Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics PDF

Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics This group of gastrointestinal agents is commonly used for the treatment of mild diarrhea. Diarrhea is a symptom and not a disease. Very briefly, it results when some factor impairs digestion and/or absorption, thereby incre...

Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics This group of gastrointestinal agents is commonly used for the treatment of mild diarrhea. Diarrhea is a symptom and not a disease. Very briefly, it results when some factor impairs digestion and/or absorption, thereby increasing the bulk of the intestinal tract. This increased bulk stimulates peristalsis, propelling the intestinal contents to the anus. Diarrhea may be acute or chronic. Acute diarrhea can be caused by bacterial toxins, chemical poisons, drugs, allergy, and disease. The effects of these agents range from tissue damage or irritation to that of causing electrolytes to flow from body fluids into the intestinal tract. Chronic diarrhea can result from gastrointestinal surgery, carcinomas, chronic inflammatory conditions, and various absorptive defects. Frequently the causative factor of acute diarrhea is not found, and the patient shrugs it off as a 24- or 48- hour stomach flu. Diarrhea is a serious condition, particularly for very young or elderly patients. The loss of fluids and electrolytes can quickly lead to dehydration and electrolyte imbalances. The antidiarrheal agents described in this chapter will only treat the symptoms and occasionally the cause, but they will not treat the complications. Most products for the treatment of diarrhea will consist of an adsorbent-protective, an antispasmodic, and possibly an antibacterial agent. The ideal antispasmodic agent should act directly on the smooth muscles of the gut to produce a spasm-like effect which decreases peristalsis and increases segmentation. The antibacterials are only effective if there is an actual infection in the intestinal tract or during epidemics previously shown to be caused by a microorganism. The adsorbent- protectives supposedly adsorb toxins, bacteria, and viruses along with providing a protective coating of the intestinal mucosa. They include bismuth salts, special clays, and activated charcoal. 1 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics Mechanism of Adsorption Adsorption is a process by which a substance (the adsorbate) adheres to the surface of another substance (the adsorbent). In the case of gastrointestinal protectives and adsorbents, substances like activated charcoal, kaolin, and certain clays (e.g., attapulgite) act as adsorbents by binding toxins, gases, and bacteria in the gut. Types of Adsorption Physical Adsorption: This occurs due to Van der Waals forces, which are weak, non-specific forces that attract molecules to the surface of the absorbent. Physical adsorption is generally reversible and does not involve chemical bonding. Chemical Adsorption: Involves the formation of stronger chemical bonds between the adsorbent and adsorbate. This type of adsorption can be irreversible and involves the exchange or sharing of electrons between the adsorbent and the adsorbate. For example, bismuth compounds can chemically interact with toxins in the gastrointestinal tract, reducing irritation and inflammation. Factors Affecting Adsorption 1. Surface Area and Porosity: Adsorbents like activated charcoal are characterized by high surface areas and porous structures. For instance, one gram of activated charcoal can have a surface area of over 1,000 square meters. This massive surface area allows for a higher amount of substance to be adsorbed. 2. Polarity: Adsorption is affected by the polarity of the molecules. Polar adsorbents, such as certain clays, will more effectively adsorb polar molecules like water and electrolytes, while non-polar adsorbents like activated charcoal will be more effective at binding non-polar substances such as lipophilic drugs and toxins. 2 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics 3. pH Sensitivity: The pH of the surrounding environment can influence the efficiency of adsorption. For example, the adsorption of bismuth salts can vary based on the pH of the stomach or intestines, as certain compounds become soluble depending on the pH level. Bismuth-Containing Products. The use of bismuth salts as antidiarrheals seems to be supported chiefly by tradition. Bismuth sub carbonate has also found some use as antacid. Although the bismuth salts used as antidiarrheals are water-insoluble, a small amount does go into solution. The soluble bismuth cation supposedly exerts a mild astringent and antiseptic action, but it is doubtful whether this is clinically significant. Intestinal hydrogen sulfide acts upon the bismuth salts to form bismuth sulfide; hence, the black stools resulting from the oral administration of bismuth-containing preparations. These compounds provide a dual action, adsorbing toxins and bacteria while forming a protective barrier in the intestines. 