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UNIT-VII — Cathartics, Electrolyte Replenishers
① Very Short Answer Type [2 Marks each]
(i) Write different types of Cathartics.
Cathartics (Laxatives) promote evacuation of the bowel. Classification:
| Type | Mechanism | Examples |
|---|
| Bulk-forming | Absorb water, increase stool bulk | Ispaghula (Psyllium), Methylcellulose, Bran |
| Saline (Osmotic) cathartics | Osmotic water retention → peristalsis | Magnesium Sulphate, Magnesium Hydroxide, Magnesium Citrate, Sodium Phosphate |
| Stimulant / Irritant | Stimulate intestinal motility directly | Castor oil, Bisacodyl, Senna, Cascara |
| Surfactant / Emollient | Soften stool by emulsification | Docusate sodium (DOSS), Liquid paraffin |
| Osmotic non-saline | Retain water osmotically | Lactulose, PEG (Polyethylene glycol), Sorbitol |
| Lubricant | Lubricate intestinal wall | Liquid paraffin (Mineral oil) |
(ii) Define Saline Cathartics with examples.
Saline cathartics are salts containing magnesium cations or phosphate anions that act primarily by osmotic water retention in the intestinal lumen, increasing stool water content and stimulating peristalsis.
Mechanism: They are poorly absorbed → retain water osmotically in the gut → distend the bowel → stimulate peristalsis. Magnesium salts also stimulate CCK (cholecystokinin) release, further increasing fluid and electrolyte secretion.
Examples:
- Magnesium Sulphate (Epsom salt) — most commonly used
- Magnesium Hydroxide (Milk of Magnesia)
- Magnesium Citrate
- Sodium Phosphate
- Sodium Sulphate (Glauber's salt)
(iii) Define Extra and Intracellular Electrolytes with examples.
| Type | Location | Normal Concentration | Examples |
|---|
| Extracellular Electrolytes | Outside the cell (plasma, interstitial fluid) | Na⁺ ~142 mEq/L; Cl⁻ ~103 mEq/L; HCO₃⁻ ~26 mEq/L | Na⁺, Cl⁻, HCO₃⁻, Ca²⁺, Mg²⁺ |
| Intracellular Electrolytes | Inside the cell (cytoplasm) | K⁺ ~150 mEq/L; Mg²⁺ ~40 mEq/L; PO₄³⁻ ~150 mEq/L | K⁺, Mg²⁺, HPO₄²⁻, proteins, SO₄²⁻ |
The Na⁺/K⁺-ATPase pump maintains this gradient, pumping 3 Na⁺ out and 2 K⁺ in per cycle.
(iv) What is Electrolyte Combination Therapy?
Electrolyte combination therapy involves the simultaneous administration of two or more electrolytes to restore the body's fluid and electrolyte balance. Used when there are multiple deficits.
Examples:
- ORS (Oral Rehydration Solution): Na⁺ + K⁺ + Cl⁻ + HCO₃⁻/citrate + glucose
- Ringer's Lactate (Hartmann's solution): Na⁺ + K⁺ + Ca²⁺ + Cl⁻ + lactate
- Normal Saline: NaCl 0.9%
- Darrow's solution: Na⁺ + K⁺ + Cl⁻ + lactate (used in severe dehydration with hyponatraemia)
Rationale: corrects dehydration, acidosis, and electrolyte imbalances simultaneously; no single salt can address multiple deficits.
(v) What is the full form of ORS?
ORS = Oral Rehydration Solution (also: Oral Rehydration Salts)
Developed by WHO and UNICEF; used primarily in the treatment of acute dehydrating diarrhoea and cholera.
(vi) What are OTT agents?
OTT (Over-The-Counter) agents are pharmaceutical products that can be purchased without a prescription. In the context of GI pharmacology:
Examples relevant to this unit:
- Magnesium hydroxide (Milk of Magnesia) — OTC laxative/antacid
- Calcium carbonate (Tums) — OTC antacid
- PEG 3350 (Miralax) — OTC osmotic laxative
- Sodium bicarbonate (Alka Seltzer) — OTC antacid/effervescent
OTT agents must be: safe at therapeutic doses, self-diagnosable conditions, low potential for abuse, appropriate labelling.
