EXPECTORANTS & EMETICS INTRODUCTION Cough, a protective reflux (both voluntary and involuntary) helps to expel irritant matter from the respiratory tract. When a person coughs there is a short intake of breath and the larynx closes momentarily. It is a vital part of the defence mechanism. It can be caused by infections, chemical irritants, asthma, lung tumour, breathing in dust particles. It is two types : 1) Productive Cough : A productive cough produces a phlegm or mucus (sputum). The mucus may have drained down the back of throat from the nose or from the lungs. A protective cough should not be supressed. It clears mucus from the lungs. 2) Irritative or Non-productive cough : A non-productive cough does not produce sputum. A dry, hacking cough may develop towards the end of a cold or after exposure to an irritant such as dust and smoke. The latin word 'Expectorate' means 'to drive from the chest'. Expectorants are drug used to help in the removal i.e. explusion of secretions or exudate from the trachea, bronchii or lungs. Hence, they are used in the treatment of cough. They act upon the respiratory tract in two ways : i) By decreasing the viscosity of the bronchial secretion and facilitating their elimination, local irritants are expelled and ineffectual coughing is required. ii) By increasing the amount of respiratory tract fluid, a demulcent action is exerted on dry mucosal lining & relieving the unproductive cough. Inorganic saline expectorants are :- Ammonium salts (Ammonium Chloride), iodide (Potassium/Sodium Iodide), citrates and Antimony Potassium Citrate. Classification of Expectorants • Classification of expectorants is according to their mechanism of action (i) sedative type and (ii) stimulant type. Sedative expectorants: These are stomach irritant expectorants which are able to produce their effect through stimulation of gastric reflexes. • Examples of sedative expectorants include bitter drugs such as ipecac, senega, Indian squill, and compounds such as antimony potassium tartrate, potassium iodide, etc. ammonium chloride, sodium citrate, Stimulant expectorants: These are the expectorants which bring about a stimulation of the secretory cells of the respiratory tract directly or indirectly. • Since these drugs stimulate secretion, more fluid gets produced in respiratory tract and sputum is diluted. • Examples of stimulant expectorants include drugs such as Eucalyptus, lemon. EMETICS An emetic is a drug that produces vomiting. Vomiting is the involuntary, forceful expulsion of the content of one's stomach and sometimes the nose. • The emetics act either by - local irritation of gastric mucosa (ammonium bicarbonate, ipecacuanha) - directly on the chemoreceptor trigger zone in the floor of IV ventricle in medulla (i.e., centrally acting emetics). It is used medically where a substance has been ingested and must be expelled from the body immediately. Gastric secretions and likewise, vomiting are highly acidic. Salt water and mustard water have been used since ancient times as emetic. Hydrogen peroxide is used as an emetic in verterniary practise. Inorganic compounds e.g. Copper sulphate, Sodium chloride, Zinc sulphate and Potassium antimony tartrate belong to the latter type. Emetics should be avoided in children and in the elderly pregnant women and in patients suffering from CNS depression, unconscious or in coma. If the vomiting reflex continues for an extended period, dehydration, hypokalaemia and alkalosis may occur and replacement of fluid and electrolytes may be necessary. Emetics are also sometimes used in the preparation of cough syrups. • Emetics are sometime added to cough preparations in low doses to stimulate flow of respiratory tract secretions. • There are types of poisoning in which poisons may remain in stomach for sometime before entering intestine where they may get absorbed. • Before this occurs, emetics are given to patients for physically expelling the toxic substances and reduce the harmful effects and may be able to save a patient's life. • When a patient is in unconscious state, emetics may not be very useful and gastric lavage may be required. AMMONIUM CHLORIDE Chemical Formula : NH4CI Molecular Weight : 53.49g/mol Synonyms : Ammonium Muriate, Sal Ammoniac, Salmiac, Amchlor, Ammon. Chlor. Ammonium chloride occurs naturally in volcani regions, forming on volcanic rocks near fume releasing vents. Method of Preparation: It is a product of the Solvay Process used to produce Ammonium Chloride and Sodium Carbonate CO2 + 2NH3 + 2NaCl + H2O 