Gastrointestinal Agents

Gastrointestinal agents includes many classes of drugs that are used to treat gastrointestinal disorders

1. Sonali Gadge Asst. Professor, M.Pharm (QA ) P.R.Patil , institute of pharmacy, Talegaon (SP), Dist- Wardha Gastrointestinal Agents Presented by :

2. CONTENTS : Introduction Functions of Stomach and Small Intestine Diseases of GIT Detail classification Acidifying agents – Dil. HCl Antacids – Classification Ideal requirements Marketed antacid preparation Cathartics Antimicrobial Agents – Classification Mechanism of Action Characteristics Monograph of Iodine Monograph of Hydrogen Peroxide

3. Introduction The digestive system is the Gastrointestinal tract (GIT) which is a group of organs. It extends from Alimentary canal to the anus. The entrance to the system is the buccal cavity i.e. mouth. The main portions of GIT include- Stomach Small Intestine – i ) Duodenum ii) jejunum iii) ileum Large Intestine – i ) Caecum ii) Ascending colon iii) Transeverse colon iv) Descending colon Rectum with the exit anus

4. Stomach In stomach, digestion of proteins in acidic medium takes place with pepsin enzyme. Both HCl & enzyme are secreted in the stomach by specialised cells. Small intestine In small intestines, the following changes takes place – Digestion of proteins takes place in alkaline medium in presence of enzymes. Digestion of cabohydrates & lipids takes place in presence of enzymes & bile salts. Absorption of digested foods, vitamins & minerals takes place.

5. Disease of GIT Inadequate secretion of acid takes place in the stomach, causes Achlorhydria or Hypochlorhydria . When excess secretion of acid takes place in stomach, causes Hyperacidity or Hyperchlorhydria . There may occur accumulation of toxic substances or gases. There may occur inadequate absorption of fluids and minerals from large intestine, thereby causing diarrhoea . There may occur insufficient peristaltic movement of large intestine thereby causing constipation. There may occur inadequate secretion of saliva, thereby making the food to swallow with difficulty.

6. Detail Classification Acidifying Agents or Acidifiers Gastric acidifiers – eg . HCl Urinary acidifiers Systemic acidifiers Acids B. Antacids Systemic ( absorable ) antacids – eg . Sodium bicarbonate Non-systemic (non- absorable ) antacids a) Aluminium containing antacids eg .- Aluminium hydroxide , Aluminium phosphate b) Calcium containing antacids eg . – Calcium containing antacids, Tribasic calcium phosphate c) Magnesium containing antacids eg . – Magnesium carbonate, Magnesium hydroxide

7. d ) Combination antacid preparation – eg .- Aluminium hydroxide gel & Magnesium hydroxide Aluminium hydroxide gel & Magnesium trisilicate C. Protectives and Adsorbents Bismuth compounds- Bismuth subcarbonate , Bismuth subnitrate D. Cathartics 1. Stimulants - eg . Senna , rhubarb, cascara, podophyllum , castor oil, etc. 2. Bulk purgatives – eg . Methylcellulose, sodium carboxymethylcellulose , gum, isapgol , etc. 3. Lubricants - eg . Liquid paraffin, glycerin, etc. 4. Saline Cathartics – eg . Magnesium hydroxide, magnesium sulphate,etc

8. Acidifying agents/Acidifiers These are the inorganic chemical substances that either produce or increase acids. These chemicals increase the level of acid in the stomach when ingested, thereby decreasing the stomach PH. Gastric acidifiers : These are the drugs which are used to increase acidity of the stomach in patients suffering from achlorhydria or hypochlorhydria . Urinary acidifiers : These are the drugs which are used to remove acidic urine from the body or to maintain the PH of urine. Systemic acidifiers : These are the drugs which are able to neutralise alkaline body fluids, specially bloodor to maintain the Ph of all parts of body. Acid : These are used as pharmaceutical aids in preparation of medicaments.

