PHARCHEM LEC

Chapter V: Gastrointestinal Agents

Inorganic agents used to treat gastrointestinal disorders: 1. Products for altering gastric pH 2. Protective for intestinal inflammation 3. Adsorbents for intestinal toxins 4. Cathartics or laxatives for constipation Antacids Alkaline bases used to neutralize excess HCl To inactivate the proteolytic enzyme, pepsin pH 1 when stomach is empty: due to the presence of endogenous HCl; pH 7 if food is present Gastritis: a general inflammation of the gastric mucosa Peptic ulcer: a specified circumscribed erosion o Esophageal ulcer: can be located in the lower end of the esophagus; causes heartburn o Gastric ulcer: stomach; malignancy and hemorrhage are common o Duodenal ulcer: duodenum; perforation Treatment will range from diet and antacid and/or anti-cholinergic therapy to complete bed rest or surgery Criteria: o Should not be absorbable or cause systemic alkalosis o Should not be a laxative or cause constipation o Should exert the effect rapidly and over a long period of time o Reaction of antacid with gastric HCl should not cause a large evolution of gas o Should buffer in the pH 4-6 range o Should inhibit pepsin 1. Sodium Bicarbonate o Highly water insoluble antacid with a rapid onset of action but relatively short duration o Can cause a sharp increase in the pH o Evolution of CO2 = belching and flatulence o Found in many effervescent antacid preparations o Main function: react with an acid with the evolution of CO2 = sparkling flavor 2. Aluminum Hydroxide USP 31 [Al(OH)3 ; 77.98] o Aluminum Hydroxide Gel USP 26 White viscous suspension, from which a small amount of liquid may separate on standing Can contain aromatics and sweetening substances (sucrose, glycerin, saccharin) N.m.t 0.5% of preservative is allowed (sodium benzoate, benzoic acid, methyl paraben) pH: 5.5-8.0 o Dried Aluminum Hydroxide Gel USP 26 White, colorless, tasteless, amorphous powder insoluble in water and alcohol, soluble in dilute mineral acids and solutions of fixed alkali hydroxide Also in tablet form (Tablets USP 26); assayed in terms of their Al2O3 content and acid-consuming capacity Very fine colloidal particle

o Uses

Exhibit a large surface area = great absorptive powers Ideal buffers in the pH 3-5 due to their amphoteric properties

Treatment of hyperchlorhydria and peptic ulcer Indicated for intestinal toxemia Mechanism of its action is attributed to its capability of adsorbing HCl, toxins, gases and bacteria Advantage of a gel: adsorbs pepsin [Calcium Containing Antacids] Action is dependent upon their basic properties; raise pH to 7; tend to be constipating; found in combination with magnesium antacids 3. Calcium Carbonate USP 31 [CaCO3; 100.09] o Fine, white, odorless, tasteless, microcrystalline powder, stable in air o Insoluble in water but solubility is increased in the presence of nay ammonium salt or CO2 o Presence of alkali reduces its solubility o Insoluble in alcohol o Dissolves with effervescence in diluted acetic acid, diluted hydrochloric acid and diluted nitric acid o Uses One of the most popular antacids Action is limited by the amount of salt that will go into solution As gastric HCl acid consumes the solubilized calcium carbonate, more goes into solution USP 26: lozenges and oral suspension 4. Tribasic Calcium Phosphate NF 26 o Aka Precipitated Calcium Phosphate, Tertiary Calcium Phosphate, Calcium Phosphate o Consists of 10CaO3P2O5H2O o After ignition at 800C for 30 mins: contains amount of phosphate n.l.t 90% of tribasic calcium phosphate Ca3(PO4)2 o Found abundantly in nature as phosphorite/phosphite rock and apatite, Ca3(PO4)2CaF2 o White odorless, tasteless powder, insoluble in water and alcohol but dissolves in diluted HCl and HNO3 o Uses Production of primary and secondary phosphate diminishes the hydrogen ion concentration of the gastric HCl = treatment of hyperacidity No gas produced and does not alkalinize the system Source of calcium for the system because of its insolubility [Magnesium Containing Antacids] Poorly soluble salts As the pH of the stomach approaches neutrality = rate of dissolution of Mg salts slows down and stops It is the anion not the Mg cation that confers antacid properties Anions = laxative Usually found in combination with aluminum and calcium antacids to equalize the constipative and laxative actions 5. Magnesium Carbonate USP 31 [Mg(CO3)4Mg(OH)25H2O]

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Aka carbonate of magnesia, magnesium carbonate, heavy magnesium carbonate White, bulky, odorless powder, slightly earthly taste Occurs in friable masses, nearly insoluble to water which imparts a slightly alkaline reaction due to a slight dissociation of the Mg(OH)2 Dissolves with effervescence in dilute acids Uses Antacids properties are due to to the hydroxide and carbonate anions reacting with gastric HCl Limited solubility = dissolves only as carbonate and hydroxide are being consumed

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Magnesium Hydroxide USP 31 [Mg(OH)2; 58.32] o White, bulky powder o Insoluble in water in alcohol but dissolves in acids o Uses Basic character = antacid In high doses: laxative; due to the formation of magnesium chloride in the stomach which exerts a salt action in the intestinal tract Milk of Magnesia o Suspension of magnesium hydroxide, n.l.t 7%, n.m.t. 8.5% o Small amount of citric acid maybe added to minimize the interaction with glass containers o Suitable flavoring agents maybe added o Very popular antacid and laxative Magnesium Oxide USP 31 [MgO; 40.30] o Aka Magnesia o Light Magnesium Oxide (5mL occupies 4050mL); hydrolyzes more easily o Heavy Magnesium Oxide (5 mL occupies 1020mL) o White, odorless powders nearly insoluble in water and in alcohol, dissolves in dilute acid o Absorb CO2 and moisture in air o Uses As a laxative, diuretic, antacid and as arsenic antidote (internally) Should be administered in about 29 times its weight of water to prevent formation of gelatinous mass Should be added to water not the reverse to prevent formation of large lump Magnesium Trisilicate USP 31 [2MgO3SiO2; 260] o Compound of magnesium oxide (n.l.t 20%) and silicon dioxide (n.l.t. 45%) containing varying proportions of water o Fine, white, odorless, tasteless powder, free from grittiness o Readily dissolves in mineral acids o Must have a definite magnesium dioxide/silicon dioxide ratio o Amount of silicon dioxide increase with respect to magnesium oxide = loss in antacid capability o Uses Valuable in peptic ulcer Value depends on this reaction: 2MgO3SiO2xH2O+4H+ -> 3SiO2xH2O + 2Mg+2+2H2O

Colloidal silicic acid/hydrous silica has adsorptive powers and could protect ulcer from further acid and peptic attack, adsorbs the pepsin 10. Magnesium Phosphate USP 31 [Mg3(PO4)25H2O; 353] o Aka Tertiary Magnesium Phosphate o White, odorless and tasteless powder o Readily soluble in diluted mineral acids [Combination Antacid Preparations] Attempt to balance the constipative effect of calcium and aluminum with the laxative effect of magnesium 11. Aluminum Hydroxide Gel Magnesium Hydroxide o Combination: Aludrox, WinGel, Maalox, Cremalin 12. Aluminum Hydroxide Gel Magnesium Trisilicate o Combination: Gelusil, Tricreamalate, Triosgel 13. Magaldrate Chem. Combination of aluminum hydroxide and magnesium hydroxide (Riopan) 14. Simethicone Di-Gel, Mylanta o Added to lessen gas 15. Alginic Acid Sodium Bicarb: Gaviscon, FoamTab Protectives and Adsorbents Commonly used for the treatment of mild diarrhea Some factors impair digestion/adsorption = increasing bulk of intestinal tract = stimulates peristalsis, propelling the intestinal contents to the anus Acute diarrhea: can be caused by bacterial toxins, chemical poisons, drugs, allergy and disease; can cause tissue damage or irritation to that causing electrolytes to flow from body fluids into the intestinal tract Chronic diarrhea: GI surgery, carcinomas, chronic inflammation conditions, carious adsorptive defects Ideal antidiarrheal should act directly on the smooth muscle of the gut to produce a spasm-like effect which decreases peristalsis and increase segmentation [Bismuth Containing Products] Soluble bismuth cation exerts a mild astringent and antiseptic action Intestinal hydrogen sulfide + bismuth salts = bismuth sulfide which results to black stool because of oral administration of bismuth-containing preparations 1. Bismuth Subnitrate USP 31 [Bi(OH)2(NO3)4BiO(OH)] o Aka Basic Bismuth Nitrate, White Bismuth o White, slightly hygroscopic powder, gives an acid reaction using blue litmus o Readily dissolved by HCl o Assayed in terms of bismuth trioxide (Bi2O3) o Incompatible with tragacanth, tragacanth ppts as a hard mass in the presence of the salt, which can be overcome with addition of sodium biphosphate or trisodium phosphate o Uses Effective non-irritant intestinal antiseptic Bismuth salt lessens gastric secretion and reduce acidity = employed in treating gastric ulcers and inflammations Common remedy against diarrhea 2. Bismuth Subcarbonate USP 31 [BiO2(CO3)2H2O o Aka Basic Bismuth Carbonate o White or pale yellowish white, odorless, tasteless powder, stable in air but slowly affected by light o Dissolves in HCl with effervescence