(vii) What are the uses of Aluminium Hydroxide Gel?
- Antacid — treatment of peptic ulcer, GERD, gastritis, hyperacidity
- Phosphate binder — in chronic kidney disease (CKD) to reduce hyperphosphataemia
- Adsorbs pepsin — reduces proteolytic mucosal damage
- Mucosal protective agent — forms a gel coat over ulcer base
- Adjuvant in vaccines — aluminium hydroxide gel used as an immunological adjuvant (alum)
- Treatment of fluoride poisoning — binds fluoride ions in GI tract
(viii) What are major physiological ions?
| Ion | Location | Normal Level |
|---|
| Sodium (Na⁺) | Extracellular | 135–145 mEq/L |
| Potassium (K⁺) | Intracellular | 3.5–5.0 mEq/L (plasma) |
| Calcium (Ca²⁺) | Extracellular/bone | 8.5–10.5 mg/dL |
| Magnesium (Mg²⁺) | Intracellular | 1.5–2.5 mEq/L |
| Chloride (Cl⁻) | Extracellular | 96–106 mEq/L |
| Bicarbonate (HCO₃⁻) | Extracellular | 22–28 mEq/L |
| Phosphate (HPO₄²⁻) | Intracellular | 2.5–4.5 mg/dL (plasma) |
(ix) Name the natural buffer systems in the human body.
- Bicarbonate–Carbonic Acid Buffer (most important ECF buffer): HCO₃⁻/H₂CO₃ — pKₐ 6.1; effective for metabolic disturbances
- Phosphate Buffer: HPO₄²⁻/H₂PO₄⁻ — important in urine and intracellular fluid
- Protein Buffer (intracellular): Plasma proteins (albumin), intracellular proteins — major ICF buffer
- Haemoglobin Buffer: Most effective buffer against both respiratory (CO₂) and metabolic acids; works via imidazole groups of histidine
- Ammonia Buffer System (renal): NH₃ + H⁺ → NH₄⁺ — important in urine acidification
(x) What is the role of Sodium, Calcium, Chloride, and Bicarbonate ions?
Sodium (Na⁺):
- Maintains ECF osmolality and volume
- Essential for nerve impulse transmission (action potential)
- Drives Na⁺/K⁺-ATPase pump
- Controls water distribution between compartments
Calcium (Ca²⁺):
- Bone and teeth mineralization (99% in skeleton)
- Muscle contraction (troponin C binding)
- Neurotransmitter release
- Blood coagulation (Factor IV)
- Second messenger in cell signalling
- Cardiac conduction
Chloride (Cl⁻):
- Principal anion of ECF; maintains electroneutrality
- Component of gastric HCl (digestion)
- Chloride shift in RBCs during CO₂ transport
- Regulates osmotic pressure alongside Na⁺
Bicarbonate (HCO₃⁻):
- Primary buffer of blood (normal: 22–28 mEq/L)
- Transports CO₂ from tissues to lungs (CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻)
- Regulated by kidneys to maintain pH 7.35–7.45
- Alkalinizes urine
② Long Answer Type [10 Marks each]
(i) Explain the mechanism of maintenance of physiological acid-base balance. Write a note on the biochemical and biological role of Na⁺ and HCO₃⁻ ions.