2NH2C1 + Na2CO3 This method is used to minimize ammonia release in some industrial operations. Ammonium chloride is prepared by combining ammonia with either hydrogen chloride (gas) or hydrochloric acid. NH3 + HCI NH4Cl Properties: It is a white crystalline salt, highly soluble in water. Solutions of ammonium chloride are mildly acidic. It is somewhat hygroscopic. It is odourless and possesses cooling saline taste. On heating, it sublimes without melting. Ammonium chloride reacts with a strong base e.g. sodium hydroxide to release ammonia gas NH4Cl + NaOH → NH3 + NaCl + H2O Ammonium chloride also reacts with alkali metal carbonates at elevated temperatures, giving ammonia and alkali metal chloride. 2NH4Cl + Na2CO3 → 2NaCl + CO2 + H2O + 2NH3 Assay: Dissolve 1.0g of ammonium chloride in 2o ml of distilled watr. Add a mixure of 5 ml formaldehyde solution which is previously neutralize with 0.1M NaOH and 20 ml distilled water. Leave it for 2 minutes and titrate with 1M sodium hydroxide using phenolphthalein as indicator. Storage: It should be stored in tightly closed containers because it is hygroscopic. Uses Ammonium chloride is a nitrogen source in fertilizers e.g. chloro ammonium phosphate. It is used as an expectorant in cough medicine. Its expectorant action is caused by irritative action on the bronchial mucosa. Ammonium chloride is used as a systemic acidifying agent in treatment of severe metabolic alkalosis. It is also used as flavouring agent. Antimony Potassium Tartrate Molecular formula: C4H4 K07Sb Synonyms: Potassiumm Antimonyl Tartrate or Emetic Tartar, Tartraised Antimony. It is double salt of potassium and antimony of tartratic acid. Properties: It occurs as odourless, colourless, transparent crystals or white powder. The crystals effeverscenes on exposure to air and do not readily rehydrate even when exposed to high humidity. It is soluble in water and glycerol; insoluble in alcohol. Solutions in water are acidic to litmus. Prepration: It is prepared by mixing antimony trioxide Sb 2O3 (5 parts) with potassium acid tartrate (6parts) in a fine paste and left aside for a day. It is then boiled with water for fifteen minutes while stirring. The liquid is then filtered hot and the filtrate left for crystallization. The crystals are collected on the filter and dried. Assay : The assay is based upon the oxidation-reduction reaction. Iodine solution is used as an oxidising agent, which converts antimony to antimonic state (Sb2O5). Dissolve about 500mg of Antimony potassium tartrate, accurately weighed , in 50 mL of water, add 5g of sodium tartrate, 2g of sodium borate and 3mL of starch Test solution (TS) and immediately titrate with 0.1N iodine VS to the production of blue colour. Each Ml of 0.01 iodine is equivalent to 16.70mg of C8H4K2O12Sb2.3H2O. Strong alkalies like sodium hydroxide or sodium carbonate is not used, as it would react with iodine to form hypoiodate. 2NaOH + I2 → NaOI + NaI+ H2O 2C4H4O7SbK + 3H2O + 2I2 → 2KHC4H4O6+ Sb2O3+ 4HI Antimony sodium tartrate also acts similarly as emetic agent. Uses: Antimony potassium tartarte is used initially as an emetic. It is also used in the treatment of Schistosomiasis and Leishmaniasis. It is given by intervenous injection or should never be given by intramuscular or subcutaneous injection because it causes severe pain and necrosis. Storage: It is stored in tightly closed containers. POTASSIUM IODIDE Chemical Formula: KI Molecular Weight :- 166.01 g/mol Synonyms: Kalii Iodidum, Potassium Iodide. Method of Preparation: It is prepared by treating iron filling with iodine under water to get iodide which is then reacted with potassium carbonate. K2CO3 + FeI2 2KI + Fe2CO3 Hydroiodic acid when treated with potassium bicarbonate results in the formation of potassium iodide. KHCO3 + HI KI + H2CO3 Properties: It occurs as odourless, transparent or opaque crystals. It is white granular powder. It is slightly hygroscopic, taste is saline and slightly bitter. It is very soluble in water and even more so in boiling water, freely soluble in glycerine and soluble in alcohol. On long exposure to air it becomes yellow due to liberation of iodine and small quantity of iodate may be formed. lodine readily dissolves in an aqueous solution of potassium iodide, forming a dark brown solution which contains potassium iodide. KI + I2 Kl3 Assay : Dissolve 500 mg of Potassium iodide, accurately weighed , in about 10mL of water and add 35 ml of hydrochloric acid. Titrate with 0.05M potassium idodate VS until the dark brown solution which