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Assayed in terms of its bismuth trioxide content Uses

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Used for its protective and antacid effect in inflammations of the stomach and bowels Large doses (60g) for rendering the alimentary canal opaque to x-ray Astringent and adsorbent in the treatment of diarrhea Milk of Bismuth USP 31 o Aka Bismuth Magma, Bismuth Cream o Contains bismuth hydroxide and bismuth subcarbonate in suspension in water o Made by converting bismuth subnitrate to bismuth nitrite b addition of nitric acid then treated with ammonium carbonate and ammonia solution, bismuth nitrite is converted to bismuth hydroxide and bismuth subcarbonate o Uses Astringent and antacid Kaolin USP 31 o Aka Porcelain Clay, China Clay, Bolus Alba o Native hydrated aluminum silicate, powdered and freed from gritty particles by elutriation o Contains about 20.9% of aluminum Al2O32SiO22H2O, formed by weathering of feldspar, KalSi3O8 o Soft, yellowish white or whitish powder or in lumps o Earthly and clay-like taste o Assumes a darker color and develops a marked clay-like color when moistened with water o Uses Found together with the vegetable carb, pectin (Kaopectate, Kao-Con) Employed as a protective and adsorbent in diarrheal disorders Products with kaolin have been reported to interfere materially with the intestinal absorption of lincomycin Activated Charcoal USP 31 o Adsorbent in the treatment of diarrhea o Antidote in certain types of poisoning

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Saline Cathartics (Purgatives) Agents that quicken and increase evacuation from the bowels; taken with lots of water = prevents excessive loss of body fluid and reduces nausea and vomiting 1972 AMA Drug Evaluations criteria for proper use of cathartics: o Ease defecation in patients with painful hemorrhoids or other rectal disorders o Avoid potentially hazardous rises in BP during defacation o Relieve acute constipation o Remove solid material from the intestinal tract Laxatives o Should only be used for a short term therapy; prolonged use leads to loss of spontaneous bowel rhythm; laxative habit o 4 Types Stimulant: act by local irritation on the intestinal tract, which increases peristaltic activity

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Bulk-forming: made from cellulose + other non-digestible polysaccharides; swells when wet; increased bulk stimulates peristalsis Emollient: Ex. Mineral Oil Saline Cathartics: act by incrasing the osmotic load of the GI tract; salts of poorly absorbable anions (biphosphate, phosphate, sulfate, tartrate), sometimes cations; body relives the hypertonicity by secreting additional fluids in the intestinal tract *Soluble salts are cathartic due to the poorly absorbed Mg ion Monobasic Sodium Phosphate USP 31 [NaH2PO4H2O] o Aka Sodium Dihydrogen Phosphate, Sodium Acid Phosphate, Primary Sodium Phosphate, Sodium Biphosphate o Colorless crystalline powder, odorless, slightly deliquescent o Solution is acid to litmus due to the acid dihydrogen phosphate anion o Effervescent with sodium carbonate o Uses Urinary acidifier Used to render the urine acid in case of cystitis with hexamethylenetetramine (Methenamine), as ithis substance decomposes into formaldehyde only in the presence of acids Dibasic Sodium Phosphate USP 31 [Na2HPO4H2O; 268.07] o Aka dibasic Sodium Phosphate, Disodium Hydrogen Phosphate, Secondary Sodium Phosphate o Colorless or white granular salt which effervesces in warm dry air o Alkaline to litmus and phenolphthalein with a ph of 9.5 o Official with one, two, seven, or twelve moles of water of hydration o Uses Saline cathartic because of the poor intestinal permeability of the monohydrogen phosphate ion *CAUTION: should never be confused with the commercial tribasic sodium phosphate which is very alkaline and caustic Potassium Sodium Tartrate USP 31 [KNaC4H4O64H2O; 282.23] o Aka Rochelle Salt, Seignette Salt o Colorless crystals or white crystalline powder, cooling saline taste o Often coated with a white powder because it effloresces slightly in warm, dry air o Uses Active cathartic with little pain or nausea and produces watery stool Has a disagreeable bitter taste which can be lessened by administering the solution in an ice-cold condition Parentally: as an anticonvulsant Also used in its saturated solution for its anesthetic effect in sprains and bruises Antiphlogistic action

Magnesium Citrate USP 31 o Aka Citrate of Magnesia, Purgative Lemonade o Made by reacting magnesium carbonate with citric acid, then adding flavoring agents, sodium or potassium bicarb is then added to react with the remaining citric acid yielding a palatable, carbonated, lemon-flavored solution o Must be sterilized or pasteurized [Non-official Saline Cathartics] 5. Sodium Sulfate: Aka Glaubers Salt 6. Potassium Phosphate: Aka Dibasic Potassium Phosphate, Dipotassium Hydrogen Phosphate,DKP 7. Potassium Bitartrate: Aka Cream of Tartar, Potassium Acid Tartrate, Potassium Hydrogen Tatrate 8. Calomel: Aka Mercurous Chloride, Mild Mercury Chloride

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CHAPTER VI: TOPICAL AGENTS

Used on body surfaces Penetration of an antiseptic compound into tissues below the wound = prevention of deep infections Topical applications maybe accomplished within body cavities that open to the outside (oral, nasal, otic, vaginal, colonic cavities); systemic absorption from these areas is route of systemic administration (buccal tablets, suppositories) Protectives Substances which maybe applied to the skin to protect areas from irritation Desirable properties o Insolubility: limits the absorption of the compounds through the skin, makes it difficult to wash them off and diminish metallic properties on tissues o Chemically inert: necessary in order to prevent the interaction between the protective substance and the tissue Efficient adsorbents useful for adsorbing moisture from the surface of the skin Protective and adsorbent action is maximized with decreasing particle size; small particle = larger surface area Fine state of subdivision of the particle = smooth substance which aids in preventing irritation due to rubbing or friction Available for use internally for GI irritations Should not be used on abraded skin because it will mix to the exudates and dry to a crust which adhere to the open tissue Protective Products 1. Talc USP 31 [3MgO4SiO2H2O] o Aka French Chalk, Soapstone; Piedra GRASSA; Creta Gallica o Native, hydrous magnesium silicate sometimes with a small proportion of aluminum silicate o White or grayish white crystalline powder o Unctuous, adheres readily to the skin o Layered silicate, softest mineral known o Smooth, greasy feeling to the touch o Soapstone: in its lump form (steatite) o Foliated talc: for cosmetic and pharmaceutical purposes; plate-like structure o Odorless, tasteless, very low adsorptive properties (Important consideration for its use as a filtering aid)

