Pharmaceutical Inorganic Chemi

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### Unit 1: Syllabus #### Impurities in Pharmaceutical Science - History of Pharmacopoeia - Sources and types of impurities - Principle involved in limit tests for chloride, sulfate, iron, arsenic, lead, and heavy metals. #### Pharmaceutical Inorganic Chemistry - Definition and scope - Inorganic compounds in drug preparation (e.g., NaCl, HCl, Sodium Bicarbonate, Copper Sulphate, Antacids). #### Pharmacopoeia - **Definition:** A book of standards for drugs, dosage forms, and pharmaceutical aids, published under governmental authority. - **Etymology:** From Greek words "pharmakon" (drug) and "poeia" (to make). - Contains formulas, monographs, and detailed drug information. ### Indian Pharmacopoeia - **Definition:** An official document responsible for quality control and assurance of pharmaceutical products in India. - Defines identity, purity, safety, and strength of drugs. - Approved under the Second Schedule of the Drug and Cosmetic Act 1940 and Rules 1945. - Published by the Indian Pharmacopoeia Commission (IPC) on behalf of the Ministry of Health and Family Welfare, Government of India. - IP standards are legally acceptable. #### History and Development - **1833:** First recommended by the East India Company and Bengal Pharmacopoeia. - **1885:** British Pharmacopoeia (BP) made official in India. - **1948:** Indian Pharmacopoeia Committee developed to publish IP. - **1955:** First edition of IP (IP 1955) published by IPC. - Contains monographs with drug lists, sources, tests, formulas, uses, dosages, and storage conditions. - Serves as a reference standard for laboratory, industry, and academic institutions. - Subsequent editions and addendums published. #### Indian Pharmacopoeia Editions | Editions | Year | Addendum or Supplement | No. of Volumes | Monographs | |---------------|------|------------------------|----------------|------------| | 1st edition | 1955 | Supplement 1960 | 2 | 986 | | 2nd edition | 1966 | Supplement 1975 | 3 | 890 | | 3rd edition | 1985 | Addendum 1989, 1991 | 2 | 261 | | 4th edition | 1996 | Addendum 2000, 2002, 2005 | 3 | 1149 | | 5th edition | 2007 | Addendum 2008 | 3 | 271 | | 6th edition | 2010 | Addendum 2012 | 3 | 52 | | 7th edition | 2014 | Addendum 2015, 2016 | 4 | 577 | | 8th edition | 2018 | Addendum 2019 | 4 | 220 | | 9th edition | 2022 | - | - | - | ### Impurities: Sources and Types - **Definition:** Unwanted foreign substances in pharmaceuticals, making them impure and potentially toxic. - Impurities can lower drug quality and cause toxicity. - Pharmaceutical solution + Impurities = Impure (e.g., Lead, Calcium, Arsenic, Iron, Chloride). #### Types of Impurities 1. **Organic Impurities:** - Produced during synthesis or storage of drug substances. - Process and drug-related (from raw materials, by-products, excipients, reagents). - Not easily identified. 2. **Inorganic Impurities:** - Produced during manufacturing processes. - Can be due to reagents, inorganic salts, heavy metals, catalysts. - Easily identified by limit tests. 3. **Residual Solvents:** - Impurities produced during manufacturing from solvents. #### Categorization by Effects - **Destructive Impurities:** - Stop or prohibit the function of substances. - Can be removed by chemical or physical methods (e.g., distillation). - **Constructive Impurities:** - Improve the function of substances. - Example: Adding less than 2% carbon to pure iron to manufacture steel. ### Sources of Impurities - Impurities in drug products can come from: - Manufacturing process - Raw materials - Excipients - Accidentally #### Common Sources 1. **Raw Materials:** Impurities can occur in raw materials, contaminating the end product (e.g., traces of lead, copper, silver). 2. **Reagents Used in Manufacture:** Impurities from reagents if not properly washed, contaminating the final product (e.g., ammoniated mercury precipitate). 3. **Processes During Manufacturing:** - Impurities enter materials during processes. - Due to formulation/excipients. - Due to residue solvent. - Due to chemical processes (e.g., oxidation). 4. **Environment Related:** Impurities from the atmosphere can contaminate final products (e.g., gases like H2S, NH3, humidity). 5. **Defects:** Occur during manufacturing (e.g., improper mixing, pressure, pH). 6. **Manufacturing Hazards:** Contamination during manufacturing (e.g., mixing of dirt, glass, metallic or plastic fragments). 7. **Storage:** Impurities occur during storage (e.g., dust, insects, animals polluting products). 8. **Accidental/Adulteration:** Toxic substances accidentally mixed (e.g., expensive KBr adulterated with cheaper NaBr). ### Effects of Impurities - Even small amounts of impurities can cause toxicity if present in excess. - Can alter physical and chemical properties. - May make the substance therapeutically inactive. - Can reduce the shelf-life of a substance. - May change color, odor, taste, making the substance unhygienic and unfit for use. ### Limit Tests - **Definition:** Quantitative or semi-quantitative tests to identify and control small quantities of impurities. - Used for determination of impurity amounts (e.g., limit test for chloride). - **Principle:** Compare turbidity/opalescence of test solution with a standard solution. - If test solution turbidity standard solution turbidity, limit test failed. ### Limit Test for Chloride - **Purpose:** Identifies chloride ion impurities and measures their quantity. - **Principle:** Silver nitrate reacts with soluble chloride to form silver chloride precipitate, insoluble in dilute nitric acid ($$Cl^- + AgNO_3 \xrightarrow{HNO_3} AgCl \downarrow + NO_3^-$$). - **Procedure:** 1. Prepare test and standard solutions. 2. **Apparatus:** Nessler's cylinder, measuring cylinder, glass rod. 3. **Chemicals:** Dilute Nitric acid, Silver Nitrate, NaCl. | Test Solution (Nessler Cylinder - A) | Standard Solution (Nessler Cylinder - B) | |--------------------------------------|------------------------------------------| | Specified substance (1g) | 1mL of 0.05845% w/v NaCl solution | | + 10mL water | + 1mL Nitric acid | | + 1mL Nitric acid | | 4. Dilute both to 50mL in Nessler Cylinders. 5. Add 1mL Silver Nitrate to both. 6. Set aside for 5 minutes. 7. Compare turbidity. - **Result:** - If test solution turbidity standard solution turbidity, sample fails and needs impurity control. - **Why dilute HNO3?** Makes the solution acidic, dissolving other impurities except chloride, which is insoluble in HNO3 and causes turbidity. ### Limit Test for Sulphate - **Purpose:** Controls and identifies sulphate impurity. - **Principle:** Barium chloride reacts with soluble sulphate in the presence of dilute HCl to form barium sulphate precipitate, generating turbidity ( $$SO_4^{2-} + BaCl_2 \xrightarrow{HCl} BaSO_4 \downarrow + 2HCl$$ ). Turbidity is compared with a standard solution. - **Role of Barium Chloride:** Present in barium sulphate reagents, containing barium chloride, sulphate-free alcohol, and potassium sulphate, which increases the sensitivity of the test by preventing supersaturation. - **Procedure:** 1. Prepare test and standard solutions. | Test Solution (Nessler Cylinder - A) | Standard Solution (Nessler Cylinder - B) | |--------------------------------------|------------------------------------------| | 1g specified substance of sulphate | 1mL of 0.1089% w/v K2SO4 solution | | + 2mL HCl | + 2mL HCl | | Added in 45mL water | Added in 45mL distilled water | | + 5mL Barium Sulphate Reagent | + 5mL Barium Sulphate Reagent | 2. **Test Solution preparation:** 1g sulphate weighed, 2mL HCl added to 45mL distilled water, then 5mL BaSO4 reagent added. 