Inorganic Pharmaceutical Chemistry Study Guide: Sclerosing Agents, Expectorants, Sedatives, and Antidotes

Sclerosing Agents

• Definition: Sclerosing agents are certain injections which are used to irritate and damage the wall of a vein, resulting in its occlusion (closing).

• Application: This procedure is primarily done in cases of varicose veins. In these veins, the circulation is relatively slow, allowing the injection to remain undiluted for a longer period.

• Common Examples:

  • Hypertonic saline (more important than others).

  • Sodium morrhuate.

  • Quinine hydrochloride.

  • Ethanolamine oleate.

Sodium Chloride Hypertonic Injection (Hypertonic Saline)

• Description: This is a sterile, hypertonic solution of sodium chloride in water for injection.

• Composition: It contains $1\% - 60\% \, w/v$ of Sodium chloride ($NaCl$) and $270 \, millimoles$ each of Sodium and Chloride ions per litre.

• Preparation Methods:

  • From Sea Water: Sea water contains approximately $3\%$ sodium chloride along with other substances. At high tide, sea water is allowed to flow into shallow ponds where insoluble minerals and suspended matters precipitate out. The liquid then moves to crystallizing ponds for evaporation. More soluble salts like Magnesium sulphate ($MgSO_4$) and Barium iodide ($BaI_2$) are removed. Calcium and Magnesium salts are eliminated by treating the brine with soda ash (commercial anhydrous sodium carbonate) and lime, or soda ash and caustic soda ($NaOH$). The purified brine is then concentrated in triple effect evaporators.

  • From Underground Rock-Salt Deposits: Holes are drilled into rock-salt beds and water is pumped down. The resulting salt solution (brine) is pumped to the surface and evaporated in triple effect evaporators. A special lime-soda process is used for purification.

  • Analytical Grade (Purest Form): Obtained by passing hydrogen chloride gas ($HCl$) into a saturated salt solution. Very pure sodium chloride precipitates out, and the crystals are centrifuged and dried.

• Properties:

  • Appears as colorless, transparent cubes or white crystalline powder.

  • Odourless with a saline taste.

  • Slightly hygroscopic (often due to traces of magnesium or calcium chloride).

  • Freely soluble in water and slightly soluble in alcohol.

• Chemical Reactions:

  • Reaction with silver nitrate: $NaCl + AgNO_3 \rightarrow AgCl \downarrow + NaNO_3$. The white precipitate ($AgCl$) is photosensitive, soluble in dilute ammonia, and insoluble in nitric acid.

  • Reaction with acids: $2NaCl + H_2SO_4 \rightarrow 2HCl + Na_2SO_4$.

  • Oxidation: Easily oxidized to liberate chlorine. Heating with manganese dioxide ($MnO_2$) and concentrated sulphuric acid produces chlorine: $2NaCl + MnO_2 + 2H_2SO_4 \rightarrow MnSO_4 + Na_2SO_4 + 2H_2O + Cl_2$.

• Tests for Purity:

  • pH: $5$ to $7.5$.

  • Bacterial Endotoxins: Not more than $0.5 \, endotoxin \, units/ml$.

  • Heavy Metals: Evaporate a specific quantity, add dilute acetic acid, and dilute with water. Complies with Method A for heavy metals limit tests.

• Storage: Store in single-dose containers of glass or plastic. Note: Small solid particles may separate from glass containers over time.

• Uses:

  • Fluid and electrolyte replenisher.

  • Used intravenously very slowly during severe electrolyte imbalance.

  • Specific use as a sclerosing agent for varicose veins.

Sodium Tetradecyl Sulphate

• Preparation: Prepared by sulphating tetradecyl alcohol ($C_{14}H_{29}OH$) and converting it into its sodium salt.

• Properties: Available as a concentrate, which is a clear, colorless aqueous gel.

• Identification:

  • Gas chromatography test.

  • Methylene blue test: Adding dilute sulphuric acid and chloroform to an aqueous solution and shaking. The chloroform layer becomes intensely blue.

  • Hydrolysis: Hydrolysed in hot ethanol with dilute $HCl$. Adding barium chloride to the filtrate produces a white crystalline precipitate.