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Inert, unctuous nature = useful lubricating, protective dusting powder Can produce sterile abscesses or granulomas (nodule of inflamed tissue in which granulation is occurring) when applied to broken skin Absorbable talc powder should be used on surgical gloves Zinc Oxide USP 31 [ZnO; 81.37] o Aka Zinc White, Lana o Algodon Filisoficos; Flores de Zinc o Manufactures by heating in a furnace a mixture of coke + a zinc mineral; free metallic zinc is liberated and vaporized then vapors are passed up to a tower where a strong current of air is encountered and burns forming ZnO Calamine [Zn2SiO4H2O] Willemite [Zn2SiO4] Smithsonite [ZnCO3] Franklinite [ZnO, admixed with oxides of iron and manganese] Zincite [ZnO, red variety] o Medical grade: calcinations of zinc carbonate in a shallow vessel o Fine, odorless, amorphous white or yellowish white powder, free from gritty particles o Gradually absorbs CO2 from the air to form basic zinc carbonate o Reacts with dilute acids and aqueous solutions of ammonium compounds to form water soluble products o When treated with dilute HCl: oxide forms the Lewis acid, zinc chloride o Uses Astringent and topical protective Mild astringent and weak antimicrobial compound Release of a small amount of zinc ion from hydrolysis = antimicrobialastringent action As a protective in ointment, pastes and dusting powders in treating skin ulceration Primary ingredient of Calamine USP Calamine USP 31 [ZnOFe2O2] o After ignition, it contains n.l.t. 98%, n.m.t. 100.5% of ZnO o Presence of ferric oxide: pink color (varies according to the method of preparation and amount) o Fine powder, odorless and tasteless o Almost completely soluble in mineral acids o Official forms: ointment, paste, with salicylic acid paste o calamine: originally attributed to the native zinc carbonate; at the present: native form of zinc silicate monohydrate o Uses Topical protective, dusting powders, ointments and lotion (Calamine Lotion USP) Difference between ZnO and calamine: calamines better cosmetic acceptability For dermatological problems involving the exudation of fluids

Uses

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Calamine Lotion USP: equal quantities of Calamine and Zinc Oxide suspended with the aid of Bentonite Magma in a solution of calcium hydroxide Phenolated Calamine Lotion: contains 1% liquefied phenol (provides a local anesthetic and antipruritic action) Zinc Stearate USP 31 o USP 26: compound of zinc with a mixture of solid organic acids from fats and consists of variable proportions of zinc stearate and zinc palmitate; n.l.t. 12%, n.m.t. 14% ZnO o Fine, white, bulky powder, free from grittiness, faint characteristic odor, unctuous to touch, readily adheres to the skin o Can be hydrolyzed by heating in dilute mineral acids to form a soluble zinc salt and an insoluble oily layer of stearic acid o Uses Mild astringent and antimicrobial properties Employed in dusting powders and ointments as a protective Not wetted by moisture = more desirable in dermatological problems where large amounts of fluids are exuded Inhalation of dust can cause pulmonary inflammation; not for infants and children Lubricant in the manufacture of tablets Titanium Dioxide USP 31 [TiO2; 79.90] o White amorphous, odorless, tasteless, infusible powder o 1:10 aqueous suspension is neutral to litmus paper o Soluble in hydrofluoric acid and in hot concentrated sulfuric acids o + potassium bisulfate or alkali carbonates/hydroxides = soluble in water o Reaction of TiO2 with H2O2 in dilute sulfuric acid produces titanium peroxide (TiO3) which imparts an orange-red color o Uses Official category: topical protective Primarily for its opacity due to its high refractive index High refractivity = useful for screening out ultraviolet reaction = presence of Titanium Dioxide in sun screens As a solar ray protective: 5% to 25% in ointments and lotions White pigment in cosmetic and paints White color can be toned down by adding a small amount of iron (III) compounds Silicon Polymers o Inert protective substances, liquid form, known as silicone oils o One polymer is known as Dimethicone or Simethicone USP 26: used in ointments and creams as a water repellent and protective against contact irritants; 30% Simethicone o Adhere very well to the skin, exclude contact with air

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Antimicrobials and Astringents Mechanisms of action: o Can be divided into 3 general categories: oxidation, halogenation and protein precipitation: represent the primary reactions that occur between the agent and the microbial protein can result in the death of microbe or inhibit growth o Site of action of inorganic compounds are nonspecific 1. Oxidation Capable of functioning as antimicrobial agents through oxidative mechanism H2O2, metal peroxides, permanganates, halogens, certain oxohalogen anions Effective oxidative action: reducing groups present in most proteins (ex. Sulfhydryl SH) Formation of the disulfate bridge will alter the proteins function Overall change or destruction of function is responsible for the ultimate destruction of the microorganism Chemical result of oxidizing the protein is reduction of the antimicrobial agent 2. Halogenation Reaction occurring with antiseptic of the hypohalite type and hypochlorite, OCl These types of compounds can serve as reagents in the chlorination of primary and secondary amides = similar reaction can take place under appropriate conditions with the peptide linkage between the amino acid groups comprising the protein molecule Substitution of chlorine atom for the hydrogen produces change in the forces (hydrogen bonding) responsible for the proper conformation of the protein molecule; In oxidation: changes in confirmation results in destruction of function 3. Protein Precipitation Involves the interaction of proteins with metallic ions having large charge/radius ratio or strong electrostatic fields Property is available in transition metal cations (Grp. I-B, Grp. II-B); Aluminum is also effective due to its charge and small ionic radius Various polar groups on the protein act as the ligands Complexation of the metal results in the radical change in the properties of the protein or protein precipitant Interaction of metal ions with protein is nonspecific, in specific concentration: will react with host as well as microbial protein Protein precipitant properties of metal cations can be altered according to the concentration at the site of action By increasing concentrations, antimicrobial, astringent, irritant and corrosive properties are available [Astringent] Application of very dilute solution of a metal cation to tissue primarily provides a local or surface protein precipitant action Being a surface phenomenon, it doesnt destruct tissue shrinkage or firming of tissues [Control of Antimicrobial/Astringent Action] Largely non-specific in their actions and proteins Action is determined by the concentration

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Soluble compounds maybe controlled by making appropriate concentrations and by placing them in a vehicle which will slow their release to the site For some compounds, this can be accomplished by placing then in solutions with glycerin Complexation with a ligand (Povidone-Iodine) also provides a controllesd release, minimizing toxicity and activity at host cells Insolubility of the compounds makes the formulation of preparation somewhat easier from the standpoint of controlling activity Hydrogen Peroxide Solution USP 31 [H2O2; 32.02] o Aka hydrogen Peroxide, Agua Oxigenada o In each 100mL, n.l.t. 2.5g, n.m.t. 3.5g o Clear, colorless liquid, maybe odorless or may have an odor resembling that of the ozone o Acid to litmus, produces a froth in the mouth when tasted o Pure: colorless, syrupy liquid with astringent properties o When heated to 100C, pure hydrogen peroxide decomposes explosively to form water and oxygen o Deteriorates upon standing and rapidly decomposes when in contact with many oxidizing/reducing substances o To make it more stable: should be kept in a cool place protected from light and dust; preservatives such as acetanilide is added; may be stabilized with any organic and inorganic acids o Weak acid in aqueous solutions o Complexing or chelating agents will chelate trace amounts of abundant metals, making them unable to catalyze decomposition o Adsorbents will remove impurities o Uses Mild oxidizing antiseptic Catalase: catalyzes the decomposition of Hydrogen peroxide to water and oxygen (evolution of O2 gas = bubbling, effervescence) Oxygen acts as oxidizing agents on bacteria Major difficulty: rapidity of oxygen release under the influence of catalase Antiseptic action does not penetrate below the surface to which it is applied Major benefit: cleansing action provided by the foaming release of oxygen Official solution: 3%, 10 volume solution; 6% (20mL) for hair and fabric bleach Undiluted for its antiseptic and cleansing effect on wounds Used as a gargle or mouthwash for bacterial infections of the throat and mouth Half-strengths: vaginal douche Tends to lose its antiseptic property when diluted to less than half-strength Potassium Permanganate USP 31 [KmnO4; 158.04] o Aka Mineral Chamaleon o Odorless, dark purple crystalline compound o Crystals are almost opaque in transmitted light and of blue metallic luster in reflected light

