D. Pharmacy 1st Year — Pharmaceutical Chemistry (ER-20-12T)
PART - I (Attempt any SIX — 6×5 = 30)
a. Importance of Limit Tests + Principle & Procedure of Limit Test for Chlorides
Importance of Limit Tests:
Limit tests are quantitative or semi-quantitative tests used to check that impurities in a drug do not exceed the permissible (safe) limit as specified by the pharmacopoeia. They ensure drug safety, purity, and quality. They do not identify the impurity but confirm it is within acceptable limits.
Principle of Limit Test for Chlorides:
When chloride ions (Cl⁻) react with silver nitrate (AgNO₃) in the presence of dilute nitric acid, a white opalescent turbidity of silver chloride (AgCl) is produced. The turbidity of the test solution is compared visually with a standard chloride solution (containing a known amount of NaCl) treated identically.
Cl⁻ + AgNO₃ → AgCl↓ (white turbidity) + NO₃⁻
Procedure:
- Dissolve the specified weight of the substance in water in a Nessler cylinder (50 mL).
- Add 1 mL of dilute nitric acid and 1 mL of AgNO₃ solution (2% w/v).
- Make up to 50 mL with water. Mix and allow to stand for 5 minutes.
- Prepare a standard: take the specified volume of standard chloride solution (containing 5 µg Cl⁻/mL), add the same reagents in the same quantities.
- Compare turbidity: the test solution should not be more turbid than the standard.
b. Acid–Base Titration with Indicators
Acid–Base Titration:
A volumetric method in which a standard solution of an acid (or base) is used to determine the concentration of a base (or acid) by neutralisation reaction until the equivalence point is reached.
Acid + Base → Salt + Water
Examples:
- HCl + NaOH → NaCl + H₂O (strong acid vs. strong base)
- CH₃COOH + NaOH → CH₃COONa + H₂O (weak acid vs. strong base)
Indicators Used in Acid–Base Titration:
| Indicator | pH Range | Colour Change | Used For |
|---|
| Phenolphthalein | 8.3 – 10.0 | Colourless → Pink | Weak acid vs. strong base |
| Methyl orange | 3.1 – 4.4 | Red → Yellow | Strong acid vs. weak base |
| Methyl red | 4.4 – 6.2 | Red → Yellow | Strong acid vs. weak base |
| Litmus | 6.0 – 8.0 | Red → Blue | General |
An ideal indicator changes colour sharply at the equivalence point of the titration.
c. Classification, Preparation and Uses of Haematinics
Definition: Haematinics are drugs that supply essential factors required for the formation of red blood cells (erythropoiesis).
Classification:
- Iron preparations — for iron-deficiency anaemia
- Ferrous sulphate, Ferrous gluconate, Ferric ammonium citrate
- Vitamin B₁₂ — for megaloblastic/pernicious anaemia
- Cyanocobalamin, Hydroxocobalamin
- Folic acid — for megaloblastic anaemia
- Erythropoietin — for anaemia of chronic renal failure
Preparation of Ferrous Sulphate (FeSO₄·7H₂O):
- Iron is dissolved in dilute sulphuric acid
- The resulting solution is concentrated and crystallised
- Blue-green crystals are obtained
Uses:
- Treatment of iron-deficiency anaemia
- Prophylaxis in pregnancy, infancy, and growing children
- Vitamin B₁₂ — pernicious anaemia, subacute combined degeneration of spinal cord
- Folic acid — neural tube defect prevention in pregnancy
d. Nomenclature of Heterocyclic Compounds (up to Three Rings)
Heterocyclic compounds contain one or more heteroatoms (N, O, S) in the ring.