3. **Standard Solution preparation:** 1mL of 0.1089% w/v K2SO4 weighed, 2mL HCl added, diluted to 45mL water. 15mL of 0.5M BaCl2 mixed with 55mL SO4-free alcohol and 5mL of 0.0181% w/v K2SO4, then diluted to 100mL water. 4. Set aside for 5 minutes. 5. Check turbidity. - **Result:** If test solution turbidity ### Modified Limit Tests: Chloride and Sulphates - These tests overcome problems occurring during standard limit tests, especially with colored substances. #### For Chloride - Used for colored substances. - Colored substances can interfere with turbidity formation. - In modified limit tests, colored substances are converted to colorless substances to get clear turbidity. - Example: KMnO4 (potassium permanganate) - KMnO4 with purple color creates disturbance. - $$2KMnO_4 + 2C_2H_5OH \text{ (Redox reaction)} \rightarrow 2MnO_2 + 3CH_3CHO + 2KOH + 2H_2O$$ - Converts purple KMnO4 to colorless MnO2. - Procedure follows the standard limit test for chloride after this conversion. #### For Sulphate - Also used for colored substances that create interference. - KMnO4 example: purple color is converted to colorless MnO2, then the standard limit test procedure for sulphate is followed. ### Limit Test for Arsenic - **Purpose:** Identifies and controls arsenic impurities, an undesirable and harmful substance. - **Principle:** Arsenic (As) in arsenous acid state is converted to arsine gas ($AsH_3$) by reduction with zinc and hydrochloric acid. - $$H_3AsO_4 \xrightarrow{SnCl_2} H_3AsO_3 \text{ (Arsenic acid to Arsenous acid)}$$ - $$H_3AsO_3 + 6H \xrightarrow{Reduction} AsH_3 \uparrow + 3H_2O \text{ (Arsenous acid to Arsine gas)}$$ - Arsine gas then reacts with mercuric chloride paper to produce a yellow stain. - $$2AsH_3 + HgCl_2 \rightarrow Hg(AsH_3)_2 \text{ (Yellow stain)} + 2HCl$$ - The intensity of the yellow stain depends on the arsenic quantity and is compared with a standard solution. #### Apparatus: Gutzeit Apparatus - Consists of a 200mm long glass tube (8mm external, 6.5mm internal diameter) with a 2mm hole for gas. - Mercuric chloride paper and rubber cork. - During the test, arsine gas passes through a side hole to mercuric chloride paper. #### Procedure 1. Prepare test and standard solutions. 2. Place solutions in generator bottles with HI, IM KI, stannous chloride. 3. Add 10g Zinc (As-free) to both. 4. Keep solutions aside for 40 minutes. 5. Arsine gas reacts with HgCl paper to produce yellow stain. 6. Compare intensity/diameter of yellow stain. #### Precautions - Stain should be compared immediately as it fades. - Mercuric chloride paper should be stored in a dark place. - Tube should be washed with HCl (As-free), then water, and dried. ### Limit Test for Iron - **Purpose:** Identifies and controls iron impurities. - **Principle:** Iron reacts with thioglycolic acid (mercapto acetic acid) in the presence of ammonium citrate buffer, forming an iron thioglycolate complex with a purple color. - $$2Fe^{2+} + 2CH_2SH \text{ (Thioglycolic acid)} \rightarrow (CH_2S)_2Fe + 2H^+ \text{ (Iron thioglycolate complex, purple)}$$ - The intensity of the purple color is compared with a standard solution. Amount of iron impurities correlates with color intensity. #### Procedure 1. Prepare test and standard solutions. 2. **Test Solution:** Sample dissolved in water (up to 40mL), 2mL 20% w/v Citric acid (iron-free) added, 2 drops thioglycolic acid, then ammonia added to make solution alkaline (up to 50mL). 3. **Standard Solution:** 2mL standard iron solution diluted with water (up to 40mL), 2mL 20% w/v Citric acid (iron-free) added, 2 drops thioglycolic acid, then ammonia added to make solution alkaline (up to 50mL). 4. Keep aside for 5 minutes. 5. Compare developed color. ### Limit Test for Lead - **Purpose:** Identifies and controls lead impurities. - **Principle:** Lead reacts with diphenylthiocarbazone (dithizone) in alkaline solution to form a red lead dithizone complex. Dithizone is green in chloroform, and the lead-dithizone complex is violet/red. - $$Pb^{2+} + 2S=C(NHC_6H_5)_2 \text{ (Dithizone)} \rightarrow S=C(NHC_6H_5)_2Pb \text{ (Lead-dithizone complex, red)} + 2H^+$$ - The resulting red color is compared with a standard solution. #### Procedure 1. Prepare test and standard solutions. 2. **Test Solution:** Known quantity of sample solution transferred to a separating funnel. Add 6mL ammonium citrate, 2 drops phenol red, make alkaline with ammonia. 5mL dithizone solution used to extract until green. Combine extracts and transfer to second separator. Shake with 1% v/v nitric acid, discard chloroform layer. In this acid solution, add 5mL standard dithizone solution and 1mL ammonium cyanide. 3. **Standard Solution:** Standard lead solution transferred to a separating funnel, then same procedure as test solution. 4. Shake for 30 seconds and observe chloroform layer color. #### Observation/Result - If chloroform layer color in test solution is less intense than standard, sample passes. #### Precautions - Compare stain immediately as it fades. - All reagents/chemicals must be lead-free. - Glassware should be washed with dilute HNO3 and water. ### Limit Test for Heavy Metals - **Purpose:** Determines metallic impurities. - **Heavy Metals:** Chemical elements with high density, toxic or poisonous at low concentrations (e.g., Cadmium, Lead (Pb), Mercury (Hg), Arsenic (As), Chromium (Cr), Zinc (Zn), Bismuth (Bi), Cobalt, Silver). - **Principle:** Heavy metals ($M^{2+}$) react with hydrogen sulphide ($H_2S$) in acidic medium to form reddish/brown metal sulphides. - $$2M^{2+} + H_2S \xrightarrow{\text{Acidic medium}} M_2S \downarrow + 2H^+ \text{ (Metal sulphide)}$$ - The intensity of the color is compared with a standard solution. - Lead is typically used as the standard solution. The limit is usually 20ppm for lead. #### Procedure 1. Prepare test and standard solutions. 2. **Test Solution:** Specific quantity of sample dissolved in 25mL water in a 50mL Nessler cylinder. pH adjusted to 3-4 with dilute acetic acid/ammonia solution. Volume made up to 35mL water. Add 10mL H2S solution. 3. **Standard Solution:** 2mL standard lead solution in 25mL water in a 50mL Nessler cylinder. pH adjusted to 3-4 with dilute acetic acid/ammonia solution. Volume made up to 35mL water. Add 10mL H2S solution. 4. Keep aside for 5 minutes. 