Inorganic Pharmaceutical Chemistry: Diarrhea Treatment

Inorganic Pharmaceutical Chemistry

• Gastrointestinal agents commonly used to treat mild diarrhea
• Diarrhea is a symptom, not a disease.
• Factors that impair digestion and absorption lead to increased bulk in the intestinal tract, stimulating peristalsis and causing diarrhea.
• Diarrhea can be acute or chronic, with different causes.
• Dehydration and electrolyte imbalances are complications of diarrhea, particularly for young and elderly individuals.
• Antidiarrheal agents treat symptoms and occasionally causes, but not complications.
• Most antidiarrheal products contain adsorbent-protectives, antispasmodics, and possibly antibacterial agents.
• The ideal antispasmodic agent directly acts on smooth muscles of the gut to decrease peristalsis and increase segmentation.
• Antibacterials are effective when there's an intestinal infection.
• Adsorbent-protectives bind toxins, bacteria, and viruses, and also provide a protective mucosal coating.
• Some adsorbent-protectives include bismuth salts, special clays, and activated charcoal.

Mechanism of Adsorption

• Adsorption: substance (adsorbate) adheres to the surface of another substance (adsorbent).
• Activated charcoal, kaolin, and specific clays act as adsorbents in the gut.

Types of Adsorption

• Physical Adsorption: occurs due to Van der Waals forces, which are weak and non-specific, leading to reversible adsorption.
• Chemical Adsorption: involves stronger chemical bonds between adsorbent and adsorbate, possibly irreversible, with electron exchange or sharing.

Factors Affecting Adsorption

• Surface Area and Porosity: Adsorbents like activated charcoal have high surface areas and porous structures, crucial for adsorbing substances.
• Polarity: Adsorption is influenced by the polarity of molecules. Polar adsorbents bind polar molecules, and non-polar adsorbents bind non-polar substances.
• pH Sensitivity: The surrounding environment's pH affects adsorption efficiency. For example, bismuth salts' solubility and adsorption vary with pH.

Bismuth-Containing Products

• Utilization of bismuth salts as antidiarrheals is mainly based on tradition.
• Bismuth subcarbonate is used as an antacid.
• Bismuth salts are water-insoluble, but a small amount dissolves, acting as a mild astringent and antiseptic.
• Intestinal hydrogen sulfide interacts with bismuth salts to form bismuth sulfide, causing black stools.
• Bismuth compounds provide dual action: they adsorb toxins and bacteria while creating a protective intestinal barrier.

Bismuth Subnitrate

• A white, slightly hygroscopic powder, insoluble in water and alcohol, but soluble in acids.
• Assayed in terms of bismuth trioxide.
• Incompatibility with tragacanth, which can be overcome by adding sodium biphosphate or trisodium phosphate.
• May inhibit pepsin.
• Used as a component of Milk of Bismuth, where it acts as a mild astringent-protective.

Milk of Bismuth

• Contains bismuth hydroxide and bismuth subcarbonate suspended in water.
• Produced by converting bismuth subnitrate to bismuth nitrate, then treated with ammonium carbonate and ammonia solution.
• Classified as an astringent and antacid.

Bismuth Subcarbonate

• White or pale yellowish-white powder, odorless and tasteless.
• Stable in air but affected by light, insoluble in water and alcohol, but soluble in acids.
• Assayed in terms of bismuth trioxide.

Nonofficial Bismuth Compounds

• Bismuth Subgallate
• Bismuth Subsalicylate
• Bismuth Ammonium Citrate

Activated Clays and Other Adsorbents

• Clays with excellent adsorbent properties are used industrially and clinically for mild, short-duration diarrhea.

Kaolin

• Native hydrated aluminum silicate, powdered and free from gritty particles.
• Soft, white, or yellowish-white powder, with an earthy taste.
• Binds toxins and bacteria through physical and chemical adsorption.
• Insoluble in water, acids, and alkali hydroxides.
• Often used with pectin (Kaopectate®, Kao-Con®) as an adsorbent.
• Reported to interfere with intestinal absorption of lincomycin.

Activated Charcoal

• Used as an adsorbent for diarrhea and as an antidote for specific poisoning.
• Works primarily through physical adsorption.
• Highly porous, effectively binding large organic molecules such as toxins, chemicals, and drugs.

Saline Cathartics

• Agents that accelerate and increase bowel evacuation.
• Laxatives are mild cathartics.
• Widely used, but often abused and overpromoted.
• Properly used to:
  • Ease defecation with painful hemorrhoids or rectal disorders.
  • Avoid straining and pressure in patients with hernias.
  • Reduce blood pressure during defecation in patients with hypertension or other circulatory diseases.
  • Relieve acute constipation.
  • Remove solid material before certain roentgenographic studies.
• Sodium-containing saline cathartics are not suitable for long-term use in low-sodium diets.
• Magnesium salts should be restricted for those with impaired renal function due to magnesium absorption and CNS depressant effects.

Official Saline Cathartics

• Sodium Biphosphate:
  • Colorless crystals or white crystalline powder, odorless, slightly deliquescent, acid to litmus.
  • Dissolves in water, dissociating into ions.
  • Used as urinary acidifier and cathartic (Phospho-Soda, Vacuetts, and Sal Hepatica).
• Sodium Phosphate:
  • Colorless or white granular salt, effervesces in moist air, solutions are alkaline.
  • Freely soluble in water, poorly absorbed in intestines.
  • Used as a saline cathartic (Fleet Enema, Phospho-Soda).
• Dried Sodium Phosphate:
  • Nearly anhydrous white powder, absorbs moisture readily, freely soluble in water, insoluble in alcohol.
  • Used as a saline cathartic in Effervescent Sodium Phosphate, a mixture with carbonates, tartaric acid, and citric acid.
  • Dried form prevents premature reactions and ensures a pleasant flavor.