Rules of Nomenclature (Hantzsch-Widman System):
- Ring size is indicated by a prefix; heteroatom by a specific prefix
- Nitrogen → aza, Oxygen → oxa, Sulphur → thia
- Unsaturation is indicated by -ene or absence of -ane
Common Prefixes for Ring Size:
| Ring atoms | Unsaturated | Saturated |
|---|
| 3 | -irene | -irane |
| 4 | -ete | -etane |
| 5 | -ole | -olane |
| 6 | -ine | -ane |
Examples:
- Pyrrole — 5-membered ring with 1 N (azole)
- Furan — 5-membered ring with 1 O (oxole)
- Thiophene — 5-membered ring with 1 S (thiole)
- Pyridine — 6-membered ring with 1 N
- Quinoline — bicyclic: benzene fused with pyridine (2 rings)
- Acridine — tricyclic: benzene + pyridine + benzene (3 rings)
- Indole — bicyclic: benzene + pyrrole
- Purine — bicyclic: pyrimidine + imidazole (important in nucleotides)
e. Classification of Drugs Acting on CNS + Two Sedatives and Hypnotics
Classification of CNS Drugs:
-
CNS Depressants
- General anaesthetics (ether, halothane)
- Sedatives & hypnotics (barbiturates, benzodiazepines)
- Anxiolytics (diazepam)
- Antipsychotics (chlorpromazine)
- Antidepressants (amitriptyline)
- Opioid analgesics (morphine)
- Antiepileptics (phenytoin)
-
CNS Stimulants
- Amphetamine, caffeine, methylphenidate
-
Drugs acting on autonomic nervous system (indirectly affecting CNS)
Two Sedatives and Hypnotics:
1. Phenobarbitone (Phenobarbital) — Barbiturate
- Mechanism: Enhances GABA-A receptor activity → prolongs Cl⁻ channel opening
- Uses: Sedation, epilepsy, insomnia (now less common)
- Low dose = sedative; high dose = hypnotic
2. Diazepam — Benzodiazepine
- Mechanism: Binds GABA-A receptor at benzodiazepine site → increases frequency of Cl⁻ channel opening
- Uses: Anxiety, insomnia, muscle relaxation, status epilepticus, alcohol withdrawal
- Safer therapeutic index than barbiturates
f. Sympathomimetic Agents — Classification and Examples
Definition: Drugs that mimic the effects of sympathetic nervous system stimulation (adrenergic effects).
Classification:
A. Based on receptor selectivity:
| Type | Example |
|---|
| α₁ + α₂ agonist | Noradrenaline, Phenylephrine |
| β₁ + β₂ agonist | Isoprenaline |
| α + β agonist | Adrenaline (Epinephrine) |
| β₂ selective | Salbutamol, Terbutaline |
| α₁ selective | Phenylephrine |
| Dopamine agonist | Dopamine |
B. Based on mechanism:
- Direct-acting — act directly on adrenoceptors: Adrenaline, Noradrenaline, Salbutamol
- Indirect-acting — release noradrenaline from nerve terminals: Amphetamine, Tyramine
- Mixed-acting — both mechanisms: Ephedrine, Pseudoephedrine
Uses:
- Anaphylaxis (Adrenaline)
- Bronchial asthma (Salbutamol)
- Nasal decongestant (Xylometazoline)
- Hypotension/shock (Noradrenaline, Dopamine)
- Cardiac arrest (Adrenaline)
g. Anti-arrhythmic Drugs — Classification and Uses
Arrhythmia: Abnormal heart rhythm due to disturbances in impulse generation or conduction.
Classification (Vaughan Williams):
| Class | Mechanism | Examples | Uses |
|---|
| IA | Na⁺ channel block (intermediate) | Quinidine, Procainamide, Disopyramide | AF, VT, SVT |
| IB | Na⁺ channel block (fast off) | Lignocaine, Mexiletine | VT, VF (post-MI) |
| IC | Na⁺ channel block (slow off) | Flecainide, Propafenone | SVT, AF |
| II | Beta-blockers | Propranolol, Atenolol | AF, SVT, post-MI |
| III | K⁺ channel block → prolong repolarisation | Amiodarone, Sotalol | AF, VT, VF |
| IV | Ca²⁺ channel block | Verapamil, Diltiazem | SVT, AF rate control |
Uses:
- SVT (supraventricular tachycardia): Verapamil, Adenosine
- Atrial fibrillation: Amiodarone, Digoxin
- Ventricular tachycardia/fibrillation: Lignocaine, Amiodarone
- Post-MI prophylaxis: Propranolol
PART - II (Attempt any TEN — 10×3 = 30)
i. Accuracy and Precision
Accuracy: The closeness of a measured value to the true or accepted value.
- Example: If the true value of a drug content is 100 mg and the test gives 99.8 mg → high accuracy.
Precision: The closeness of repeated measurements to each other (reproducibility), regardless of the true value.
- Example: If repeated tests give 98.1, 98.2, 98.0 mg consistently → high precision (but may not be accurate).
A method can be precise without being accurate, but a truly accurate method must also be precise.
