                             (NH₄)₂SO4  +  2NaCl ------à 2NH₄Cl  + Na₂SO₄

At boiling point the less soluble sodium sulphate is crystallised and removed. The mother liquor is evaporated to get ammonium chloride.

Uses:

It exhibit the following pharmacological actions. These actions are dose dependent

Ø  Expectorant

Ø  Diuretic

Ø  Systemic acidifier

Ø  Maintaining acid base equilibrium of body fluids

Storage condition:

Since it is hygroscopic, it is stored in a well closed container

Assay :

Estimated by two methods

Formal Method                       2. Modified Volhards method

1. Formal Method

Principle :

It is assayed by acid base titration (alkalimetry). In this assay ammonium chloride reacts with formaldehyde solution liberating equal amount of hydrochloric acid after the formation of hexamine. The liberated hydrochloric acid is titrated against standard sodium hydroxide solution using phenolphthalein as an indicator.

4NH₄Cl  +  6 HCHO   -----à  (CH₂)₆N₄   +  4HCl  + 6H₂O

Liberated HCl  +  NaOH  ---à NaCl  + H₂O

HCHO must be previously neutralized, otherwise the acidic impurity (formic acid) present in it will consume some amount of NaOH leading to over titration.

Procedure

v  Weigh accurately about 0.1g of ammonium chloride and transfer into a conical flask. 

v  Dissolve in 20ml of water; add a mixture of 5ml of formaldehyde previously neutralized to phenolphthalein.

v Allow to stand for 10minutes and then titrate with 0.1N. NaOH using phenolphthalein as indicator until a pale pink colour appears.

v Each ml of 0.1N sodium hydroxide is equivalent to 0.00534g of ammonium chloride.

2. Modified Volhards method

v A solution of the substance acidified with nitric acid is shaken with a measured volume of silver nitrate solution

v Nitrobenzene is added to coagulate the precipitate of silver chloride.

v So that it will not interfere with the titration later of excess of silver nitrate which is determined by titration with ammonium thiocyanate using ferric ammonium sulphate as indicator.

AgNO3  +  NH4Cl   ------------à AgCl  +  NH₄NO₃

AgNO₃  +  NH₄SCN  ---à  AgSCN    +  NH₄NO₃

FeNH₄(SO₄)₂   + 3NH₄SCN   ---à 2 (NH₄) ₂SO₄  +  Fe(SCN)₃

Procedure:

v Dry about 0.2 g of the sample over silica gel for 4 h, weigh accurately, and dissolve it in about 40 ml of water in a glass-stoppered flask.

v Add 3 ml of nitric acid, 5 ml of nitrobenzene, 50ml of 0.1N silver nitrate, shake vigorously, then add 2 ml of ferric ammonium sulfate.

v  Titrate the excess silver nitrate with 0.1 N ammonium thiocyanate.

Each ml of 0.1 N silver nitrate is equivalent to 5.349 mg of NH₄Cl.