5. Compare color. #### Observation/Result - If color in test solution is less intense than standard, limit test passes. ### Unit 2: Syllabus #### Major Extracellular and Intracellular Electrolytes - Functions of major physiological ions. - Electrolytes used in replacement therapy: Sodium Chloride, Potassium Chloride, Calcium Gluconate, Oral Rehydration Salts (ORS). - Physiological acid-base balance. ### Body Fluids - Fluids present inside the human body. About 56% of human body is fluid. - Distributed into two types: 1. **Intracellular fluids:** Inside cells (45-50% of body weight). 2. **Extracellular fluids:** Outside cells (15-20% of body weight). - **Interstitial fluids:** Between cells (12-15%). - **Plasma:** Inside vascular system (blood) (4-5%). ### Electrolytes - **Definition:** Substances that ionize when dissolved in suitable ionizing solvents (like water). - Also known as ionic solutions due to the presence of ions (e.g., $$HCl \rightarrow H^+ + Cl^-$$, $$H_2O \rightarrow H^+ + OH^-$$, $$NaCl \rightarrow Na^+ + Cl^-$$). - In a solution, an electrolyte is considered if the ion concentration is high (concentrated) or low (diluted). - **Extracellular fluid:** Contains large amounts of ions ($Na^+$, $K^+$, $Cl^-$, $HCO_3^-$) and nutrients (oxygen, glucose, fatty acids, amino acids). - **Intracellular fluid:** Contains large amounts of potassium, magnesium, and phosphate ions. ### Functions of Major Physiological Ions - Ions/electrolytes maintain homeostasis and keep the body healthy. #### Major Ions/Electrolytes 1. **Calcium ($Ca^{2+}$):** - Important for teeth and bones, muscle contraction, and blood clotting. - Essential for growth in children. - **Sources:** Milk, cheese, green vegetables, eggs, fish. - **Functions:** Muscle contraction (actin filament activation), blood coagulation (prothrombin to thrombin), bone formation. - **Disease:** **Hypocalcemia** (low calcium), **Hypercalcaemia** (excess calcium). 2. **Chloride ($Cl^-$):** - Major extracellular anion. - Maintains osmotic pressure, proper hydration, and cation-anion balance. - **Sources:** Sea salt, table salt, seaweed, olives, tomatoes, rye, vegetables. - **Disease:** **Hypochloremia** (deficiency), **Hyperchloremia** (excess). 3. **Sodium ($Na^+$):** - Main extracellular cation. - Essential for maintaining osmotic pressure and normal hydration. - **Daily Requirement:** 2-5 gm/day. - **Sources:** Salt, buttermilk, cheese, fish, olives, pulses. - **Functions:** Heart function, blood pressure. - **Disease:** **Hyponatremia** (deficiency), **Hypernatremia** (excess). 4. **Potassium ($K^+$):** - Major intracellular cation. - Involved in nerve conduction with sodium through the sodium-potassium pump (also helps in pH regulation). - **Daily Requirement:** 3.5 gm/day. - **Sources:** Apricots, bananas, oranges. - **Disease:** **Hypokalemia** (deficiency), **Hyperkalemia** (excess). 5. **Phosphate ($PO_4^{3-}$):** - Principal intracellular anion. - Present in teeth and bones, acts as a buffer system. - **Daily Requirement:** 700 mg/day. - **Sources:** Protein-rich food, milk, meat. - **Functions:** Mild laxative, teeth and bone development, glucose metabolism. - **Disease:** **Hypophosphatemia** (deficiency), **Hyperphosphatemia** (excess). 6. **Magnesium ($Mg^{2+}$):** - Important intracellular cation. - Half of magnesium (10-20gm) combined with phosphorus and calcium in bone. - **Daily Requirement:** 270-350 mg/day. - **Sources:** Nuts, grains, green vegetables. - **Functions:** Glucose metabolism. - **Disease:** **Hypomagnesemia** (deficiency), **Hypermagnesemia** (excess). 7. **Bicarbonate ($HCO_3^-$):** - Second most prevalent extracellular anion. - Most important buffer system, maintains acid-base balance. - **Disease:** **Metabolic alkalosis** and **metabolic acidosis** due to bicarbonate deficiency. - Metabolic acidosis and kidney disturbance treated with sodium bicarbonate. ### Electrolytes Replacement Therapy (ORS) - **Purpose:** Maintain/overcome electrolyte imbalance due to vomiting, diarrhea, dehydration, or other diseases. - **Solutions:** Usually three types of compounds used in replacement therapy: 1. Sodium Chloride (NaCl) 2. Potassium Chloride (KCl) 3. Calcium Gluconate ($C_{12}H_{22}O_{14}Ca \cdot H_2O$) #### Sodium Chloride (NaCl) - **Molecular Weight:** 58.44 - **Molecular Formula:** NaCl - **Preparation:** Obtained from natural sources (rock salt, sea water). Purification is necessary due to impurities. - **Properties:** Colorless, white crystalline solid, odorless, freely soluble in water, salty/saline taste, pH 6.7-7.3. - **Chemical Reactions:** - With Silver Nitrate: $$NaCl + AgNO_3 \rightarrow AgCl \downarrow + NaNO_3$$ (forms silver chloride precipitate). - With Sulphuric Acid: $$2NaCl + H_2SO_4 \rightarrow 2HCl + Na_2SO_4$$ (forms hydrochloric acid). - **Uses:** Treatment of dehydration, replacement electrolyte. #### Potassium Chloride (KCl) - **Molecular Formula:** KCl - **Molecular Weight:** 74.55 gm/mol - **Preparation:** - From potassium carbonates: $$2HCl + K_2CO_3 \rightarrow 2KCl + H_2O + CO_2 \uparrow$$ - From potassium bicarbonate: $$HCl + KHCO_3 \rightarrow KCl + H_2O + CO_2 \uparrow$$ - **Properties:** Colorless, transparent, saline taste, soluble in water, insoluble in alcohol. - **Uses:** Replenishes potassium deficiency, used in electrolyte replacement therapy. #### Calcium Gluconate - **Molecular Formula:** $C_{12}H_{22}O_{14}Ca \cdot H_2O$ - **Molecular Weight:** 430.373 gm/mol - Calcium salt of gluconic acid, contains 9% calcium ions ($Ca^{2+}$). - **Preparation:** Gluconic acid solution heated with excess calcium carbonate. - $$2[HOCH_2-(CHOH)_4-COOH] + CaCO_3 \rightarrow Ca[HOCH_2-(CHOH)_4-COO]_2 + CO_2 \uparrow + H_2O$$ - **Properties:** White crystalline powder, odorless, tasteless, soluble in water, insoluble in alcohol. - **Chemical Reactions:** Undergoes decomposition with dilute mineral acids. - $$Ca(CHOH)_4(COO)_2Ca + 2HCl \rightarrow 2CH_2OH(CHOH)_4COOH + CaCl_2$$ - **Uses:** Electrolyte replacement, source of $Ca^{2+}$, treats burns from hydrofluoric acid, mental disorders, myasthenia gravis. #### Oral Rehydration Solutions (ORS) - **Purpose:** Treats fluid loss due to diarrhea, vomiting, or other diseases causing decreased body fluids. - Simple, cheap, and effective for dehydration. - Provides sodium, chloride, potassium, water, and other basic nutrients. ##### Composition of ORS (Standard vs. New WHO/UNICEF formula) | Composition | Amount (Standard) | Ions ($Na^+$) | Concentration (Standard) | |---------------|-------------------|---------------|--------------------------| | NaCl | 2.6 g | $Na^+$ | 75mM | | KCl | 1.5 g | $K^+$ | 20mM | | Trisodium Citrate | 2.9 g | $Cl^-$ | 65mM | | Glucose | 13.5 g | Citrate | 10mM | | Water | 1 L | Glucose | 75mM | | **Total Osmolarity** | **310 mOsm/L** | | **245 mOsm/L (New)** | - In acute diarrhea, $K^+$ loss is significant, so potassium is a chief constituent. - Citrate helps treat acidosis (due to alkali loss in stools) and promotes sodium and water absorption. ##### Administration - Drink ORS at regular intervals (1-1.5 hours). - Initially, 5-7.5% of body weight is given over 2-4 hours. ##### Side Effects - Hypernatremia ($Na^+$ excess) - Hyperkalemia ($K^+$ excess) ##### Uses - Oral Rehydration Therapy (ORT) is a simple, cheap, and effective treatment for dehydration caused by diarrhea. ### Physiological Acid-Base Balance - Body fluids contain acidic