  • Gives reactions characteristic of sodium salts.

• Purity Tests: Includes tests for unsulphated matter (extracted with n-pentane and dried at $105 \, ^\circ C$), alkalinity, chloride, sulphate, and sulphated ash.

• Official Preparations: Sodium tetradecyl sulphate I.P. and U.S.P.

Expectorants

• Definition: Drugs that enhance the secretion of fluids from the respiratory passages, making it easier to remove phlegm (sputum) through coughing.

• Mechanism of Action:

  • Increasing bronchial secretion.

  • Reducing viscosity (mucolytic agents).

• Classification:

  1. Sedative (Reflex) Expectorants: Stimulate gastric reflexes to produce expectoration. Known as stomach irritant expectorants. Examples: $NH_4Cl$, $KI$, Antimony potassium tartrate, Sodium citrate, and herbs like Ipecac.

  2. Stimulant Expectorants: Cause direct or indirect stimulation of respiratory secretory cells. They increase secretions and decrease sputum viscosity. Examples: Anise oil, Eucalyptus oil, Lemon oil, and Terpin hydrate.

Potassium Iodide ($KI$)

• Preparation: Prepared by adding a slight excess of iodine to a potassium hydroxide solution to form potassium iodide and iodate. The iodate is then reduced to iodide by heating with charcoal.

  • $6KOH + 3I_2 \rightarrow KIO_3 + 5KI + 3H_2O$

  • $KIO_3 + 3C \rightarrow KI + 3CO \uparrow$

• Properties:

  • Large transparent colorless or white opaque cubes, or white granular powder.

  • Saline and slightly bitter taste.

  • Stable in dry air but slightly deliquescent in moist air.

  • Very soluble in water and soluble in alcohol.

  • Aqueous solutions can dissolve iodine to form $KI_3$: $KI + I_2 \rightleftharpoons KI_3$.

• Purity Tests:

  • Arsenic: Limit test using stannated hydrochloric acid.

  • Barium: No turbidity should develop upon adding dilute sulphuric acid.

  • Iodate: Adding dilute sulphuric acid and starch solution should produce no blue color (iodates react with iodide in acid to liberate free iodine).

• Uses:

  • Source of iodine for thyroid deficiency (e.g., in iodized salt).

  • Expectorant and saline diuretic.

  • Mild antifungal activity.

  • Laboratory reagent (e.g., Mayer’s reagent, Nessler’s reagent) and reducing agent.

Sedatives and Anticonvulsants

• Sedative Definition: A substance that causes mild depression of the Central Nervous System (CNS), resulting in a calming effect. Higher doses may produce sleep (hypnotics).

• Potassium Bromide ($KBr$):

  • Historical context: Bromides were once widely used for fits and epilepsy but have been largely replaced by less toxic synthetic organic anticonvulsants due to the risk of "bromism" (chronic bromide toxicity/accumulation).

  • Preparation:

    1. Action of potassium hydroxide on bromine followed by reduction of the resulting bromate with charcoal: $6KOH + 3Br_2 \rightarrow KBrO_3 + 5KBr + 3H_2O$; $KBrO_3 + 3C \rightarrow KBr + 3CO \uparrow$.

    2. Reaction of iron turnings with bromine to form ferrous-ferric bromide, which is then boiled with potassium carbonate: $3Fe + 4Br_2 \rightarrow Fe_3Br_8$; $Fe_3Br_8 + 4K_2CO_3 \rightarrow 8KBr + 4CO_2 \uparrow + Fe_3O_4 \downarrow$.

  • Properties: Colorless transparent or white cubical crystals. Sharp, saline, bitter taste. Soluble in water ($1 \, in \, 1.6$). Crackles (decrepitates) when heated and fuses at approximately $730 \, ^\circ C$ without decomposition.

  • Purity Tests:

    • Bromate: Adding dilute $H_2SO_4$ and chloroform. The chloroform layer must remain colorless.

    • Iodide: Adding ferric chloride and heating; the chloroform layer must not turn yellow or violet.

    • Sodium: Tested using potassium antimonate; no precipitate should form within $15 \, minutes$.

  • Side Effects: Cumulative toxicity leads to CNS depression and skin rashes (bromism).