is produced becomes pale brown. Storage: It is stored in well closed containers. Uses: It is used as an ingredient of expectorant mixture. It may be used for the prophylaxis and treatment of simple goitre. It is used as an antifungal agent in veterinary practise. Potassium iodide solution is used as iodine supplement. COPPER SULPHATE Molecular Formula: CuSO4.5H20 Synonym: Blue vitriol Molecular Weight: 159.6 g/mol Preparation: It is prepared by dissolving cupric oxide (or) cupric hydroxide (or) cupric carbonate in dilute H2SO4 CuO + H2SO4, → CuSO4 + H2O Cu(OH)2 + H2SO4 → CuSO4 + 2H2O CuCO3 +H2SO4 → CuSO4 + H2O + CO2 Properties: Its hydrated salt is blue in colour but anhydrous salt is colourless. It readily dissolves in water but is insoluble in alcohol. Uses: It is used as a germicide and insecticide in agriculture. A mixture of copper sulphate and lime, commonly known as Bordeaux mixture, is used as fungicide. Assay: Weigh accurately 1 gm of copper sulphate (CuSO4) in 50 ml of water, add 3 gm of potassium iodide, 5 ml of acetic acid and titrate the liberated iodine with 0.1 N Sodium thiosulfate (Na2S2O3) using solution of starch as indicator. Respiratory stimulants Respiratory stimulants belong to the class known as Central Nervous System Stimulants. Drugs which increase the activities of various functions of the CNS are called as central nervous system stimulants or stimulants or analeptics. One of the important features of stimulant activity is respiratory stimulation'. This action is brought through stimulation of chemo-receptors and the vasomotor centres by various agents. Various drugs and chemicals stimulate respiratory function by different mechanisms. The role of gases like carbondioxide, oxygen is discussed under inhalants. The pH or hydrogen ion concentration of blood and various chemicals which alter the pH also affect respiration. (This is Mainly through chemo-receptors). Inorganic compounds act as respiratory stimulant by reflex mechanism. The epithelial cells of trachea, bronchial and bronchiolae get stimulanted by irritation by drugs. This in turn leads to respiratory stimulation. Ammonical salts and preparation are in general considered as respiratory stimulants because they give of ammonia gas which irritates respiratory tract and acts as reflex stimulant. Some important and useful compounds are covered below. Ammonium Carbonate : This compound is discussed under expectorant category. The compound is a mixture of ammonium bicarbonate and ammonium carbonate. It is volatile and gives smell of ammonia. The ammonia gas when inhaled stimulatus respiratory center and thus acts as respiratory stimulant. Ammonium Solution Dilute : It contains approximately 10% w/w of NH3 and is prepared by diluting a strong ammonia solution with purified water. Ammonia gas is a reflex stimulant. It acts directly by irritation of the trigeminal nerve. A dilute ammonia solution being alkaline in nature is not used directly. Aromatic Spirit of Ammonia : It contains 1.12-1.25% w/w of free ammonia and 2.76-3.24% w/v of ammonium carbonate Composition : Ammonium bicarbonate Ammonia solution strong 25g 70ml Lemon oil 5.1ml Nutmeg oil 3ml Alcohol (90%) 750 ml Purified water to produce 1000 ml Preparation : Lemon oil, nutmeg oil, alcohol and about 375 ml of water is placed in a distillation assembly and about 875 ml of distillate is collected. In addition, 35 ml of distillate is collected separately and to it ammonium bicarbonate and ammonia is added. The contents are warmed on water-bath at 60°C, stirred, filtered through cotton wool and filtrate added gradually to first distillate. Sufficient water is added to produce the desired volume. Action and Uses : It is supplied in single-dose thin walled glass vials wrapped in cotton envelop. On breaking, the contents are absorbed by cotton and on inhalation respiratory stimulation is produced. Assay: The preparation is analysed for alcohol, ammonium carbonate and for free ammonia content. Ammonium carbonate: Place about 10ml of water in a weighing bottle, tare the bottle and its contents add 2g of the sample and weigh accurately, transfer the content of the bottle to a 250 ml flask and slowly add with mixing 50 ml of 1N Sulfuric acid. When solution has been effected wash down the sides of the flask add methyl orange TS and titrate the solution the excess acid with 1N sodium hydroxide. Each ml of 1N sulphuric acid is equivalent to 17.03mg of NH3 Storage: It should be preserved in well-closed stoppered containers and kept in a cool place.