and basic fluids. - Acidic/basic nature depends on pH and $H^+$ ion concentration. - Low pH (acidic) = High $H^+$ concentration. - High pH (basic) = Low $H^+$ concentration. - pH level of fluids is crucial for proper function; large fluctuations cause severe damage (death). - Blood pH: 7.42 (range 6.8-8.0). Deviations cause damage. - Maintaining acid-base balance is vital. #### Mechanism of Acid-Base Balance 1. **Buffer System:** - Solutions that resist pH changes. - Made of weak acid/base and their salts. - Convert strong acids/bases into weak acids/bases. - **Bicarbonate buffer system:** Carbonic acid-bicarbonate buffer system. Bicarbonate maintains balance by reacting with $H^+$ ions. - Alkalosis (high pH, low $H^+$): Carbonic acid releases $H^+$ to maintain pH. - $$H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$$ - Acidosis (low pH, high $H^+$): Bicarbonate reacts with excess $H^+$ to maintain pH. - $$HCO_3^- + H^+ \rightleftharpoons H_2CO_3$$ - **Phosphate buffer system:** Phosphate present as monohydrogen phosphate ($HPO_4^{2-}$) and dihydrogen phosphate ($H_2PO_4^-$). - Acidosis (low pH, high $H^+$): Monohydrogen phosphate reacts with excess $H^+$. - $$HPO_4^{2-} + H^+ \rightarrow H_2PO_4^-$$ - Alkalosis (high pH, low $H^+$): Dihydrogen phosphate releases $H^+$. - $$H_2PO_4^- \rightarrow HPO_4^{2-} + H^+$$ 2. **Renal System:** - Kidneys maintain acid-base balance through absorption and elimination. - Acidosis (low pH, high $H^+$): Excess $H^+$ ions eliminated, bicarbonate ions ($HCO_3^-$) reabsorbed. - Alkalosis (high pH, low $H^+$): $H^+$ ions decreased. 3. **Respiratory System:** - Lungs maintain acid-base balance by controlling $CO_2$ (carbon dioxide) levels. - **Acidosis:** Brain receptors stimulate increased respiration rate, leading to decreased blood $CO_2$ and increased pH. - **Alkalosis:** Brain receptors stimulate decreased respiration rate, leading to increased blood $CO_2$ and decreased pH. - Homeostasis restored when balance is achieved. ### Unit 2: Chapter 3 Syllabus #### Dental Products - Dentifrices. - Role of fluoride in treating dental caries. - Desensitizing agents. - Calcium carbonate. - Sodium fluoride. - Zinc eugenol cement. ### Dental Products - **Definition:** Products used to treat dental caries and maintain dental health. - Dental hygiene is important to prevent teeth problems. #### Tooth Structure - Consists of three layers: 1. **Enamel:** White, hard material covering the tooth (98% minerals), hardest part of the body. Main component: Hydroxyapatite ($Ca_{10}(PO_4)_6(OH)_2$). 2. **Dentine:** Covers pulp cavity and entire portion of tooth. 3. **Cementum:** Layer covering the buried portion of tooth. ### Anti-Caries Agents - **Definition:** Agents that treat dental caries (tooth decay), which is decalcification of tooth, often with foul mouth odor. #### Dental Caries/Tooth Decay - A dental problem caused by acids produced by microorganisms on carbohydrates (present on teeth). - Causes cavities, decalcification, damage, and foul mouth odor. - Fluoride is the main substance used as an anti-caries agent. #### Role of Fluoride in Dental Caries Treatment - Fluoride is the main substance used for dental caries/tooth decay. - Present in trace amounts in the human body, obtained from food and water. - Lack of fluoride in ground water can lead to dental problems. #### Administration - Fluorides can be administered orally or topically. - **Oral/Internally:** Rapidly absorbed, transported, and deposited in developing teeth and bone. Excreted through kidneys. - **Topically:** Applied to tooth surface, prevents dental caries, avoids lesions due to acids/enzymes. - **Quantity:** Small quantity (1 ppm) usually added to preparations. More than 2-3 ppm can cause mottling of tooth enamel, increased bone density, gastric disturbance, muscular weakness, and heart failure. #### Mechanism - Fluorides reduce bacterial acid production or remineralize tooth areas. - Fluoride ion ($F^-$) replaces hydroxyl ion ($OH^-$) in hydroxyl apatite (enamel's crystalline structure) to form fluorapatite. - $$Ca_{10}(PO_4)_6(OH)_2 + 2F^- \rightarrow Ca_{10}(PO_4)_6F_2 + 2(OH)^-$$ - Fluorapatite is more resistant to acids produced by plaque bacteria. ### Sodium Fluoride (NaF) - **Molecular Weight:** 41.99 g/mol - Colorless inorganic compound, a source of fluoride ions. #### Methods of Preparation 1. **Hydrogen Fluoride (HF) and Sodium Carbonate:** - $$2HF + Na_2CO_3 \rightarrow 2NaF + H_2O + CO_2$$ 2. **Calcium Fluoride ($CaF_2$) and Sodium Carbonate:** - $$CaF_2 + Na_2CO_3 \rightarrow 2NaF + CaCO_3$$ #### Properties - Colorless/white powder. - Odorless solid with 993°C melting point. - Soluble in water, insoluble in alcohol. #### Uses - Oral hygiene for preventing dental caries. - Makes tooth enamel resistant to acid. - Promotes re-mineralization. - Reduces production of microbial acids. ### Dentifrices - **Definition:** Anticaries agents that clean reachable tooth surfaces with a toothbrush/fingers. - Maintain good oral hygiene. - Remove dental plaque and food debris. - Fluorides are also present in dentifrices. - **Examples:** Toothpaste, Tooth Powder, Mouthwash. #### Calcium Carbonate ($CaCO_3$) - **Molecular Weight:** 100.09 g/mol - Precipitated calcium carbonate or precipitated chalk. ##### Method of Preparation - Mined and processed from natural mineral sources. - Combining Calcium Oxide (CaO) with water to produce Calcium Hydroxide ($Ca(OH)_2$), then treated with Carbon Dioxide ($CO_2$). - $$CaO + H_2O \rightarrow Ca(OH)_2$$ - $$Ca(OH)_2 + CO_2 \rightarrow CaCO_3 + H_2O$$ ##### Properties - White, fine powder with 825°C melting point. - Odorless, tasteless. - Releases Carbon Dioxide ($CO_2$) when reacting with strong acids. - $$CaCO_3 + 2HCl \rightarrow CaCl_2 + CO_2 + H_2O$$ ##### Uses - Used in toothpastes and toothpowders as a dental cleaning and polishing agent. - Inexpensive dietary calcium supplement or antacid. ### Desensitizing Agents - **Definition:** Agents that relieve painful sensation in teeth. - Painful sensation occurs due to dental caries or tooth decay, or when teeth are exposed to hot or cold environments. - **Examples:** Zinc Chloride, Silver Nitrate, Corticosteroids (anti-inflammatory). #### Zinc Chloride ($ZnCl_2$) - **Molecular Weight:** 136.28 g/mol ##### Preparation - Heating granulated Zinc (Zn) with HCl. - $$Zn + 2HCl \rightarrow ZnCl_2 + H_2$$ ##### Properties - Odorless, white crystalline powder. ##### Uses - Desensitizer. - Antiseptic. ### Zinc Eugenol Cement - **Definition:** Material created by combining zinc oxide and eugenol (from clove oil). - Also known as zinc oxide eugenol (ZOE). - Used in dentistry to fill tooth cavities, treating dental caries, and in Root Canal Therapy (RCT). #### Composition - **Solid/Powder:** Zinc oxide (~69.0%), Zinc acetate (~1.0%), Zinc stearate (~0.7%), White resin (~29.3%). - **Liquids:** Eugenol (~85%), Olive oil (~15%). #### Uses - Dental filling or cement material. - Temporary filling for treating dental caries. ### Unit 3: Syllabus #### Gastrointestinal Agents - **Acidifiers:** Ammonium chloride, Dil. HCl. - **Antacids:** Ideal properties, combinations, Sodium