2Bi3+ + 3H2S → Bi2S3 (black precipitate) + 6H+ 1. Bismuth Subnitrate, N.F. XIII (approximate formula: [Bi(OH)2NO3]4·BiO(OH)) Bismuth Subnitrate occurs as a white, slightly hygroscopic powder which gives an acid reaction using blue litmus paper. It is practically insoluble in water and in alcohol but is readily dissolved by hydrochloric or nitric acid. It is assayed in terms of bismuth trioxide (Bi2O3). Bismuth subnitrate has a well-recognized incompatibility with tragacanth, in which tragacanth precipitates as a hard mass in the presence of the salt. 3 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics An interesting paper in connection with this incompatibility points out that the difficulty may be overcome by the protective action of sodium biphosphate or trisodium phosphate. These authors feel that because tragacanth is a negative colloid, the adsorption of the positive bismuth ion (without corresponding adsorption of the negative nitrate ions) tends to precipitate the colloid. The use of phosphates is based on their supplying the negative ions lacking, which may then be adsorbed by the tragacanth, stabilizing the colloid. Bismuth subnitrate apparently can inhibit pepsin. However, its main use is as a component of Milk of Bismuth, where it probably functions as a mild astringent- protective Milk of Bismuth Milk of Bismuth contains bismuth hydroxide and bismuth sub carbonate in suspension in water. It is made by converting bismuth subnitrate to bismuth nitrate [Bi(NO₃)₃] by the addition of nitric acid. Then, by treatment with ammonium carbonate and ammonia solution, bismuth nitrate is converted to bismuth hydroxide and sub carbonate. Chemical Reactions: NH₂CO₂NH₄·NH₄HCO₃ + NH₄OH ⇌ 2(NH₄)₂CO₃ 3(NH₄)₂CO₃ + 2Bi(NO₃)₃ → Bi₂(CO₃)₃ ↓ + 6NH₄NO₃ 2Bi₂(CO₃)₃ + H₂O → [(BiO)₂CO₃]₂·H₂O + 4CO₂ ↑ Bi(NO₃)₃ + 3NH₄OH → Bi(OH)₃ ↓ + 3NH₄NO₃ It is classified by the National Formulary as an astringent and antacid. 4 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics 2. Bismuth Sub carbonate, U.S.P. XVIII (approximate formula: [(BiO)₂CO₃]₂·H₂O) Bismuth sub carbonate is a white or pale yellowish white, odorless, tasteless powder, which is stable in air, but is slowly affected by light. It is practically insoluble in water and in alcohol but dissolves completely in nitric acid and in hydrochloric acid, with copious effervescence. Bismuth sub carbonate is assayed in terms of bismuth trioxide (Bi₂O₃). Nonofficial Bismuth Compounds 1. Bismuth Subgallate 2. Bismuth Subsalicylate 3. Bismuth Ammonium Citrate Activated Clays and Other Adsorbents. This group is composed mostly of clays which have excellent adsorbent properties, and most of them are used for that purpose industrially. They appear to have a valid clinical use, at least in mild diarrhea of short duration. 1. Kaolin Kaolin is a native hydrated aluminum silicate, powdered and freed from gritty particles. It occurs as a soft, white, or yellowish white powder, or as lumps. It has an earthy or clay-like taste. Kaolin binds toxins and bacteria through both physical and chemical adsorption. Kaolin is insoluble in water, in cold diluted acids, and in solutions of the alkali hydroxides. It is usually found together with the vegetable carbohydrate, pectin (Kaopectate®, Kao-Con®) and used as an adsorbent. Kaolin- containing products have been reported to interfere materially with the intestinal absorption of lincomycin. 5 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics 2. Activated Charcoal Activated charcoal has been used as an adsorbent in the treatment of diarrhea. It is now a recommended antidote in certain types of poisoning. It works primarily through physical adsorption. It is highly porous and effective in binding large organic molecules such as bacterial toxins, chemicals, and drugs. SALINE CATHARTICS Saline cathartics (purgatives) are agents that quicken and increase evacuation from the bowels. Laxatives are mild cathartics. Most can be purchased without a prescription and are a group that has been widely used, abused, and often overpromoted by the manufacturer. The 1971 A.M.A. Drug Evaluations states that cathartics are properly used to: (1) ease defecation in patients with painful hemorrhoids or other rectal disorders, and to avoid excessive straining and concurrent increases in abdominal pressure in patients with hernias. (2) avoid potentially hazardous rises in blood pressure during defecation in patients with hypertension, cerebral, coronary, or other arterial