Concentrated solutions: deep violet-red color; highly diluted solutions: pink o Solutions have a sweetish astringent taste o Strong oxidizing agent both in dry state and solution o Caution: Observe great care in handling potassium permanganate, as dangerous explosions may occur if brought in contact with organic or other readily oxidizable substances, either in solution or dry state o Dry state + charcoal = explosive mixtures o Dry state + glycerin = fire o Will also oxidize alcohol o Acid solutions react to reduce the permanganate ion, MnO4- to the mangous ion (Mn2+) with the evolution of oxygen 2KMnO4 + 3H2SO4 -> K2SO4 + 2MnSO4 + 3H2O + 5 (O) o Neutral or alkaline solutions produce a similar reaction with the characteristic brown precipitate of MnO2 2KMnO4 + H2O -> 2MnO2 + 2KOH + 3 (O) For therapeutic importance since potassium permanganate is usually applied to the skin as a neutral aqueous solution o Antimicrobial action is dependent upon its oxidation of protein or other bio-organic substances in neutral media o Manganese dioxide formed as the permanganate is reduced, leaves a brown stain on the skin and tissues o Activity is not selected o Activity on microorganisms is decided diminished in the presence of extraneous organic substances o Uses Not used for both antibacterial and antifungal actions Short duration of action, low penetrating power and slightly staining of the skin = preparation has been declined Solutions are primarily used for skin infections (dermatitis) caused by bacteria and fungi, for plant poisoning and animal toxins Wet dressings prepared from a 1:10,000 solution for vesicular stage of eczema, athletes foot (Tine pedis) and fungal infections (Groin: Tine curries) More effective when applied directly, dressing material might inactivate the permanganate [Chlorine-Containing] Germicidal through the formation of HOCl 3. Sodium Hypochlorite Solution USP 31 [NaOCl; 72] o Aka Dakins Solution, Chlorinated Soda Solution o Contains n.l.t. 4%, n.m.t. 6& by weight of NaOCl o Clear pale greenish yellow liquid, having an odor of chlorine o Solution is affected by light o Alkaline pH coloring red litmus to blue, chlorine will later bleach the color o

Common household bleach: 4.5%-5.0% solution of NaOCl o Disinfectant o Caution: this solution is not suitable for application to wounds o Alkalinity and oxidizing action is too strong for use on tissue; dissolves blood clot and delay healing o Diluted form: Labarraques Solution; consists of sodium hypochlorite solution diluted with equal volume of water (approx. 2.5% NaOCl); disinfectant for inanimate objects o Loses active chlorine and product upon exposure to air o Deterioration also takes place on keeping, heat and light o Decomposed even by dilute and weak acid o Primary component of Clorox o Uses Laundry bleach Germicidal agent 4. Diluted Sodium Hypochlorite Solution o Solution of chlorine compounds of sodium containing in each 100mL, n.l.t. 450mg, n.m.t. 500mg (0.5%) of NaOCl o Colorless or light yellow liquid, slight odor suggesting chlorine o Prepared by diluting sodium hypochlorite solution with 5x the quantity of water and adjusting the pH with 5% solution of sodium bicarbonate = pH of 8.3 or less o Due to reduced concentration and pH, resulting solution is used only for local application to tissues as an antibacterial o Dilution of household bleach does not normally meet the USP standards as an antiseptic because of the lack of pH adjustment o Uses Antiseptic on pus-forming wounds Irritation solution for infections inside certain body openings Effective as an antiseptic and at removing necrotic tissue Disadvantage: dissolving certain types of sutures and dissolving blood clots and prolonging clotting time = secondary hemorrhage Foot bath in prevention of various fungal infections [Other Chlorine-Containing Compounds (5&6)] 5. Chlorinated Lime Bleaching powder, chlorine of lime o Chemically calcium chloride hypochlorite [CaOCl(Cl)H2O o Product obtained by passing chlorite gas over slaked lime o Has a distinct odor of chlorine o Decomposes in the air to release hypochlorous acid o Disinfectant in swimming pools and sterile rooms and as a bleaching agent 6. Chloramines o Organic amines with one or two chlorine atoms bonded to the nitrogen o Slowly hydrolyze to release hypochlolous acid when dissolved in water o Products are used as disinfectants and in the purification of drinking water (Chloramine-T and Halazone) o

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Antimicrobial action is that when chlorine gas is dissolved in neutral or acidic water, hypochlorous acid is formed Cl2 + H2O -> HCl _ HOCl o Basis of using chlorine as disinfectants o Antimicrobial action is due to the presence of HOCl Iodine USP 31 (I; 125.90) o Aka Iodinum, Jodum o Heavy, grayish, black plates or granules, having a metallic luster and a characteristic penetrating odor o Very slightly soluble in water (1 in 2950), soluble inalcohol (1 in 12.5) and in solutions of iodine, freely soluble n carbon disulfate and chloroform o Solubility in solutions of iodide (ex. Sodium iodide) is due to the formation of the triiodide (I3-) o Most notable chemical property in aqueous solution is that of a mild oxidizing agent; less reactive than chlorine o Oxidizing action is mediated through the formation of hypoiodous acid (HIO) I2 + H2O -> HI + HIO HIO -> HI + (O) o Free iodine is about six times more effective that hypoiodous acid, HIO o Iodine will oxidize iron to form ferrous iodide = metal spatulas should be protected against pitting by using weighing papers o Toxicity of preparations containing free iodide is frequently mentioned and somewhat overstated o Very active element and is therefore easily inactivated by organic materials in the GI tract; very little free iodine is absorbed o Most toxicity due to ingestion is a result of corrosive action of the element in the GI tract, producing abdominal pains, gastroenteritis and bloody diarrhea o Treatment involves gastric lavage with a soluble starch solution or administration of a 5% sodium thiosulfate solution o Starch solution forms a complex with the iodine, thus aiding in its removal from starch (blue vomit) o Iodine Solution and Iodine Tincture: most frequently used preparations for antimicrobial purposes In each 100mL, n.l.t. 1.8g and n.m.t. 2.2g of Iodine; n.l.t. 2.1g, n.m.t. 2.6g sodium iodide (NaI) Differ only in the nature of the solvent: Iodine Solution is aqueous having been prepared with purified water, Iodine Tincture contains approx.. 50% alcohol as the final solvent Transparent, reddish brown color, characteristic odor of iodine (Iodine Tincture has an alcohol odor) Active antimicrobial agent common to both is iodine o Uses Most effective topical antiseptic agents available Antiseptics to skin prior to surgery Iodine Tincture may be more suitable for surgery since alcohol seems to o

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improve penetration of the iodine due to a wetting or spreading effect Can be diluted with water to provide effective solutions or reduced concentration for wounds Alcohol in tincture is very irritating to open wounds = reason for stinging Effective against bacterial and fungal infections of the skin Tincture: disinfect drinking water; 3drops/quart will destroy amoebae and bacteria in 15 minutes Both are available in official concentration (2%) and can be diluted to 0.5% to 1% for application to wounds and 0.1% for irrigation Povidone-Iodine USP 31 o Complex of iodine with povidone (polymer also known as polyvinylpyrrolidone or PVP) o Contains n.l.t. 9& n.m.t. 12% of available iodine o Yellowish brown amorphous powder and has a slight characteristic odor o Aqueous solution is acid to litmus o Insoluble in organic solvents o Member of a class of compounds referred to as iodophors o Iodophors: complexes of iodine, with carrier organic molecules serving as solubilizing agent; these complexes slowly liberate iodine in solution o Development of iodophore: effort to prepare less irritating iodine products without losing antimicrobial effectiveness o Uses Same uses as iodine solution and tincture Not to be as effective as aqueous or alcoholic solutions of elemental iodine Major advantage: lack of tissue irritation = useful for application to sensitive areas and mucous membranes Solutions are recommended for surgical scrubs and preoperative antisepsis of the skin Used in gargles and mouthwashes for the treatment of infections in the oral activity (Vincents angina) Aerosol: 0.5%; solutions: 1%; surgical scrub: (0.75%); vaginal douche (1%) Silver Nitrate USP 31 [AgNO3; 169.87] o Aka Azotas Argentious, Cristales Lunares o Colorless or white crystals which become gray or grayish black on exposure to light in the presence of organic matter o Sparingly soluble in alcohol o When a protein is treated with a solution containing a soluble silver salt, a heavy ppt is formed involving a complex interaction between the silver ions and proteins; this type of reaction is the basis for the direct antimicrobial action of silver compounds o The protein precipitant action of silver is not selective and will precipitate both bacterial and human protein o Antibacterial, astringent, irritant, corrosive (depending upon the concentration applied)