Expressed as:
- Accuracy → % error = [(measured − true)/true] × 100
- Precision → Relative Standard Deviation (RSD) or Coefficient of Variation (CV)
ii. Volumetric Analysis — Definition and Advantages
Definition: Volumetric (titrimetric) analysis is a quantitative analytical method in which the volume of a standard solution (titrant) required to react completely with a measured volume or weight of the substance under test (analyte) is measured to determine the concentration/amount of that substance.
Advantages:
- Simple, rapid, and inexpensive
- Suitable for routine quality control in pharmaceutical labs
- High accuracy and precision
- Can be used for wide range of substances (acids, bases, oxidising agents, reducing agents, complexes)
- Requires simple apparatus
- Both organic and inorganic substances can be analysed
iii. Limit Test for Sulphates
Principle: Sulphate ions (SO₄²⁻) react with barium chloride (BaCl₂) in the presence of dilute hydrochloric acid to form a white turbidity of barium sulphate (BaSO₄).
SO₄²⁻ + BaCl₂ → BaSO₄↓ (white turbidity) + 2Cl⁻
Procedure:
- Dissolve the substance in water in a Nessler cylinder.
- Add 2 mL of dilute HCl and 2 mL of BaCl₂ solution (25% w/v).
- Make up to 50 mL. Allow to stand 10 minutes.
- Prepare standard: a specified volume of standard sulphate solution + same reagents.
- Compare: turbidity of test should not exceed standard.
Standard: 1 mL of 0.1816% w/v K₂SO₄ solution = 0.1 mg SO₄²⁻
iv. Complexometric Titration
Definition: A type of volumetric analysis in which complex formation between a metal ion and a ligand (complexing agent) is used to determine the concentration of the metal ion.
Most common reagent: EDTA (Ethylenediaminetetraacetic acid / Disodium edetate) — a hexadentate ligand that forms stable 1:1 complexes with most metal ions.
Example:
Ca²⁺ + EDTA → [Ca-EDTA] complex
Used to determine calcium and magnesium in water hardness tests.
Indicator: Eriochrome Black T (EBT) — turns wine-red with metal ions; at endpoint, turns blue as EDTA displaces indicator.
Uses in pharmacy: Assay of calcium gluconate, zinc sulphate, aluminium hydroxide.
v. Short Note on Antacids
Definition: Antacids are weak bases that neutralise excess hydrochloric acid in the stomach, raising gastric pH and relieving acidity symptoms.
Classification & Examples:
| Type | Examples |
|---|
| Systemic (absorbable) | Sodium bicarbonate (NaHCO₃) |
| Non-systemic (non-absorbable) | Al(OH)₃, Mg(OH)₂, Calcium carbonate |
| Combination | Magaldrate, Gelusil (Al(OH)₃ + Mg(OH)₂) |
Mechanism: Neutralise HCl → raise pH above 4 → relieve pain, reduce pepsin activity
Uses: Peptic ulcer, gastritis, GERD (gastroesophageal reflux disease), heartburn
Side effects:
- Al(OH)₃ → constipation
- Mg(OH)₂ → diarrhoea
- NaHCO₃ → systemic alkalosis, CO₂ belching
vi. Cathartics — Definition and Two Examples
Definition: Cathartics (laxatives/purgatives) are drugs that promote and accelerate bowel movements (defaecation) by stimulating intestinal motility or increasing stool bulk/water content.
Classification:
- Bulk-forming: Isabgol, Methylcellulose
- Osmotic/Saline: Magnesium sulphate, Lactulose
- Stimulant/Irritant: Castor oil, Senna, Bisacodyl
- Lubricant: Liquid paraffin
- Stool softeners: Docusate sodium
Two Examples:
- Magnesium sulphate (Epsom salt): Osmotic cathartic; retains water in gut by osmosis → increases peristalsis.
- Castor oil: Stimulant cathartic; converted to ricinoleic acid in intestine → irritates mucosa → increased peristalsis.
Uses: Constipation, before surgery/radiological examination, poisoning (to expel toxins).
vii. Dental Products — Definition and Examples
Dental products are pharmaceutical preparations used to maintain oral hygiene, treat dental diseases, and protect teeth and gums.