diseases. (3) relieve acute constipation. (4) remove solid material from the intestinal tract prior to certain roentgenographic studies. Laxatives should only be used for short-term therapy as prolonged use may lead to loss of spontaneous bowel rhythm upon which normal evacuation depends, causing the patient to become dependent on laxatives, the so-called "laxative habit." Constipation is the infrequent or difficult evacuation of feces. It may be due to a person resisting the natural urge to defecate, causing the fecal material which 6 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics remains in the colon to lose fluid and to become relatively dry and hard. Constipation can also be caused by intestinal atony (lack of muscle tension), intestinal spasm, emotions, drugs, and diet. Basically, there are four types of laxatives: (1) The stimulant laxatives act by local irritation on the intestinal tract, which increases peristaltic activity. They include phenolphthalein, aloin, cascara extract, rhubarb extract, senna extract, podophyllin, castor oil, 1,8-dihydroxyanthraquinone (danthron), oxyphenisatin, bisacodyl, and calomel (no longer used). (2) The bulk-forming laxatives are made from cellulose and other nondigestible polysaccharides. They swell when wet, with the increased bulk stimulating peristalsis. Included in this group are psyllium seed, methyl cellulose, sodium carboxymethylcellulose, and karaya gum. (3) The emollient laxatives act either as lubricants facilitating the passage of compacted fecal material or as stool softeners. Mineral oil is the main lubricant laxative used, and d-octyl sodium sulfosuccinate, an anionic surface-active agent, is the most used stool softener. (4) The saline cathartics act by increasing the osmotic load of the gastrointestinal tract. They are salts of poorly absorbable anions and sometimes cations. The body relieves the hypertonicity of the gut by secreting additional fluids into the intestinal tract. The resulting increased bulk stimulates peristalsis. Poorly absorbed anions that are used as saline cathartics are biphosphate (H₂PO₄⁻), phosphate (HPO₄²⁻), sulfate, and tartrate. The saline cathartics are water soluble and are taken with large amounts of water. This prevents excessive loss of body fluids and reduces nausea and vomiting if a too hypertonic solution should reach the stomach. 7 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics The saline cathartics, when taken for brief periods, are relatively free of side effects. Over a longer term, patients on low-sodium diets should not use the sodium-containing saline cathartics (sodium biphosphate, sodium phosphate, sodium sulfate, and potassium sodium tartrate). For those with impaired renal function, the magnesium salts should be restricted, since some magnesium cation is absorbed. Magnesium has a central nervous system depressant effect. Official Saline Cathartics 1. Sodium Biphosphate occurs as colorless crystals or as a white, crystalline powder. It is odorless and is slightly deliquescent. Its solutions are acid to litmus and effervesce with sodium carbonate. When saline cathartics, like sodium biphosphate (NaH₂PO₄) dissolve in water, they dissociate into their respective ions: NaH2PO4 → Na+ + H2PO4− H₂PO₄⁻ + H₂O ⇌ H₃O⁺ + HPO₄²⁻ Although classified by the National Formulary as a urinary acidifier, it is also used as a cathartic (Phospho-Soda, Vacuetts, and Sal Hepatica). 2. Sodium Phosphate occurs as a colorless or white granular salt which effervesces in warm, dry air. Its solutions are alkaline, with a 0.1 M solution having a pH of about 9.5. It is freely soluble in water and very slightly soluble in alcohol. Because of the poor intestinal permeability of the monohydrate phosphate anion, this product is widely used as a saline cathartic (Fleet Enema, Phospho- Soda). 8 Inorganic Pharmaceutical Chemistry: Protectives, Adsorbents and Cathartics Na2HPO4 → 2Na+ + HPO42− 3. Dried Sodium Phosphate is a nearly anhydrous white powder which readily absorbs moisture. It is freely soluble in water and insoluble in alcohol. It is used as a saline cathartic in Effervescent Sodium Phosphate, which is a mixture of sodium bicarbonate, tartaric acid, and citric acid. When dissolved in water, a carbonated solution of sodium phosphate, sodium tartrate, and sodium citrate is obtained. Sodium tartrate is also a saline cathartic, and sodium citrate provides a lemon-like flavor which, along with the carbonation provided by the carbon dioxide, masks the saline taste. NaH2PO4 + NaHCO3 → Na2HPO4 + CO2 + H2O Dried Sodium Phosphate is used because the heptahydrate salt of Sodium Phosphate would cause a premature reaction between the sodium bicarbonate and tartaric and citric acids, yielding a product with a flat, saline flavor. Best of Luck 9