When applied to tissues: 0.1% Ag+; activity is rapidly bactericidal; action is somewhat localized due to precipitation with tissue proteins and chloride ions in the tissue fluids; bactericidal effect continues after the initial application due to slow production of silver ions from the silver proteinate and silver chloride this sustained action at the tissue level has given rise to colloidal products of silver proteinate and halides as antimicrobial o Silver: olilgo-dynamic action = active in small quantities; found in distilled water that has been in contact with metallic silver = bactericidal to suspentions heavy in viable organisms o Leathal action required a few hours, but water treated in this way, eg distilled through silver condenser, will remain sterile for a long period of time o Extended use of silver preparations = darkening of the skin due to the deposition of free silver below the epidermis (arygria) o Uses Antimicrobial in solutions ranging in concentration from 0.01% to 10% Higher/10%: astringent and irritant properties to the tissue 10. Silver Nitrate Ophthalmic Solution USP 31 o 1% solution for instillation into the eyes of newborn babies o Silver salts: effective against gonococcal organisms o Two drops of this solution are placed in each eye as a prophylactic measure against infections produced by these organisms (Ophthalmia Neonatorum) o Shown to be more effective than antibiotics such as penicillin o USP allows buffering of the Ophthalmic Solutions with sodium acetate and the ph should be between 4.5 and 6 o Available in wax capsules containing about 0.3mL, should be discarded after use o Most recent important use: application of 0.5% aqueous solution in the form of wet dressing on burned areas of patients suffering from third degree burns, because silver ion seemed to be particularly effective at reducing infection due to Staphylococcus aureus, varius species of Proteus and Pseudomonas aeruginosa o Side effects: electrolyte imbalance due to the precipitation of chloride 11. Toughened Silver Nitrate USP 31 o Aka Lunar Caustic, Silver Nitrate Pencils o Made by adding to silver nitrate 4% of its weight of HCl, melting the micture at a low temp. as possible and casting in silver molds o Presence of about 5% silver chloride toughens the silver nitrate = lessens the friability of the pencils o Used as escharotic and germicide for small septic wounds and ulcers 12. Ammoniated Mercury USP 31 [Hg(NH2)Cl; 252] o Aka White Precipitate o White, pulverizable pieces or as white, amorphous powder, odorless, stable in air, darkens on exposure to light o Readily dissolves in HCl, HNO3, HAc o

Prolonged contact with water = formulation of a yellow basic compound which necessitates the use of oils in lotions o Antiseptic action of mercury on microorganisms and body tissues is due to the mercuric ion, which will react with many polar group on the amino acids of proteins but has a particular affinity for sulfhydryl (-SH) groups o Inhibition of bacterial sulfhydryl containing enzymes by the metal ions = inhibition in metal growth and function o Uses Local anti-infective Topically: 5% ointment to skin 3% ophthalmic ointment to conjuctivas Not given internally because of its toxicity 13. Sublimed Sulfur USP 31 o Aka Flowers of Sulfur, Azufre o Fine, yellow, crystalline (rhombic) powder, faint color and taste o One gram dissolves slowly and usually incompletely in about 2mL of carbon disulfide o Obtained by condensing the sulfur vapors produced by heating any form of sulfur 14. Precipitated Sulfur USP 31 o Aka Milk of Sulfur o Prepared by micing sulfur with metal hydroxides to form mixtures of metal sulfides and thiosulfates; sulfur can be precipitated by addition of acid such as HCl o Very fine, pale yellow, amorphous or rhombic powder without odor or taste o Solubility in carbon disulfide is the same with sublimed sulfur o Uses Both forms: scabicides Used in Sulfur Ointment USP at a concentration between 9.5% to 10.5% Treatment of scabies, kills the mite sarcoptes scabiei Sulfur: dermatological agent in the treatment of seborrhea (abnormal secretion of sebum oily/scaly appearance to the skin), acne, psoriasis, etc Keratolytic agent Activity of sulfur is one of loosening and softening horny elements and the scaly formation of sebum and removing them from site = symptomatic treatment for many dermatological problems 15. Sulfurated Potash o Aka Liver of Sulfur o Mixture composed chiefly of potassium polysulfides and potassium thiosulfate o N.l.t. 12% of sulfur n combination as sulfide o Irregular, liver brown pieces when freshly made, changing to a greenish yellow color o Odor of hydrogen sulfide and bitter, acrid and alkaline taste o Uses Official as a pharmaceutical aid as a source of sulfide Used in the preparation of White lotion As a parasiticide (scabicide) Treatment of acne and psoriasis o

16. Selenium Sulfide o N.l.t. 52%, n.m.t. 55.5% of selenium o Bright orange powder, no more than a faint odor o Insoluble in water and organic solvents o White selenium: toxic in large quantities; appears to be an important nutrient in trace amounts o Selenium is not well absorbed through the skin = topical application to limited areas of unbroken, unirritated skin will not usually result in selenium toxicity o Uses Used in shampoos in concentration 1% to 2.5% as an anti-seborrheic Normal method is applying topically on the scalp and letting it stay there for 5 minutes before washing it out Hands should be thoroughly washed and fingernails meticulously cleanses after due to the danger of introduction into the eyes 17. Antimony Potassium Tartrate USP 31 [(SbO)KC4H5O61/2H2O o Aka Tartar Emetic o Formaly used as an emetic and expectorant (Brown Mixture) o Official category and only rational use is as treatment of schistosomiasis o Drug of choice in infections produced by Schistosma japonicum o Stibophen: effective against Schistosoma haematobium and Schistosoma mansoni but less effective against Schistosoma japonica o May be given orally but intravenous doses are more effective Astringents Protein precipitants of limited penetrative power Able to coagulate protein primarily on the surface of cells The general constriction of tissue, e.g. small blood vessels (smooth muscles) then occurs under the influence of the astringent but the action is controlled by virtue of being topical, lacking deeper effects Uses for astringent compounds Styptic to stop bleeding from small cuts by promoting coagulation of blood and constriction of small capillaries Antiperspirant decrease secretion of perspiration by constricting pores at the surface of the skin Restriction of the supply of blood to the surface of mucous membrane as a means of reducing inflammation Direct actions on skin to remove unwanted tissues: requires a higher concentration or a stronger protein precipitant, sometimes termed as corrosives 1. Alum USP 31 [AlNH4 (SO4)212H2O; 453.33] [AlK(SO4)212H2O; 474.39] o Aka Tawas, Ammonium Alum, Potassium Alum o Can be either aluminum ammonium sulfate or aluminum potassium sulfate o Large, colorless crystals, crystalline fragments or as white powder o Odorless, has a sweetish, strongly astringent taste o Slowly soluble in glycerin and insoluble in water