Classification with Examples:
| Category | Examples |
|---|
| Dentifrices (toothpastes/powders) | Calcium carbonate, Sodium lauryl sulphate, Fluoride (NaF) |
| Mouth washes/antiseptics | Chlorhexidine gluconate, Hydrogen peroxide, Thymol |
| Desensitising agents | Potassium nitrate, Strontium chloride |
| Topical fluorides | Sodium fluoride (NaF), Stannous fluoride (SnF₂) |
| Dental anaesthetics | Lignocaine gel, Benzocaine |
| Anticaries agents | Sodium fluoride — hardens enamel by forming fluorapatite |
Uses: Prevention of dental caries, treatment of gingivitis, tooth sensitivity, oral infections.
viii. Beta-blockers — Two Examples
Beta-blockers (β-adrenergic antagonists): Drugs that competitively block β-adrenergic receptors, reducing the effects of catecholamines (adrenaline, noradrenaline).
Classification:
- Non-selective (β₁ + β₂): Propranolol, Sotalol
- Cardioselective (β₁): Atenolol, Metoprolol, Bisoprolol
- With intrinsic sympathomimetic activity: Pindolol
Two Examples:
- Propranolol — non-selective β-blocker; used in hypertension, angina, arrhythmias, thyrotoxicosis, migraine prophylaxis
- Atenolol — cardioselective β₁-blocker; used in hypertension, angina, post-MI
Mechanism: Block β receptors → decrease heart rate, force of contraction, renin release → lower BP and O₂ demand.
ix. Hypoglycemic Agents
Definition: Drugs used to lower elevated blood glucose levels in diabetes mellitus.
Classification:
| Class | Mechanism | Examples |
|---|
| Sulphonylureas | Stimulate insulin secretion from β-cells | Glibenclamide, Glipizide, Glimepiride |
| Biguanides | Decrease hepatic glucose output; increase peripheral uptake | Metformin |
| Thiazolidinediones | Activate PPAR-γ → insulin sensitisation | Pioglitazone, Rosiglitazone |
| Alpha-glucosidase inhibitors | Delay carbohydrate absorption | Acarbose |
| DPP-4 inhibitors | Increase incretin levels | Sitagliptin, Vildagliptin |
| SGLT-2 inhibitors | Increase urinary glucose excretion | Dapagliflozin, Empagliflozin |
| Insulin | Replaces deficient endogenous insulin | Regular, NPH, Glargine |
Uses: Type 2 diabetes mellitus (oral agents); Type 1 diabetes mellitus (insulin).
x. Classification of Anti-infective Agents
Anti-infective agents are drugs that destroy or inhibit the growth of microorganisms causing infections.
Classification:
Anti-infective Agents
├── Antibacterials
│ ├── Antibiotics (Penicillin, Streptomycin, Tetracycline)
│ └── Sulfonamides (Sulfadiazine, Co-trimoxazole)
├── Antifungals
│ ├── Polyenes (Amphotericin B, Nystatin)
│ ├── Azoles (Fluconazole, Clotrimazole)
│ └── Allylamines (Terbinafine)
├── Antivirals
│ ├── Nucleoside analogues (Acyclovir, Zidovudine)
│ └── Protease inhibitors (Ritonavir, Lopinavir)
├── Antiprotozoals
│ ├── Antimalarials (Chloroquine, Quinine)
│ └── Antiamoebics (Metronidazole)
├── Anthelmintics (Albendazole, Mebendazole)
└── Antitubercular (Isoniazid, Rifampicin, Pyrazinamide)
xi. Sulfonamides — Definition and Two Examples
Definition: Sulfonamides are synthetic bacteriostatic anti-infective agents that structurally resemble para-aminobenzoic acid (PABA) and competitively inhibit the enzyme dihydropteroate synthase, blocking folic acid synthesis in bacteria.
Bacteria cannot absorb exogenous folate → folic acid synthesis is essential → sulfonamides selectively inhibit bacteria (human cells use preformed folate from diet).
Mechanism:
PABA → (blocked by sulfonamide) → dihydropteroic acid → dihydrofolic acid → tetrahydrofolic acid (essential for DNA synthesis)
Two Examples:
-
Sulfadiazine
- Uses: Urinary tract infections, burns (silver sulfadiazine), toxoplasmosis, meningococcal meningitis prophylaxis
-
Sulfamethoxazole (combined with Trimethoprim as Co-trimoxazole)
- Uses: UTI, respiratory tract infections, Pneumocystis jirovecii pneumonia (PCP), typhoid
Side effects: Crystalluria (drink plenty of water), hypersensitivity, Stevens-Johnson syndrome, bone marrow suppression.