9. Hydrochloric Acid Molecular formula : HCl Molecular wt. : 36.46 Synonyms : Spirit of salt, Muriatic acid Preparation : It can be prepared by the action conc. Sulphuric acid on Sodium Chloride and passing the liberated Hydrogen Chloride through water. NaCl +H2SO4 NaHSO4 + HCl Properties: It is nearly colourless clear and fuming liquid. It possesses pungent odour . It is soluble with water and alcohol. It is a strong acid and attacks metals, foaming the hydrochlorides with the evolution of gas. Chemical properties : It reacts with sodium metal which results in the formation of sodium chloride and liberates hydrogen gas. 2Na + 2 HCl 2NaCl + H2 2. It is oxidised by strong oxidising agents liberating chlorine gas. 2 KMnO4 + 16 HCl 2 MnCl2 + 2 KCl + 8 H2O + 5 Cl2

10. Storage : It is stored in well closed container of glass or other inert material at a temperature not exceeding 30 c. Uses : It is used as a pharmaceutical aid or as an acidifying agents. Used as gastric acidifiers when levels of hydrochloric acid in gastric juice are low. Externally used as a solvent, catalyst in bais pharmaceuticals and as acidifiers. Dose : 0.6- 8 m l

11. Antacids These are the drugs or preparations which neutralise excess HCl in the body. Antacids are usually alkaline substances & it is given to the patients suffering from Hyperchlorhydria (hyperacidity) It is known that the production of gastric hydrochloric acid is a continual process. It means that administration of antacids is also a continual process. Under the normal physiological conditions, hydrochloric acid is secreted by epithelial cells of gastric mucosa. The PH of stomach depends upon the intake of food. If antacids are water soluble, may produce systemic alkalosis because of absorable ions disturbing acid base balance of body fluids. Depending upon the location ulcers can be classified as oesophageal ulcer( affets oesophagus ), gastic ulcer(affects gastric mucosa), duodenal ulcer (affects duodenum)

12. Antacids are classified as follows : Systemic( absorable ) antacids : These are water soluble and cause metabolic alkalosis. Eg . – Sodium bicarbonate 2 ) Non- systemic (non- absorable ) antacids : These are not absorbed to a significant extent. This group is further divided into following : Aluminium containing antacids : eg .- Aluminium hydroxide (AlOH3), aluminium phosphate(AlPO4), dihydroxyaluminium aminoacetate , dihydroxyaluminium sodium carbonate, basic aluminium carbonate. Calcium containing anatcids : eg . – calcium carbonate, tribasic calcium phosphate. Magesium containing antacids : eg .- Magnesium carbonate, Magnesium citrate, ,magnesium hydroxide, magnesium oxide Combination antacid preparation : Aluminium hydroxide gel & magnesium hydroxide. Aluminium hydroxide gel & magnesium trisilicate .

13. Ideal requirements of Antacids : The antacid should be absorable or cause systemic alkalosis. The antacid should not be laxative or cause constipation. The antacid should exert it’s effect rapidly and over a long period of time. The antacid should probably inhibit pepsin. The antacid should have buffer in the PH range of 4-6. The reaction of the antacid with gastric hydrochloric acid should not cause a large evolution of the acid.

14. Table : Marketed Anatcid Preparation Brand Name Ingredients Gelusil Al(OH) 3 and Mg(OH) 2 with M.P.S. Digene Al(OH) 3 and Mg(OH) 2 with M.P.S. Siloxogene Al(OH) 3 and Mg(OH) 2 and Simethicone Almacarb Al(OH) 3 with liquorice Cogel Al(OH) 3 with MgCO 3 Solacid Al(OH) 3 , Mg(OH) 2 and magnesium trisilicate

15. Cathartics : These are the drugs which brings about defecation. They are beneficial in constipation and for expulsion of intestinal parasites. In normal habits, peristalsis causes defecation. The peristaltic waves are able to stimulate bowel and relieve it’s contents. The peristaltic motion normally takes place about 3-4 times a day. Constipation can also be due to many factors like weakness of intestine, intestinal spasm, injury or use of certain drugs & diets, etc. In constipation fecal material becomes dry & hard. Cathartics or purgatives generally act by four different mechanisms.

16. Cathartics or purgatives generally act by four different mechanisms. Stimulants Saline Cathartics Lubricants Bulk Purgatives Cathartics

17. Stimulants : These are the drugs or chemicals which act by local irritation on intestinal tract and bring about stimulation of peristaltic activity. As they are directly act on intestine & stimulate peristalsis, they are termed as stimulants. Eg .- Senna , Castor oil, rhubarb, etc. Bulk Purgatives : These are the agents which are able to increase bulk of intestinal contents. These are soluble or non- digestable type of materials. Eg .- Methylcellulose, sodium carboxymethylcellulose , gum, isapgol , etc. Lubricants : In constipation, contents of intestine become hard because of absorption of water by body, there results in difficulty in clearing bowels. Eg .- Liquid paraffin, glycerin, etc.