Source of aluminum ion = useful topical astringent High astrinfency of the compounds makes it possible for certain preparations to be used as irritants or caustics Can be used in footbaths = means of toughening the skin and avoid formation of blisters Frequently the active ingredient in styptic pencils, used to stop bleeding from small cuts Protein precipitant properties of Alum are used in the preparation of several biological products, e.g. precipitated diphtheria and tetanus toxoids 2. Aluminum Chloride USP 31 [AlCl36H2O; 241.43] o White or yellowish white deliquescent, crystalline powder o Nearly odorless, has a sweet, very astringent taste o Hydrolysis still form an acidic solution due to HCl which is irritating to tissue o Adjustment of pH to neutral/alkaline range = reduce the irritation but will also reduce the concentration of aluminum ion by precipitating it as aluminum hydroxide = astringent action will be reduced, since it is a property of free aluminum ion o Uses Local external astringent and mild antiseptic Used in aqueous solution in concentration ranging from 10% to 25% Initially used as an antiperspirant but was found to be irritating to sensitive tissues and also damaged clothing due to the formation of HCl by hydrolysis so it has been replaced by aluminum hydroxychloride which is less acidic and less irritating as antiperspirant Ex. Arrid, Right Guard [Other Aluminum-Containing Astringents] 3. Aluminum Sulfate USP 31 [Al 2(SO4)314H2O; 594] o Aka Cake Alum, Pickle Alum, Pearl Alum, Papermakers Alum 4. Aluminum Acetate Solution USP 31 o Yields from each 100mL, n.l.t. 1.2g, n.m.t. 1.45g aluminum oxide and n.l.t. 4.24g, n.m.t. 5.8g of aluminum acetate o Maybe stabilized by the addition of n.m.t. 0.6% boric acid [Zinc-Containing Astringents] 5. Zinc Chloride USP 31 [ZnCl2; 136.28] o Aka butter of Zinc o White, odorless, crystalline powder or granules o Very deliquescent salt o A 1% to 10% solution is acidic to litmus o Solution in water or alcohol is usually slightly turbid but turbidity disappears when a small quantity of HCl is added o Uses Astringent and dentin desensitizer Strong astringent properties makes the compound useful as an escharotic, more caustic than astringent action

Uses

6.

Zinc Sulfate USP 31 [ZnSO47H2O; 287.54] o Aka White Vitriol o Colorless, transparent prisms or as small needles o Odorless and effloresces in dry air o Aqueous solutions are acid to litmus due to hydrolysis of the salt o Uses Externally as an ophthalmic astringent in 0.25% solution Acidic nature requires buffering which can be achieved by additions of borate buffer system (Gifford Buffer System)

Chapter XII: Dental Products

Anticaries Agents Formation of carries (tooth decay) is attributed to the action of acids mostly lactic, obtained from oral bacterial metabolism of dietary carbohydrates Build-up of plaque on the tooth surface = aids the decay process by forming particles or crevices on the teeth surface in which food particles can lode and can be degraded by the bacteria of the mouth One objective of brushing: remove materials from the tooth surface before it hardens into calculus; smooth surface = difficult adherence of food particles and bacteria Flossing and brushing accompanied by fluoride Fluoride in solution or in rapidly soluble salts is deposited in the bone or developing teeth Concentration of fluoride: surface later of enamel > inside (?) Too much fluoride: dental fluorosis (mottled enamel) Enamel of mottled teeth: chalky and soft indicating a loosely bound structure Dental fluorosis occurs in area where fluoride conc. Of drinking water exceeds 2 pp. Lethal adult dose: 2-5g, as compared to the average ingestion of 2.2mg NaF/day of its equivalent in drinking water containing 1ppm fluoride Mechanism by which fluoride inhibits carries formation Fluoride decreases the solubility of enamel in aced Bacterial inhibition hypothesis which is based on the enzyme inhibitory properties of fluoride Fluoride administered by two routes: orally and topically; oral route places fluoride into systemic circulation allowing the fluoride to lay down unerupted teeth as they are formed Most convenient dosage form: fluoridation of the public water supply; usually done by adding sodium fluoride or a luorosilicate, yielding a fluorine concentration of 0.7 to 1ppm Equivalent to an average faily intake to 2.2mg of NaF based on a person drinking six 6-oz glasses of water 1. Sodium Fluoride USP 31 [NaF; 41.99] o White, odorless powder o Uses Official solely as dental prophylactic agent 2% solution have been widely used topically Usual procedure is a series of 4 treatments given several days beginning at the age of 3 for the deciduous teeth Other application are then given at ages 7, 11 and 13

Stannous Fluoride USP 31 [SnF2; 156.69] o Aka Tin Difluoride o White crystalline powder, bitter salty taste o Melts at about 213C o Uses Extensively used for topical fluoride application Simple application of a freshly prepared 8% solution at 6 to 12 months intervals used Requires only one application per treatment as compared to 4 applications per treatment of NaF Applied to cleaned, dry teeth Dentrifices 1. Pumice USP 31 o Aka Pumice Stone, Piedra Pmez o Substance of volcanic origin consisting chiefly of complex silicates of aluminum, potassium and sodium o Very light, hard rough porous grayish masses or as gritty gray powder o Several grades of fineness Pumice Flour or Superfine Pumice Fine Pumice Coarse Pumice o Odorless and tasteless, stable in air, not attacked by acids o Uses Dental abrasive

2.

Chapter VIII: Miscellaneous Inorganic Pharmaceutical Agents

Inhalants 1. Oxygen USP 31 [O2; 32] o Aka Dephlogisticated Air, Aire Vital, Fire air, Aire Puro o Fractional Distillation of Liquid Aire (Linde Process) Air is liquefied by a combination of low temp. and high pressure If compressed air is allowed to expand through a valve = heat is absorbed and the gas is cooled By alternate compression, cooling and expansion of air, the temp. is continuously lowered until it becomes liquid During cooling: water vapor and carbon dioxide in the air condense to liquid and are removed; when liquid is distilled, first portion of vapor is richer in the lower boiling component = liquid nitrogen (bp -195.8) tends to distill over the first than oxygen (bp 183); repeated liquefaction and distillation give almost 68% pure oxygen o Electrolysis of Water When an electric current is passed through water containing 15% sodium or potassium hydroxide, it is broken down into hydrogen and oxygen which are evolved as gases Oxygen is liberated at the anode, hydrogen gas is liberated at the cathode, iron electrode are separated by an asbestos cloth diaphragm

2.

Oxygen maybe conveniently obtained either thermolysis of KClO3 with MnO2 as catalyst or by the action of water on sodium peroxide 2KClO3 ----> 2KCl + 3O2 2Na2O2 + 2H2O -. 4NaOH + O2 o Colorless, odorless, tasteless gas o Supports combustion more energetically than air does o One volume dissolves in about 32 volumes of water and in about 7 volumes of alcohol at 20C and at pressure 760mm of Mercury o Responsible for oxidative changes in paints, fats and oil o Many materials and some pharmaceuticals contain antioxidants and reducing agent to lessen the effects of oxidation o Commercial oxygen: stored in cylinders, green-colored or carry a green label o Supports rapid combustion = no smoking or open flames nearby and precautions should be taken against ignition by sparks o 99% by volume of O2 and limits the presence of CO2, halogens, acids or alkalis and oxidizing substances o Uses Official category: Inhalant All pathological conditions accompanied by cyanosis and dyspnea are relieved by inhalation of oxygen: /administered by nasal tubes, masks or in tents Pure oxygen should be given only for a limited period of time = two days inhalation can be harmful if the dose is note regulated (edema of the lungs) Given in cases of poisoning by carbon monoxide, coal gas, nitrous oxide, chloroform Carbon Dioxide USP 31 [CO2; 44.01] o Aka Carbonic Acid Gas, Carbonic Anhydride o Odorless, colorless gas o Aqueous solutions are acid to litmus o One liter at 0C and at pressure 760mmHg weighs 1.977g o One volume dissolves in about one volume of water o Supplied in cylinders which are usually gray metallic color o Administered in concentrations up to 7% in oxygen which is stored in gray/green cylinders o Capable of existing in gaseous, liquids or solid states, depending upon the conditions of the temp. or pressure o At 20C it is liquefied by a pressure of about 59 atm o Cooling occurs when the temperature is reduced to about -79C by this process, solid carbon dioxide is formed; dry ice o One advantage: converted directly to a gas, the heat energy required for this conversion being taken from the surrounding in which the solid carbon dioxide is places o Uses Admixture with oxygen and air as a respiratory stimulant for person suffering from impairment of the respiratory

3.

4.