Respiratory Stimulants

• Definition: Agents used to revive fainted patients by causing a reflex deep breath through CNS stimulation via inhalation. Often called "smelling salts."

• Ammonium Carbonate:

  • Synonyms: Sal volatile, Preston's salt, Hartshorn, Ammonium sesquicarbonate.

  • Composition: A mixture of ammonium bicarbonate ($NH_4HCO_3$) and ammonium carbamate ($NH_2COONH_4$).

  • Preparation: Subliming a mixture of ammonium sulphate or chloride with chalk (Calcium carbonate) in iron retorts: $2(NH_4)_2SO_4 + 2CaCO_3 \rightarrow NH_4HCO_3 \cdot NH_2COONH_4 + NH_3 + H_2O + 2CaSO_4$.

  • Properties: White powder or translucent masses with a strong ammonia odor. Alkaline to litmus. On exposure to air, it loses $NH_3$ and $CO_2$, becoming opaque and converting into ammonium bicarbonate.

  • Decomposition: Decompounds in hot water. Reacts with mineral acids: $NH_4HCO_3 \cdot NH_2COONH_4 + 3HCl \rightarrow 3NH_4Cl + H_2O + 2CO_2 \uparrow$.

Antidotes

• Definition: An agent that counteracts a poison.

• Mechanisms:

  1. Physiological: Counteracts poison effects by producing opposite physiological effects (e.g., Sodium nitrite for cyanide).

  2. Chemical: Changes the chemical nature of the poison (e.g., Sodium thiosulfate converts cyanide to thiocyanate).

  3. Mechanical: Prevents absorption (e.g., Activated Charcoal via adsorption).

• Cyanide Poisoning Treatment:

  • Mechanism: Cyanide binds to the ferric ($Fe^{3+}$) ion of cytochrome oxidase, stopping cellular respiration.

  • Sodium Nitrite ($NaNO_2$): Oxidizes haemoglobin (ferrous, $Fe^{2+}$) to methaemoglobin (ferric, $Fe^{3+}$). Methaemoglobin binds cyanide before it enters cells.

  • Sodium Thiosulfate ($Na_2S_2O_3$): Reacts with cyanide (catalyzed by the enzyme rhodanese) to form non-toxic thiocyanate ($SCN^-$), which is excreted: $Na_2S_2O_3 + CN^- \rightarrow SCN^- + Na_2SO_3$.

• Sodium Nitrite ($NaNO_2$):

  • Preparation: Reducing sodium nitrate ($NaNO_3$) using carbon/lime, lead at $450 \, ^\circ C$ to $500 \, ^\circ C$, or sulphur/sodium hydroxide.

  • Properties: White/slightly yellow granular powder. Deliquescent. Behaves as both an oxidizing agent (liberates iodine from $KI$) and a reducing agent (decolors $KMnO_4$).

  • Assay: Back titration of excess $KMnO_4$ with decinormal oxalic acid.

  • Warnings: Can form carcinogenic nitrosamines in the intestinal tract.

• Sodium Thiosulfate ($Na_2S_2O_3 \cdot 5H_2O$):

  • Preparation: Boiling sodium sulphite solution with flowers of sulphur: $Na_2SO_3 + S \rightarrow Na_2S_2O_3$.

  • Properties: Monoclinic crystals. Deliquescent in moist air, efflorescent in dry air above $23 \, ^\circ C$.

  • Reaction with Silver Nitrate: Forms white precipitate that turns yellow, brown, and finally black ($Ag_2S$).

  • Assay: Direct titration with iodine using starch indicator: $I_2 + 2Na_2S_2O_3 \rightarrow 2NaI + Na_2S_4O_6$ (sodium tetrathionate).

• Activated Charcoal:

  • Preparation: Destructive distillation of organic matter (wood, coal) followed by activation with high-temperature steam or chemicals ($ZnCl_2$, phosphoric acid) to increase surface area/adsorptive power.

  • Identification: Burns slowly without flame when heated to redness.

  • Adsorbing Power: Must adsorb not less than $40\%$ of its weight of phenazone. Tested via titration with potassium bromate using methyl red indicator.