18. Saline Cathartics : These act by increasing the osmotic load of intestine by absorbing large quantity of water & thereby stimulate peristalsis. Poorly absorable cations like calcium, magnesium, & anions like phosphate, sulphate , tartrate are contributing to this effect. Saline cathartics are water soluble and they are taken with plenty of water. This is helpful in restricting excessive loss of body fluid & reduces nausea and vomitting . They may be administered by oral route in the form of suspension, tablet or in other suitable formulations. Eg .- magnesium hydroxide, Magnesium sulphate , etc. & tartrate salts of Na & K.

19. Protectives and Adsorbents Protectives and adsorbents are the chemically inert substances which are used in the treatment of diarrhoea . Diarrhoea is defined as the frequent passage of watery stools or liquid faeces . As a result of increased motility in the colon, the stool may contain blood, pus, mucus, or excess quantity of fats. It may be mild or chronic diarrhoea . Mild diarrhoea is due to bacterial infections with their toxins, side effects of some drugs, hypersensitivity, accidental or intestinal poisoning while chronic diarrhoea is due to the GIT disturbances, absorption and inflammation. Excess discharge of intestinal content leads to the loss of electrolyte which give rise to Dehydration or Electrolyte Imbalance. Inorganic compounds such as Bismuth Subcarbonate , Kaolin, Bentonite , etc. are insoluble salts which are used as protectives and adsorbents.

20. Antimicrobial Agents An antimicrobial (disinfectant & Antiseptic) is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi or protozoans . Antimicrobial agents either kill microbes ( microbiocidal ) or prevents the growth of microbes ( microbiostatic ).

21. Classification of Antimicrobial Agents Antiseptics Disinfectants Germicides Bacteriostatics Sanitizers

22. Antiseptics These are the substances that are able to kill or prevent the growth of microorganisms. It acts by inhibiting their activity or destroying them specially by applying to the living tissues like surface of skin, application of antiseptic dressings on wounds. The drugs like phenol, iodine, boric acid, cetrimide are the examples of antiseptics. Disinfectants These are the substances that are used to prevent growth or multiplication of microorganisms. It is used to apply on inaminate objects (non-living objects) Disinfectants are widely used for home & hospital sanitation. All disinfectant solutions undergo deterioration under storage & elevated temperature. Ex- cresol, phenol

23. Germicides : These are the substances which kills microorganisms. Specific terminology like “ Bactericide”(against bacteria), “ fungicide” (against fungi), “ virucide ”(against virus), etc. denotes exact action. Bacteriostatics : These are substances which inhibits the growth of bacteria. Thus, bacteriostatics drugs or agents do not kill but arrest the growth of bacteria. Sanitizers : Disinfectants that are used to maintain general public health standards, ae termed as Sanitizers. Sanitation is mainly concerned with cleaning or washing away the organic matter(saliva, mucous, etc.) Sanitation can be achieved only with surfaces & articles that are physically clean. High concentration of sanitizers also cause local cellular damage.

24. Mechanism of action The mechanism of action of antimicrobial agents may range from a mild astringent to powerful oxidative processes. Inorganic compounds are generally not used as antiinfectives for systemic infections i.e. they are not administered internally like antibiotics or sulphonamides . For topical applications(dermatological, oral, ear, opthalmic , etc.) they may be used with caution. Inorganic compounds exhibits antimicrobial action by involving either of the following three mechanisms i ) Oxidation ii) Halogenation iii) Protein binding or precipitation

25. Oxidation mechanism Examples of compounds acting by this mechanism are peroxides of peroxy acids, oxygen liberating compounds like potassium permagnate . They bring about oxidation of active functional groups present in proteins and enzymes vital to the growth and survival of microorganisms. This causes a change in the confirmation of the proteins & thereby alters it’s function. For ex- a free sulfhyhydryl group has been essential for functioning of a variety of proteins & enzymes. This free nature of sulfyhydryl group gets destroyed by oxidation resulting into a formation of a disulfide bond.