5.

organs in diseases such as pneumonia and in cases of asphyxiation Frozen form, dry ice: treatment of skin conditions: acne, angiomas, corn and calluses, eczema, moles, psoriasis and warts = destroy tissue by freezing it Softdrink industry uses solution of carbon dioxide to make carbonated drinks To displace air in parenteral and topical preparations that are easily oxidized but it must be so stated on the label Helium [He; 4.003] o Colorless, odorless, tasteless gas, not combustible and does not support combustion o Usually supplied in brown cylinders and also as a mixture containing 20% or 40% oxygen in brown/green cylinders o Uses Relatively low density, high diffusibility, a mixture consisting of 80 parts of it with 20 parts of oxygen is used in respiratory diseases, to overcome difficulty in respiration (this mixture only has one third the density of air and since the ease with which the gas can diffuse through a small orifice is related to the density of gas, the 80% helium 20% oxygen mixture penetrates the restricted respiratory passages with greater facility than air does) Has a lower water and fat solubility than nitrogen, helium-oxygen mixture: used in high pressure, underwater diving; reduced the risks of bends Lighter than air = high pitch Nitrous Oxide USP 31 [N2O; 44.01] o Aka Laughing Gas, Nitrogen Monoxide, Dinitrogen Monoxide o Coercible (condensable) gas, colorless, with a slightly agreeable odor and sweetish taste o Quite soluble in water at low temperatures, to which it imparts its odor and taste o Maintains and revives the combustion of many substances because it decomposes easily into its elements o May be distinguished from oxygen using Nitric oxide: oxygen forms reddish brown vapors of NO2 and N2O3 while nitrous oxide will not have any reaction o Produces a form of inebriation when inhaled in small doses = laughing gas o In large doses or mixed with 1 volume of oxygen: reacts as an anesthetic o Uses By inhalation when momentary anesthesia is desired, as by a dentist for the extraction of teeth, opening of the abcesses Nitrogen USP 31 [N2; 28.01] o Aka Azote o Colorless, odorless, tasteless gas o Non-flammable and does not support combustion o Usually sold in black cylinder o Uses Has little therapeutic use

Is official as a pharmaceutical air to displace air, usually to increase the shelf life of an easily oxidized product USP permits use to displace air in parenteral and topical preparations provided it is indicated on the label

Respiratory Stimulants Aromatic Ammonia Spirit is composed of: Ammonium Carbonate NF XV and Strong Ammonia Solution NF XV; both cause a reflex action of the patient taking a sudden deep breath Used to revive an unconscious person 1. Ammonium Carbonate NF 26 o Aka Preston Salt, Sal Volatile, Bakers Ammonia, Ammonium Sesquicarbonate o Consists of proportions of Ammonium Bicarbonate (NH4HCO3) and ammonium carbamate (NH2CO2NH4), yields 40% to 34% ammonia without empyreuma (odor of animal or vegetable matter when charred in a closed vessel) and having a sharp, ammoniacal taste o Solutions are alkaline to litmus o On exposure to air: loses ammonia and carbon dioxide, becoming opaque and is finally converted into friable porous lumps or a white powder of ammonium bicarbonate o Decomposed in hot water o Readily converted in to normal carbonate by dissolving it in dilute ammonia o Also occurs in the preparation of Aromatic Spirit of Ammonia NH4HCO3 + NH3 -> (NH4)2CO3 NH2CO2NH4 + H2O -> (NH4)2CO3 o Decomposition of the salt from its original hard, translucent state to that of a white powder is caused entirely by loss of ammonia and carbon dioxide from the ammonium carbonate, leaving the white powder, ammonium bicarb o Uses Basis of smelling salts, so valuable in hysterical syncope Occasionally used a leavening agent = Bakers Ammonia Official Category: Source of Ammonia 2. Aromatic Ammonia Spirit USP XX o In each 100mL, 1.7g to 2.1g of total ammonia and ammonium carbonate corresponding to 3.5g to 4.5g of (NH4)2CO3 o Volatile oils and as a solvent, ethyl alcohol o Use of translucent pieces of ammonium carbonate to be dissolved in a diluted ammonia solution, generating normal ammonium carbonate o Using additional ammonia solution + decomposed Ammonium Carbonate NF XV, a preparation meeting the analytical standards of the official spirit can be made o Uses Respiratory stimulant by inhaling the vapors Expectorants and Emetics Expectorants: used orally to stimulate the flow of respiratory tract secretions Rationale: this facilitated flow will allow ciliary motion and coughing to move the loosened material toward the pharynx more easily

Used in the treatment of respiratory disorders in which secretions are purulent, viscid or excessive Agents commonly used: terpinhydrate, which may have a direct effect on the bronchial secretory cells and ammonium chloride, glyceryl guaiacolate, syrup of ipecac, potassium iodide and hydroiodic acid syrup (all believed to act with reflex action by irritating the gastric mucosa = stimulating respiratory tract secretion Emetcs: (low doses) been used in cough preparations Rationale: mild emetic response stimulates flow of respiratory tract secretions 1. Ammonium Chloride [NH4Cl; 53.49] o Aka Sal Ammoniac, Salmiac, Ammonium Muriate o Colorless crystals or as a white, fine or coarse crystalline powder, which has a cool, saline taste and is somewhat hygroscopic o Uses Ammonium ion marked increases the secretions, especially the saliva, mucous and sweat = ammonium chloride is valued as an expectorant not only because of the increased amount but it is rendered less viscous and less tenacious Crude form of Sal Ammoniac is used in solution an electrolyte for voltaic batteries Official category: systemic acidifier and chloride replenisher 2. Potassium Iodide USP 31 [KI; 166.01] o Aka Kalium Jodatum o Saturated solution prepared by dissolving 1000g of the salt in 680 mL of hot purified water, cooled to room temp. and diluted to exactly one liter o Cubicle crystals, either transparent or as a white granular powder o Slightly hygroscopic and its solutions are neutral or alkaline to litmus o Uses Official as an expectorant, employed in the treatment of asthma, bronchitis, emphysema and sinusitis Also used as an antifungal agent and antitussive agent Valuable in the treatment of goiter and to avoid the latter Antidotes Agent that counteracts a poison Mechanism Physiological antidote: by counteracting the effects of a posion by producing other effects; ex. Sodium nitrite which converts hemoglobin into methemoglobin in order to bin cyanide Chemical antidote: by changing the chemical nature of a poison; ex. Sodium thiosulfate which causes the conversion of toxic cyanide to non-toxic thiocyanate Mechanical antidote: by preventing the adsorption of the poison into the body; ex. Activated charcoal and kaolin which adsorb the poison; magnesium sulfate and cupric sulfate which inactive and precipitate the toxic material as insoluble salts 1. Sodium Nitrite USP 31 [NaNO2; 69] o Aka Natrium, Nitrosum

White to slightly yellow granular powder or white opaque, fused masses or sticks o Mild saline taste and is deliquescent in air o Solutions are alkaline to litmus o Uses Official category: antidote to cyanide poisoning (2% solution, intravenously) 2. Sodium Thiosulfate [Na2S2O35H2O; 248] o Aka Antichlor Hypo o Large, colorless crystals or as a course, crystalline pwder o Deliquescent in moist air and effloresce in dry air at temp. above 33C o Uses Official category: antidote for cyanide poisoning and iodine poisoning hypo is used for photography As a fixer in photographic films because of its solubilizing action on silver halides Antichlor in bleaching paper pulps 3. Activated Charcoal USP 26 o Aka Carbon Ligni o Residue from the destructive distillation of various organic materials, treated to increase its adsorptive power o Obtained by combustion of wood out of contact of air, residue left being composed of almost pure carbon o Product may have variable adsorptive powers and in many instances almost devoid of such characteristics o Usually inactivated by heating 500C to 900C in the presence of steam o Process is known as activation = removes those substances previously adsorbed and most probably reduces the bigger particles into smaller particles having greater surface area o 1mL of finely divided activated charcoal has a total surface area of about 1000 sq. mt. o Should be preserved in well closed containers o Fine, black, odorless powder, free from gritty matter o Uses Official category: general purpose antidote 4. Cupric Sulfate USP 31 [CuSO45H2O; 249.68] o Aka Blue Vitriol, Blue Stone, Copper Sulfate, Caparrosa Azul, Piedra Lipis o Deep blue, triclinic crystals or as blue crystalline granules or powder o Has a nauseous, metallic taste, effloresces slowly in dry air o Solutions are acid to litmus o Uses Official category: antidote for phosphorous poisoning Used as emetic in doses 300mg Astringent on tonic: 10mg-30mg Tableting Aids Diluents: filler materials which bring tablets up to acceptable size; without them, tablets would be too small for convenience; inert Ex. Lactose; inorganic agents: calcium sulfate, colloidal silicon dioxide o