Bicarbonate, Aluminium hydroxide gel, Magnesium hydroxide mixture. - **Cathartics:** Magnesium sulphate, Sodium orthophosphate, Kaolin, Bentonite. - **Antimicrobials:** Mechanism, classification, Potassium permanganate, Boric acid, Hydrogen peroxide, Chlorinated lime, Iodine and its preparations. ### Gastrointestinal Agents - **Definition:** Drugs that treat gastrointestinal (GI) disorders. - Involve inorganic and organic drugs. - **Examples:** Acidifiers (Dil. HCl), Antacids (sodium bicarbonate). - GI disorders are conditions occurring in the GI tract. #### Gastrointestinal Tract - Important body system. - Consists of oral cavity, pharynx, esophagus, stomach, small intestine, and anal canal. - Pathway of digestive system. #### GI Tract Functions - Digestion and absorption of nutrients. - Excretion of waste products. - **Stomach:** Produces and contains hydrochloric acid (HCl), crucial for digestion. - Excess HCl: Hyperacidity, ulcer. - HCl deficiency: Achlorhydria or hypochlorhydria (decreased digestion). - **Intestines:** Absorption and movement of food, excretion of waste (stool). - Slow movement: Constipation (treated by cathartics). - **Microbes:** Can affect GI tract; prevented by antimicrobial agents. ### Acidifiers - **Definition:** Inorganic substances that increase metabolic acidosis or gastric acid in the GI tract (stomach). - Work by increasing stomach acid or by increasing the level of acid. #### Classification 1. **Gastric Acidifiers:** Treat achlorhydria or hypochlorhydria, restoring stomach acidity. 2. **Urinary Acidifiers:** Control urine pH to treat urinary tract infections. 3. **Systemic Acidifiers:** Control body pH by neutralizing alkaline body fluids. #### Ammonium Chloride ($NH_4Cl$) - **Molecular Formula:** $NH_4Cl$ - **Molecular Weight:** 53.50 gm/mol ##### Method of Preparation - Ammonia gas reacts with hydrochloric acid, then dried by evaporation. - $$NH_3 + HCl \rightarrow NH_4Cl$$ - Ammonia sulphate reacts with Sodium Chloride. - $$(NH_4)_2SO_4 + 2NaCl \rightarrow 2NH_4Cl + Na_2SO_4$$ ##### Properties - White, crystalline powder. - Slightly hygroscopic, odorless, inorganic salt with a cooling saline taste. - Freely soluble in water, sparingly soluble in alcohol. - **Chemical Reaction:** On hydrolysis, gives ammonium hydroxide. - $$NH_4Cl + H_2O \rightarrow NH_4OH + HCl$$ - On decomposition, releases ammonia gas. - $$NH_4Cl \xrightarrow{\Delta} NH_3 \uparrow + HCl$$ ##### Uses - Acidifier to treat achlorhydria. - Fertilizers, expectorants in cough preparations. #### Dilute Hydrochloric Acid (Dil. HCl) - **Molecular Formula:** HCl - **Molecular Weight:** 36.46 gm/mol - Solution of hydrogen chloride in water (9-10% w/v). ##### Method of Preparation - Sulphuric acid reacts with sodium chloride, and HCl gas is passed through water. - $$H_2SO_4 + 2NaCl \rightarrow Na_2SO_4 + 2HCl$$ ##### Properties - Clear, colorless, strong acidic solution. - Pungent odor. - Soluble in water and alcohol. - Gives $H^+$ ions when reacting with water. - $$HCl + H_2O \rightarrow H_3O^+ + Cl^-$$ ##### Uses - Acidifier, treats achlorhydria. - Pharmaceutical aid (solvent). ### Antacids - **Definition:** Substances that neutralize excess stomach acid. - Mainly treat hyperacidity (excess HCl in stomach), gastritis, heartburn, and peptic ulcers. #### Ideal Properties - Rapid action and prolonged effect. - Does not cause constipation. - pH range 4-6. - Does not cause metabolic alkalosis. - Does not interfere with food absorption. #### Mechanism - Basic substances that neutralize excess acid and maintain acid-base balance. - $$Antacid + HCl \rightarrow \text{Salt} + H_2O$$ #### Classification 1. **Systemic Antacids:** Absorbed into blood circulation, soluble, can cause metabolic alkalosis (e.g., Sodium Bicarbonate). 2. **Non-Systemic Antacids:** Not absorbed into blood, act locally in stomach to decrease acidity (e.g., Aluminium hydroxide, Magnesium hydroxide). #### Sodium Bicarbonate ($NaHCO_3$) - **Molecular Formula:** $NaHCO_3$ - **Molecular Weight:** 84.01 gm/mol - Contains 99-101% $NaHCO_3$. ##### Method of Preparation 1. **Ammonia Bicarbonate and Sodium Chloride:** - $$NH_4HCO_3 + NaCl \rightarrow NaHCO_3 \downarrow + NH_4Cl$$ 2. **Sodium Carbonate, Water, and Carbon Dioxide:** - $$Na_2CO_3 + H_2O + CO_2 \rightarrow 2NaHCO_3$$ ##### Properties - Odorless, white crystalline powder. - Slightly alkaline taste. - Stable in dry air, sparingly soluble in water, insoluble in organic solvents. ##### Uses - Antacid for neutralizing acid. - Buffer solution. - Local applicant for burns, insect bites. #### Aluminium Hydroxide Gel ($Al(OH)_3$) - **Molecular Formula:** $Al(OH)_3$ - **Molecular Weight:** 78.00 gm/mol - Contains 3.5-4.4% w/w aluminium oxide ($Al_2O_3$). ##### Method of Preparation - Aluminium salt (aluminium chloride) reacts with ammonium hydroxide. - $$AlCl_3 + 3NH_4OH \rightarrow Al(OH)_3 \downarrow + 3NH_4Cl$$ ##### Properties - White colored gel, soluble in acids and alkalis. - Odorless, tasteless. - Melting point 300°C. ##### Uses - Antacid. - Used with magnesium hydroxide for better effect. #### Magnesium Hydroxide Mixture ($Mg(OH)_2$) - **Molecular Formula:** $Mg(OH)_2$ - **Molecular Weight:** 58.3197 g/mol - Also known as milk of magnesia. - Contains 95-100.5% $Mg(OH)_2$. ##### Method of Preparation - Magnesium sulphate reacts with sodium hydroxide. - $$MgSO_4 + 2NaOH \rightarrow Mg(OH)_2 \downarrow + Na_2SO_4$$ ##### Properties - White, colored, opaque, more/less viscous suspension. - Odorless. ##### Uses - Non-systemic gastric antacid. - Mild cathartic. #### Combinations of Antacids - Used to fulfill all ideal antacid criteria. - **Aluminum hydroxide gel + Magnesium trisilicate:** Laxative, protective, constipated. - **Calcium carbonate + Antacid mixtures:** Prolonged action with rapid onset. ### Cathartics - **Definition:** Agents that facilitate defecation (bowel movement) to treat constipation. #### Constipation - Condition where a person passes less than three bowel movements per week or has difficult defecation. - Defecation is the process of passing stool, mainly depends on peristaltic (bowel) movement. - Occurs due to continuously ignoring the urge to defecate, weak intestines, intestinal spasm, injury, certain drugs, diet. - Fecal material becomes dry and hard. #### Classification 1. **Stimulants:** Increase bowel movement by local irritation of intestinal tract (e.g., Senna, Aloevera, Castor oil). 2. **Bulk Purgatives:** Increase intestinal content bulk to increase bowel movement (e.g., Ispagol, Cellulose). 3. **Lubricants:** Act as lubricants and increase flow for emptying bowel (e.g., Liquid paraffin, Glycerin). 