26. 2 . Halogenation mechanism Examples of compounds acting by this mechanism are the compounds which are able to liberate chlorine or hydrochloride or iodine. This category of agents act on the peptide linkage & alter it’s potential & property. The destruction of specific function of protein causes death of micro-organisms. Most of the enzymes are proteinous in nature. A protein molecule is composed of a variety of amino acids connected through a peptide (--CONH--) linkage. As hydrochlorites ( Ocl -) are found to chlorinate peptide linkage exert their antimicrobial activity by chlorination of peptide linkages in protein molecules.

27. Protein precipitation : Examples of compounds acting by this mechanism are metal ions( eg .- Astringents) Polar group of proteins binds with metal ions to form complex. The complex formed may be strong chelate leading to inactivation of proteins

28. Characteristics of Antimicrobial agents It should possess antiseptic/germicide activity . It should have rapid onset of action. It should not cause local cell damage. It should not interfere with body defence . It should show no systemic toxicity from topical applications.

29. Iodine Chemical formula : I 2 Molecular wt. – 126.9 Iodine compounds are very common in nature. Sea water is also having traces of combined iodine, which gets absorbed by some specific plants and sea weeds, like Laminaria digitata . Iodine also occurs in the form of sodium iodate . Preparation : It is manufactured by extracting kelp(seaweed’s ash) with water. When the sulphate and chloride of sodium and potassium gel crystalised out, the solution is concentrated, leaving freely soluble sodium and potassium iodide in the mother liquor. Sulphuric acid is added to mother liquor, small amount of thiosulphate and sulphide are allowed to settle down. Mother liquor is decanted and to this MnO2 is added and iodine distills over.

30. Various Iodine preparations Aqueous iodine solution Weak iodine solution Strong iodine solution Povidone iodine solution Tincture of iodine

31. Note on composition of various iodine preparations Aqueous iodine praparation : Synonym : Lugol’s solution It is having 5% w/v of iodine and 10% w/v of potassium iodide in purified water. Composition : Iodine 50 g Potassium iodide 100 g Purified water 1000 ml 2) Weak iodine preparation : Synonym : Tincture of iodine It is having 2% w/v of iodine and 2.5 % w/v of potassium iodide. Composition : Iodine 20 g Potassium iodide 25 g Alcohol(50%) 1000 ml

32. Povidone iodine Povidone iodine is an aqueous solution of povidone iodine. It is a complex produced by the interaction between iodine and povidone (polyvinyl pyrrolidine ). The complex has 10% available iodine. Description : Complex occurs as yellowish brown, amorphous powder and has characteristic odour . Soluble in water and alcohol. The solution is transparent in nature, has reddish brown colour and faint smell of iodine. Action and uses : It is a powerful bactercidal . Used as disinfectant for the skin, wounds, mouth. Effective in management of burns and cut. 4. Important advantage of this preparations over usual iodine preparations are it’s water solubility, non-irritation, less toxic, and non staining nature. It could be easily removed from skin and cuts by washing.

33. Hydrogen peroxide Chemical formula : H 2 O 2 It is an aqueous preparation of hydrogen peroxide. Method of preparation : 1. it is obtained by adding a thick paste of Barium peroxide (BaO 2 ) in ice cold water to a ice cold dilute sulphuric acid. The barium sulpahte will formed. BaO 2 + H 2 SO 4 -------------- BaSO 4 + H 2 O 2 Barium Sulphuric Barium Hydrogen Peroxide acid sulphate peroxide 2. It is also manufactured by electrolysis of ice cold 50% sulphuric acid. 2H 2 SO 4 ----------- 2HSO 4 + 2 H + Perdisulphuric acid is formed, which on distillation under reduced pressure gives hydrogen peroxide 2HSO 4 + 2 H + ----------- H 2 S 2 O 8 ( Predisulphuric acid) H 2 SO 4 + 2H 2 O ----------- H 2 SO 4 + H 2 O 2 3. Prepared by passing CO2 through Barium peroxide in water. BaO 2 + CO 2 + H 2 O --------- H 2 O 2 + BaCO 3

34. Properties : It is colourless and odouless liquid having slightly acidic taste. It is a strong oxidising agent. The solution decomposes in contact with oxidizable matter or when made alkaline. Uses : It is a strong oxidising agent and it gives nascent oxygen. It is used in cleaning cuts and wounds as it is antiseptic and germicide. It is used as deodorant. Used in bleaching the hair. Effective antidote in phosphurus and cyanide poisoning.

35. Storage: It is stored in a light resistant container with a stopper made up of glass or plastic resistant to hydrogen peroxide. It is kept in cool and dark place.

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