Calcium Sulfate NF 26 [CaSO4; 136.14] o Aka Gypsum, Alabaster, Satin Spar, Light Spar for the dehydrate calcium sulfate o Anhydrous or contains two moles of water of hydration (CaSO42H2O) o Fine to slightly yellow-white, odorless powder o Anhydrous form: marketed as Drierite, used as a rechargeable laboratory and industrial desiccant o Anhydrous and dehydrate forms are used extensively as a tablet diluent o The hemihydrate of calcium sulfate (CaSO41/2H2O) Plaster of Paris is widely used for making supportive casts by physicians and dental impressions by dentists 2. Collloidal Silicin Dioxide NF 26 (SiO2; 60.08) o Submicroscopic fused silica o Prepared by the vapor-phase hydrolysis of a silicon tetrachlorite (SiCl4) at 1100C o Light, white, non-gritty powder of extremely fine particle size o Uses Tablet diluent. Suspending and thickening agent Lubricants Heat is generated and the tablet can be tightly held in mold of the tableting machine making the ejection very difficult during compression of the granulated mixture into a tablet = lubricants are added to the mixture = possible to eject, no residue Most are insoluble soaps heavy metals of fatty acids Calcium Stearate and Magnesium Stearate Suspending Agents Act by altering the surface character of the solvent (surfactants) and others are thickening agents 1. Bentonite NF 26 [Al2O34SiO2H2O] o Aka Soap Clay, Mineral Soap, Wilkinite o Native, colloidal, hydrated aluminum silicate o Very fine, odorless, pale buff or cream colored powder, free from grittiness o Lightly earthly taste and is hygroscopic o Swells 12 times its volume when added to water = form highly viscous suspensions or gels o Uses Official use: suspending agent Stabilizer in many industrial emulsions Exerts detergent effects, being used in soaps and cleansers Clarifying agent with marked adsorptive powers for dyes and other coloring matter

1.

Chapter IX: Radiopharmaceuticals and Contrast Media Electronically neutral atom: number of electron is
equal to number of protons Different forms of an elements that vary in number of neutrons contained in the nuclei: isotopes When radioactive isotopes decay, they emit certain particles or quantities of energy that are characteristics of the particular isotope involved Major particles of decay o Alpha Particles (,4He2+): Radiations are far the heaviest and slowest of all radioactive emissions Helium nucleus (two protons + two neutrons, at. Mass of 4 and atomic number of 2)

Move at relatively slow speed, 0.1 the speed of light Penetrating power is very low and can be stopped by a piece of paper or a very thin sheet of aluminum Usually emitted only from elements having atomic numbers greater than 82 Isotopes emitting alpha particles will decay to element having a mass number of 4 or less and atomic number os 2 or less than the original isoptope 226Ra -> 222Rn + 4He2+ o Beta Particles (-) Negatively charged species having a mass of an electron Move at a faster velocity often approaching 0.9 the speed of light Emissions from elements do not alter the mass number but alter the atomic number Have more penetrating power and able to travel 10cm-15cm in water and penetrate almost 1-inch thickness of aluminum Sometimes called negatrons Emitted by unstable nuclei having neutrons in excess of protons If neutron/proton ratio exceeds stable limits: transformation of a neutron to a proton will occur, with expulsion of beta radiation Element undergoing this type of transformation will decay to the element having the next highest atomic number 1n -> 1p + 14C -> 14N + Positron (+) Identical to the electron with the exception of having a positive charge Emitted from nuclei having a proton/neutron ratio above stable limits Proton is transformed into a neutron, accompanied by emission of a positron Elements emitting positron radiation will decay to the element having the lowest atomic number 1p -> 1n + + 65Zn -> 65Cu + + Gamma Radiation () Photon of electromagnetic radiation Demonstrates both wave and particle properties as do electrons and beta particles Ray are short wavelength similar to xrays and travel at a speed of light No mass and no charge, very high energy giving them excellent penetrating power Very thick lead is requires to protect against radiation from strong gamma emitting sources Emission from an element results in lowering of the nuclear energy level of the element but no elemental

change is noted unless one of the other type of radiation is also emitted Emission is almost always accompanied by the emission of other forms of radiation If gamma does occur alone, it will involve the transition of metastable state of an isotope either to a stable form or to a form of the same isotope which will continue to decay by other means 59Co (n, ) -> 60mCo -> 60mCo + -> 60Ni + + + 2 Type of radiation similar to gamma rays is seen in the emission of x-rays through a process known as Kcapture ^ produced by isotope with an unstable proton/neutron ratio but with insufficient energy to emit with a positron; nucleus capture an electron from the so called K shell (1s orbital) which combines with a proton to form a neutron ^rearrangement of the orbital electrons takes place with the release of energy in the form of x-rays ^energy released comes largely from the necessary electronic rearrangements ^loss of a proton in the nucleus indicates that the isotope will decay to the element having the next lowest atomic number 197Hg ---------> 197 Au + x-rays Biological Effects of Radiation Effect of radioactive particles impinging upon biological tissues depends upon Number of factors related to the ability of the radiation to penetrate tissue Energy of radiation Particular tissue Surface area exposed Dose rate of the radiation Destructive aspect of radioactivity is directly related to its interaction with molecules present in the tissue to form abnormal amounts of ion and/or free radicals These chemical species can alter the local pH or serve to initiate free radical chain reactions, resulting in the production of peroxides or other toxic compounds These can create a hostile environment for tissue cells = necrosis and complete destruction of the tissue or organ Internal Administration of Radioisotopes Radiopharmaceuticals: preparation containing isotopes which are used internally for therapeutic and diagnostic purposes Isotopes important as radiopharmaceuticals are Those emitting beta and gamma radiation since they cant penetrate body tissues Those that can be concentrated in specific manner in certain organ/cells; ex. 131I in thyroid tissue Those which should be eliminated from the body easily and aside from the associated radioactivity, they and the decay products should be of low toxicity

Radiopharmaceutical Preparations 1. Sodium Chromate Cr 51 Injection (Chromitope Sodium Rachromate -51) o Uses: diagnostic determination of RBC mass, volume and survival time, and scanning of spleen 2. Gold Au 198 Injection (Aurcoloid -198, Aureotope, Auroscan) o Uses: diagnostic preparation for scintillation scanning of the liver 3. Sodium Iodide 123 Solution (Iodotope I 125), Sodium Iodide I 131 Capsules and Solution (Iodope I-131) o Uses: diagnostic aid in the study of the function of the thyroid gland, for scanning thyroid gland; for I-131: to determine the blood and plasma volumes and determination of cardiac output 4. Sodium Rose Bengal I-131 Injection (Robengatope I131) o Uses: radioactive tracer in the determination of the liver function 5. Sodium Iodohippurate I-131 Injection (Hippuran I-131) o Uses: diagnostic agent to determine kidney function 6. Chlormerodin Hg 197 Injection and Hg 203 Injection o Uses: Scintillation scanning of the kidneys and brain 7. Sodium Phosphate P 32 Solution (Phosphotope) o Uses: treatment of polycythemia vera (increase in RBC), localization of intraocular tumors 8. Technetium Tc 99m Injection (Sodium Pertechnetate) o Uses: Brain scanning to determine the presence and location of neoplastic lesions 9. Cyanocobalamin Co-57 and Co-60 Capsules and Solutions o Use: Diagnostic agent for pernicious anemia Radiopaque Contrast Media Chemical compounds containing elements of high atomic number which will stop the passage of x-rays 1. Barium Sulfate USP 31 [BaSO4; 233.40] o Aka Barium Meal, Sulfato de Bario, Esophotrast o Caution: in preserving, the title should always be written in full, to avoid confusion with the poisonous barium sulfide and barium sulfite o Fine, white, odorless and bulky powder, free from grittiness o Uses Mainly and widely used in medicine as an opaque contrast medium in the roentgenographic examination of the intestinal tract and the stomach so that they maybe photographed