4. **Saline Cathartics:** Increase osmotic load of intestine, increasing bowel movement (e.g., Calcium, Magnesium). #### Magnesium Sulphate ($MgSO_4 \cdot 7H_2O$) - **Molecular Formula:** $MgSO_4 \cdot 7H_2O$ - **Molecular Weight:** 246.47 g/mol - Also known as Epsom salt. ##### Method of Preparation - Neutralization reaction between hot dilute sulphuric acid and magnesium oxide. - $$H_2SO_4 + MgO \rightarrow MgSO_4 + H_2O$$ - From magnesium carbonate. - $$H_2SO_4 + MgCO_3 \rightarrow MgSO_4 + H_2O + CO_2$$ ##### Properties - White crystalline solid, bitter taste. - Soluble in water, slightly soluble in alcohol/glycerol. - Decomposes and evolves sulphur trioxide on heating. - $$MgSO_4 \xrightarrow{\Delta} MgO + SO_3 \uparrow$$ ##### Uses - Purgative. - Anti-convulsive agent. #### Sodium Orthophosphate ($Na_2HPO_4 \cdot 12H_2O$) - **Molecular Formula:** $Na_2HPO_4 \cdot 12H_2O$ - **Molecular Weight:** 358.14 g/mol - Also known as disodium hydrogen orthophosphate or sodium phosphate. ##### Preparation - Sodium carbonate reacts with hot phosphoric acid. - $$Na_2CO_3 + H_3PO_4 \rightarrow Na_2HPO_4 + H_2O + CO_2$$ ##### Properties - Colorless, transparent crystals, bitter, salty taste. - Soluble in water, insoluble in alcohol. ##### Chemical Reaction - On reducing, produces sodium iodide and sodium tetrathionate. - $$2Na_2S_2O_3 + I_2 \rightarrow 2NaI + Na_2S_4O_6$$ ##### Uses - Saline laxative, buffering agent, cathartic. #### Kaolin - **Molecular Formula:** $Al_2O_3 \cdot 2SiO_2 \cdot 2H_2O$ - **Molecular Weight:** 258.09 g/mol - Natural, purified, hydrated aluminium silicate (china clay). ##### Preparation - Simply prepared by powdering, separating, and purifying natural clay. ##### Properties - White powder (clay), odorless, tasteless. ##### Uses - Cathartic. - Treats food poisoning, colitis, and cholera. #### Bentonite - **Molecular Formula:** $Al_2O_3 \cdot 4SiO_2 \cdot H_2O$ - **Molecular Weight:** 360.3 g/mol - Also known as Wilkinite. ##### Preparation - Purification of crude bentonite. ##### Properties - Odorless, pale bluff, cream colored powder. - Soluble in water. ##### Uses - Cathartic. - Emulsifier. ### Antimicrobials - **Definition:** Agents or drugs that kill or inhibit microorganism growth. - **Microbicidal:** Kill microbes. - **Microbiostatic:** Prevent microbe growth. #### Classification 1. **Antiseptics:** Inhibit microbial growth on living cells (e.g., H2O2). Used in mouthwashes, soaps, deodorants, throat/nasal sprays. 2. **Disinfectants:** Kill pathogenic microorganisms on non-living objects (e.g., Sulphur dioxide). Used to maintain hygiene in home/hospitals. 3. **Germicides:** Kill microorganisms on both living and non-living surfaces. Also known as bactericide, fungicide, virucide. 4. **Bacteriostatic:** Prevent bacterial growth without killing. 5. **Sanitizers:** Disinfectants maintaining health standards by cleaning hands (e.g., Alcohols). #### Mechanism of Antimicrobials 1. **Oxidation:** Oxidize active functional groups in protein/enzymes, preventing microbe growth. 2. **Halogenation:** Act on peptide linkage, damaging protein functional groups, leading to microbial death (e.g., Iodine, Chlorine). 3. **Precipitation:** Metal ions bind to protein or cause protein precipitation, inactivating the protein. #### Potassium Permanganate ($KMnO_4$) - **Molecular Weight:** 158 g/mol - Also known as permanganate of potash or Condy's crystal. ##### Preparation - Oxidizing potassium manganate with chlorine under acidic conditions. - $$2K_2MnO_4 + Cl_2 \rightarrow 2KMnO_4 + 2KCl$$ - From potassium manganate with sulphuric acid. - $$3K_2MnO_4 + 4HCl \rightarrow 2KMnO_4 + MnO_2 + 2H_2O + 4KCl$$ ##### Properties - Dark purple color. - Odorless, sweetish astringent taste. - Soluble in water, alcohol. ##### Uses - Antiseptic, disinfectant, germicidal, bleaching agent, tooth whitening. #### Boric Acid ($H_3BO_3$) - **Molecular Weight:** 61.83 gm/mol - Also known as hydrogen borate. ##### Preparation - Borax reacts with sulphuric acid, followed by water addition. - $$Na_2B_4O_7 + H_2SO_4 + 5H_2O \rightarrow Na_2SO_4 + 4H_3BO_3$$ ##### Properties - White crystalline solid. - Odorless, sweet taste. - Soluble in water, slightly soluble in alcohol. ##### Uses - Eyewash, mouthwash. - Insecticide, bacteriostatic. - Buffer, dusting powder. #### Hydrogen Peroxide ($H_2O_2$) - **Molecular Weight:** 34 g/mol - Simplest stable peroxide, also known as perhydroxide acid. ##### Preparation - Sodium peroxide reacts with cold dilute sulphuric acid. - $$Na_2O_2 + H_2SO_4 \rightarrow H_2O_2 + Na_2SO_4$$ ##### Properties - Clear, colorless liquid. - Odorless, bitter acidic taste. - Soluble in water. - Dissociates into water and oxygen on heating. - $$2H_2O_2 \xrightarrow{\Delta} 2H_2O + O_2$$ ##### Uses - Antiseptic, topical antifungal agent. - Treats skin infections. #### Chlorinated Lime ($CaOCl_2 \cdot H_2O$) - **Molecular Weight:** 142.98 g/mol - Also known as calcium hypochlorite and bleaching powder. ##### Preparation - Chlorine gas reacts with calcium hydroxide at 25°C. - $$Ca(OH)_2 + Cl_2 \rightarrow CaOCl_2 + H_2O$$ ##### Properties - White or grey powder. - Strong odor of chlorine. - Partially soluble in water, alcohol. ##### Uses - Antimicrobial, bactericidal. - Bleaching agent, antiseptic, disinfectant. - Used in diphtheria, scarlet fever. #### Iodine ($I_2$) - **Molecular Weight:** 253.8 g/mol - Belongs to halogens, 99.5% purity. ##### Preparation - Potassium iodide reacts with dilute sulphuric acid and manganese dioxide. - $$2KI + MnO_2 + 3H_2SO_4 \rightarrow I_2 + 2KHSO_4 + MnSO_4 + 2H_2O$$ ##### Properties - Greyish-violet or bluish-black crystals. - Strong odor, volatile in nature. - Insoluble in water, soluble in alcohol. ##### Uses - Disinfectant, antimicrobial agent. - Treats iodine deficiency. - X-ray, radiocontrast agent. - Best antiseptic. ##### Iodine Preparations - Aqueous iodine solution. - Povidone iodine. - Sodium iodide (NaI). ### Activated Charcoal - **Definition:** Residue obtained from destructive distillation of various organic materials. - Prepared by using organic wastes like sucrose, lactose, rice, starch, coconut. - Acts by its absorptive power. #### Properties - Fine, black, odorless, tasteless powder. - Insoluble in water and other organic solvents. #### Medicinal Uses - Emergency antidote for poisoning. - Adsorbs alkaloids, NH3, CO, CO2, O2, N2, NO2, H2. - Used in filters of gas masks. ### Astringents - **Definition:** Substances that cause protein precipitation. - Applied topically on damaged skin, mucous membranes of GI tract, forming a protective layer. #### Mechanism - Form a protective layer. - Protects against bacteria and infections. - Prevents capillary leakage in bleeding areas. - Reduces local edema, exudation, inflammation, and mucus secretion. - Reduces cell permeability by precipitating proteins. #### Zinc Sulphate ($ZnSO_4 \cdot 7H_2O$) - **Molecular Weight:** 287.54 g/mol - Also known as white vitriol. ##### Preparation - Zinc oxide reacts with dilute sulphuric acid. - $$ZnO + H_2SO_4 \rightarrow ZnSO_4 + H_2O$$ ##### Properties - White crystalline solid. - Odorless. - Soluble in water, insoluble in alcohol. ##### Uses - Astringent, antiseptic, eye lotion, emetic. #### Potash Alum ($KAl(SO_4)_2 \cdot 12H_2O$) - **Molecular Weight:** 474.4 g/mol - Also known as potassium aluminium sulphate. ##### Preparation - Mixing a concentrated solution of potassium sulphate with hot solution of aluminium sulphate. - $$K_2SO_4 + Al_2(SO_4)_3 + 12H_2O \rightarrow 2KAl(SO_4)_2 \cdot 12H_2O$$ ##### Properties - Colorless, transparent or granular crystals. - Sweet astringent taste. - Soluble in water, insoluble in alcohol. ##### Medicinal Uses - Topically as astringent. - Antiseptic. - Pharmaceutical aid. ### Unit 4: Syllabus #### Miscellaneous Compounds - **Expectorants:** Potassium Iodide, Ammonium Chloride. - **Emetics:** Copper Sulphate, Sodium Potassium Tartarate. - **Haematinics:** Ferrous Sulphate, Ferrous Gluconate. - **Poison & Antidote:** Sodium Thiosulphate, Activated Charcoal. - **Astringents:** Zinc Sulphate, Potash Alum. - **Sodium Nitrite.** ### Expectorants - **Definition:** Agents/drugs that help expel sputum (mucus + cell debris + foreign particles) from the respiratory tract, treating cough. - Cough is a protective reflex. - Mucus (sputum) expulsion is the goal. #### Classification 1. **Secretion Enhancers:** Increase bronchial secretion, diluting sputum and aiding removal (e.g., Guaifenesin, Potassium Iodide, Ammonium Chloride). 2. **Mucolytics:** Break down mucus (e.g., Bromhexine, Ambroxol). #### Potassium Iodide (KI) - **Molecular Formula:** KI - **Molecular Weight:** 166 g/mol ##### Preparation - Potassium bicarbonate reacts with hydrogen iodide. - $$KHCO_3 + HI \rightarrow KI + H_2O + CO_2$$ - Also prepared by treating hot aqueous solution of potassium hydroxide with iodine. - $$2KOH + I_2 \rightarrow KI + KIO + H_2O$$ ##### Properties - Odorless, transparent, saline bitter taste. - Soluble in alcohol/water, insoluble in glycerin. - Hygroscopic. ##### Uses - Expectorant. - Source of potassium and iodine. - Reagent in pharmacy. #### Ammonium Chloride ($NH_4Cl$) - **Molecular Formula:** $NH_4Cl$ - **Molecular Weight:** 53.50 gm/mol ##### Preparation - Neutralizing ammonia with HCl, then evaporating and drying. - $$NH_3 + HCl \rightarrow NH_4Cl$$ - Ammonia sulphate reacts with Sodium Chloride. - $$(NH_4)_2SO_4 + 2NaCl \rightarrow 2NH_4Cl + Na_2SO_4$$ ##### Properties - White crystalline powder. - Odorless, transparent, saline taste. - Soluble in water, glycerin, sparingly soluble in alcohol. - Hygroscopic. ##### Uses - Expectorant, acidifier, diuretic. ### Emetics - **Definition:** Drugs that induce vomiting to empty the stomach. - Vomiting is the forceful expulsion of gastric content through the mouth. - Used for poisoning, drug overdose, but can have adverse effects. #### Mechanism - Remove fluids from respiratory tract by stimulating secretion. - **Chemoreceptor Trigger Zone (CTZ):** Emetics stimulate CTZ in the medulla oblongata, which stimulates the vomiting center (e.g., Morphine, Digitalis). - **GIT Irritation:** Irritating the GIT increases secretion and movement (e.g., Zinc sulphate, Copper sulphate, Sodium chloride). #### Characteristics - Non-toxic, non-irritant. - Non-interactive with other drugs. - Short onset of action. #### Copper Sulphate ($CuSO_4 \cdot 5H_2O$) - **Molecular Formula:** $CuSO_4 \cdot 5H_2O$ - **Molecular Weight:** 159.6 g/mol - Also known as blue vitriol. ##### Preparation - Dissolving cupric carbonate in dilute sulphuric acid. - $$CuCO_3 + H_2SO_4 \rightarrow CuSO_4 + H_2O + CO_2$$ - Granulated copper reacts with sulphuric acid in presence of air. - $$2Cu + 2H_2SO_4 + O_2 \rightarrow 2CuSO_4 + 2H_2O$$ ##### Properties - Deep blue crystals. - Odorless. - Soluble in water, insoluble in alcohol. ##### Uses - Emetic, fungicide. #### Sodium Potassium Tartarate ($C_4H_4KNaO_6$) - **Molecular Formula:** $C_4H_4KNaO_6$ - **Molecular Weight:** 210.158 g/mol - Also known as Rochelle salt. ##### Preparation - Neutralizing potassium bitartrate with sodium carbonate. - $$2KHC_4H_4O_6 + Na_2CO_3 + H_2O \rightarrow 2KNaC_4H_4O_6 + 2H_2O + CO_2$$ ##### Properties - White/colorless crystalline powder. - Odorless, saline taste. - Soluble in water, insoluble in alcohol. ##### Uses - Emetic, saline cathartic. ### Haematinics - **Definition:** Drugs/agents that increase hemoglobin or iron concentration in blood. - Treat anemia (iron-deficiency anemia). #### Anemia - Condition of decreased hemoglobin/blood in the body, or RBC loss. - **Causes:** Blood loss (acute/chronic), trauma, hemorrhage, decreased RBC formation. #### Ferrous Sulphate ($FeSO_4 \cdot 7H_2O$) - **Molecular Formula:** $FeSO_4 \cdot 7H_2O$ - **Molecular Weight:** 278 g/mol - Contains 20% iron. Also known as green vitriol. ##### Preparation - Iron reacts with dilute sulphuric acid. - $$Fe + H_2SO_4 \rightarrow FeSO_4 + H_2 \uparrow$$ - Iron pyrites exposed to air and moisture. - $$2FeS_2 + 7O_2 + 2H_2O \rightarrow 2FeSO_4 + 2H_2SO_4$$ ##### Properties - Pale, bluish-green crystals or granules. - Odorless, bitter saline taste. - Soluble in water, insoluble in alcohol. - Decomposes into sulphur dioxide, sulphur trioxide, and ferric oxide salts on heating. - $$2FeSO_4 \xrightarrow{\Delta} Fe_2O_3 + SO_2 + SO_3$$ ##### Uses - Haematinic, treats anemia. #### Ferrous Gluconate ($C_{12}H_{22}FeO_{14} \cdot 2H_2O$) - **Molecular Formula:** $C_{12}H_{22}FeO_{14} \cdot 2H_2O$ - **Molecular Weight:** 482.18 g/mol - Contains 12% iron. ##### Preparation - Ferrous carbonate reacts with gluconic acid solution. - $$FeCO_3 + 2C_6H_{12}O_7 \rightarrow Fe(C_6H_{11}O_7)_2 + H_2O + CO_2 \uparrow$$ ##### Properties - Yellowish-grey powder. - Burnt sugar odor. - Soluble in cold water, insoluble in alcohol. ##### Uses - Haematinic, treats iron deficiency anemia. - Used in elixir form. ### Poison & Antidote #### Poison - **Definition:** Any substance causing illness or death upon administration. - Administered intentionally (to harm oneself) or unintentionally (accidentally, overdose). - **Symptoms:** Breathing problems, decreased heart rate, dilated pupils, vomiting, diarrhea. #### Antidotes - **Definition:** Agents that neutralize or treat the effects of poison. #### Classification by Mechanism 1. **Mechanical Antidotes:** Prevent poison absorption (e.g., activated charcoal). 2. **Physiological Antidotes:** Produce opposite effects of poison (e.g., Sodium Nitrite). 3. **Chemical Antidotes:** Alter/change poison's chemical nature, converting it to an inactive/harmless compound (e.g., Sodium Thiosulphate). #### Mechanism of Cyanide Poisoning Antidote - Cyanide inhibits cellular respiration by binding to cytochrome oxidase. - **Antidote:** Sodium Nitrite (NaNOL) converts hemoglobin (Hb) to methemoglobin ($MetHb$), which has a higher affinity for cyanide, forming cyanomethemoglobin, releasing cytochrome oxidase. - $$Hb + Nitrite \rightarrow MetHb$$ - $$MetHb + CN^- \rightarrow CyanometHb$$ - Sodium Thiosulphate converts cyanide to thiocyanate (SCN), which is water-soluble and excreted. - $$CN^- + S_2O_3^{2-} \rightarrow SCN^- + SO_3^{2-}$$ ### Sodium Thiosulphate ($Na_2S_2O_3 \cdot 5H_2O$) - **Molecular Formula:** $Na_2S_2O_3 \cdot 5H_2O$ - **Molecular Weight:** 248.18 g/mol - Also known as sodium hyposulphate. - Contains 99-100.5% $Na_2S_2O_3$. #### Preparation - Sulphite solution reacts with boiled powdered sulphur. - $$Na_2SO_3 + S \rightarrow Na_2S_2O_3$$ - Sulphur dioxide gas passes through sodium sulphide solution. - $$2Na_2S + 3SO_2 \rightarrow 2Na_2S_2O_3 + S$$ #### Properties - Colorless, transparent crystals, bitter salty taste. - Soluble in water, insoluble in alcohol. #### Chemical Reaction - On reducing, produces sodium iodide and sodium tetrathionate. - $$2Na_2S_2O_3 + I_2 \rightarrow 2NaI + Na_2S_4O_6$$ #### Uses - Chemical antidote for cyanide poisoning. - Antiseptic, topical antifungal agent. - Treats skin infections. ### Unit 5: Syllabus #### Radiopharmaceuticals - Radioactivity. - Measurement of radioactivity. - Properties of alpha, beta, gamma radiations. - Half-life. - Study of radioisotopes. - Sodium Iodide I-131. - Storage conditions. - Preparations and pharmaceutical applications of radioactive substances. ### Radiopharmaceuticals - **Definition:** Radioactive substances used therapeutically for treatment and diagnosis. - Distributed in the body and emit radiations, used to detect injury, abnormal cell growth, and fractures. - X-rays: Pass through body tissue, muscle, but not bones, providing images. #### Radioactivity - **Definition:** Phenomenon where unstable radioisotopes undergo decomposition or decay by emitting radiation/rays to become stable. - Radiations are emitted from the nucleus of an element. - **Types of Radiations:** Alpha ($\alpha$), Beta ($\beta$), and Gamma ($\gamma$). ### Radiation - **Definition:** Radioactive substances emit radiations that travel through and are absorbed by a medium. #### Alpha ($\alpha$) Rays - **Characteristics:** Positively charged particles (2 unit charges), heavy. - Least penetrating power. - Equivalent to Helium nuclei ($^4He$). - Highly energetic, up to 9 MeV. - Less useful in pharmaceutical formulation. - Example: $$^{226}Ra \rightarrow ^{222}Rn + ^4He (\alpha)$$ #### Beta ($\beta$) Rays - **Characteristics:** Mostly negative charged particles (negatron or electron), rarely positive (positron). - Great penetrating power compared to $\alpha$-rays. - Mass equal to an electron (approx. 1/1800 of unit mass). - Example: $$^{14}C \rightarrow ^{14}N + \beta^-$$ #### Gamma ($\gamma$) Radiation - **Characteristics:** Electromagnetic radiation. - No mass or charge, neutral. - More penetrating power than $\alpha$ and $\beta$ rays. - Travels at the speed of light. - High energy particles, typically 2 MeV. ### Applications of Radiations - Diagnostic purposes (e.g., X-rays). - Sterilization (destroy bacteria, microbes). - Power supply for satellites, electricity for space labs. - Estimating air pollution. ### Units of Radioactivity - Refers to the number of disintegrations per second. 1. **Curie (Ci):** - Conventional unit. - 1 Ci = $3.7 \times 10^{10}$ disintegrations per second (dps) or 37 trillion decay. 2. **Becquerel (Bq):** - SI unit. - 1 Bq = $2.703 \times 10^{-11}$ Ci (1 disintegration per second). 3. **Roentgen (R):** - International system of units. - 1 R = $2.58 \times 10^{-4}$ C/kg. ### Decay Constant and Half-Life - **Decay Constant ($\lambda$):** Actual amount of emission per unit time. - $$\lambda = -dN/dt / N$$ - $$\lambda = 2.303/t \log(N_0/N)$$ - **Half-life ($t_{1/2}$):** Time period for a substance or radionuclide to reduce by 50%. - $$t_{1/2} = 0.693 / \lambda$$ - **Examples:** Iodine-131 (8 days), Polonium-212 (3 x $10^{-7}$ seconds), Uranium-238 (4.5 x $10^9$ years). ### Measurement of Radioactivity - Alpha, beta, and gamma radioactivity measured by various techniques: 1. **Ionization Chamber:** - Measures radiation strength by current strength. - Two metallic plates separated by air. Radiation knocks off air molecules, forming charged particles. Electrons move to anode, positive ions to cathode, forming current. - Total charge measured by dosimeter. 2. **Geiger-Muller Counter:** - Detects and measures $\alpha$ or $\beta$ particles. - Cylindrical metal tube (cathode) with an anode wire. Filled with argon gas. - Radiation ionizes argon, creating A+ + e-. Current flows, amplified and counted. - Very low pressure (0.1 atm). 3. **Scintillation Counter:** - Detects flash or scintillation of light produced when a charged particle/X-ray/gamma ray strikes a fluorescent screen. - Photons produced are amplified by dynodes and collected as an output pulse. - Output pulse is directly proportional to radiation intensity. ### Radioisotopes - **Definition:** Atoms with an unstable nucleus (unstable combination of neutrons and protons). - Emit radiations to become stable. - Same number of protons but varies in neutrons. #### Types 1. **Stable Radioisotopes:** Do not emit radiations (e.g., $^{12}C, ^{13}C, ^1H, ^2H$). 2. **Radioactive Radioisotopes:** Naturally or artificially produced unstable isotopes that emit radiations to lose energy (radioactivity). #### Study of Radioisotopes 1. **Carbon:** Three isotopes: - $^{12}C$ (stable, 6 protons, 6 neutrons) - $^{13}C$ (stable, 6 protons, 7 neutrons) - $^{14}C$ (unstable, 6 protons, 8 neutrons), decays to $^{14}N + \beta^-$. 2. **Iodine:** Two isotopes: - Iodine-127 (stable, 53 protons, 74 neutrons) - Iodine-131 (unstable, 53 protons, 78 neutrons) 3. **Phosphorus:** Two isotopes: - Phosphorus-31 (stable) - Phosphorus-32 (unstable) ### Production of Isotopes/Radioisotopes 1. **Reactor Nuclear Irradiation:** - Fissionable material (Uranium) in a moderator slows down fast neutrons. - Example: $$^{59}Co + n \rightarrow ^{60}Co + \gamma$$ 2. **Cyclotrons:** - High energy charged particles bombard stable nuclei. - Radionuclides decompose by positron emission or electron capture. - Example: $$^{24}Mg + ^2H \rightarrow ^{22}Na + ^4He$$ ### Applications of Radioisotopes #### Diagnostic Applications - Used for diagnosis (X-rays). - **Heart:** Thallium Tl-201 chloride injection for myocardial imaging. - **Thyroid:** Iodine I-131 (sodium iodide) for thyroid scanning. #### Therapeutic Applications - Destructive features of radiations destroy abnormally multiplied cells, inhibiting new cell/tissue formation. - Used in cancer treatment involving cellular malfunction. ### Sodium Iodide I-131 - **Definition:** Radiopharmaceutical used to treat malignant thyroid. - Ionizing radiations damage thyroid tissue. - Emits 90% $\beta$-radiations and 10% $\gamma$-radiation. #### Mechanism - Iodide enters thyroid via sodium/iodide symporter, accumulates, oxidizes into iodine, and emits radiations. - $\beta$-radiations destroy thyroid tissue. #### Properties - Colorless solution, pH 7-10. - Half-life of I-131 is 8.4 days. - Emits $\beta$- and $\gamma$-radiations. #### Uses - Treatment of hyperthyroidism. - Some cases of thyroid malignancy. ### Precautions and Storage of Radiopharmaceuticals #### Precautions in Handling - Handle with care to protect personnel. - Do not touch radioactive emitter directly; use forceps or appropriate instruments. - Use rubber gloves for liquid radioactive materials. - Do not contaminate working areas. - Avoid smoking, eating, drinking in laboratories where radioactive materials are handled. - Use protective clothing and shielding. - Radioactive substances used within a short period. - Dispose of radioactive material with great care. #### Storage - Stored in airtight, shielded, labeled containers. - Storage areas monitored per national/international regulations. - Containers may darken due to irradiation; optimum storage conditions maintained. - All requirements prescribed by the Department of Atomic Energy (DAE) for radioisotope facilities in hospitals/pharmacies.