Physiological Acid-Base Balance
The body maintains blood pH between 7.35–7.45 (arterial = 7.40) through three integrated mechanisms:
A. Buffer Systems (Immediate — seconds)
-
Bicarbonate Buffer (most important ECF buffer):
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ (catalysed by carbonic anhydrase)
- pH = pKₐ + log([HCO₃⁻] / [H₂CO₃]) = 6.1 + log(20/1) = 7.40
- Normal ratio HCO₃⁻ : H₂CO₃ = 20:1 (must be maintained)
- Effective against metabolic disturbances; not effective for respiratory disturbances (cannot buffer H₂CO₃)
-
Haemoglobin Buffer:
- Buffers both CO₂ (respiratory) and noncarbonic (metabolic) acids
- Deoxyhaemoglobin is a better buffer than oxyhaemoglobin
- Imidazole groups of histidine residues accept H⁺
-
Plasma Protein Buffer: albumin and globulins have free -NH₂ and -COOH groups
-
Phosphate Buffer (intracellular/urine):
HPO₄²⁻ + H⁺ ↔ H₂PO₄⁻ (pKₐ 6.8 — ideal for intracellular pH ~7.0)
B. Respiratory Compensation (minutes to hours)
- Medullary chemoreceptors detect changes in PaCO₂ and pH
- Acidosis: ↑ ventilation → blows off more CO₂ → raises pH
- Alkalosis: ↓ ventilation → CO₂ retained → lowers pH
- Relationship: PaCO₂ rises ~0.25–1 mmHg for each 1 mEq/L rise in HCO₃⁻
C. Renal Compensation (hours to days — most powerful)
- Reabsorption of HCO₃⁻ — primarily in proximal tubule; enhanced in acidosis
- Excretion of titratable acids — H₂PO₄⁻ in distal tubule
- Ammonia production (ammoniagenesis):
Glutamine → NH₃ + glutamate (in tubular cells)
NH₃ + H⁺ → NH₄⁺ (secreted into urine)
Acid-Base Disorders:
| Disorder | pH | PaCO₂ | HCO₃⁻ | Compensation |
|---|
| Metabolic acidosis | ↓ | ↓ (resp. compensation) | ↓ (primary) | Hyperventilation |
| Metabolic alkalosis | ↑ | ↑ (resp. compensation) | ↑ (primary) | Hypoventilation |
| Respiratory acidosis | ↓ | ↑ (primary) | ↑ (renal comp.) | ↑ HCO₃⁻ reabsorption |
| Respiratory alkalosis | ↑ | ↓ (primary) | ↓ (renal comp.) | ↓ HCO₃⁻ reabsorption |
Role of Na⁺:
| Function | Detail |
|---|
| ECF osmolality | Na⁺ is the primary determinant of plasma osmolality (~280–295 mOsm/kg); controls water distribution |
| ECF volume | Total body Na⁺ determines ECF volume; regulated by renin-angiotensin-aldosterone system (RAAS) |
| Resting membrane potential | High extracellular Na⁺ maintains negative resting potential (−70 mV) |
| Action potential | Rapid Na⁺ influx during depolarization of nerve and muscle |
| Na⁺/K⁺-ATPase pump | 3 Na⁺ pumped out + 2 K⁺ in per cycle; maintains gradients for cell function |
| Glucose/amino acid co-transport | SGLT1 uses Na⁺ gradient to absorb glucose in gut and kidneys |
| Acid-base | Na⁺ is a strong cation; contributes to strong ion difference (SID), indirectly affecting pH |
Role of HCO₃⁻:
| Function | Detail |
|---|
| Primary blood buffer | Normal level 22–28 mEq/L; neutralizes metabolic acids |
| CO₂ transport | 70% of CO₂ carried as HCO₃⁻ in plasma after chloride shift |
| Renal acid-base regulation | Kidneys reabsorb or excrete HCO₃⁻ to correct pH imbalances |
| Pancreatic secretion | Pancreatic juice is rich in HCO₃⁻; neutralizes gastric acid in duodenum |
| Intestinal fluid | Component of intestinal secretions; lost in diarrhoea → metabolic acidosis |
| Urinary alkalinization | HCO₃⁻ excretion alkalinizes urine; used therapeutically in UTI, urate nephropathy |
(ii) List major intra- and extracellular electrolytes. Explain the preparation and uses of Dextrose and Sodium Chloride Injection.
Major Electrolytes:
Extracellular (mEq/L): Na⁺ 142, Cl⁻ 103, HCO₃⁻ 26, Ca²⁺ 5, Mg²⁺ 2, K⁺ 4
Intracellular (mEq/L): K⁺ 150, Mg²⁺ 40, HPO₄²⁻ 150, Proteins 65, Na⁺ 10
Sodium Chloride Injection (Normal Saline)
Official Name: Sodium Chloride Injection IP/BP
Composition: 0.9% w/v NaCl in Water for Injection = isotonic (~308 mOsm/L)
Preparation:
- Dissolve 9 g NaCl in sufficient Water for Injection (WFI)
- Make up volume to 1000 mL
- Adjust pH to 4.5–7.0 (IP)
- Filter through 0.22 µm membrane
- Fill into sealed glass ampoules or infusion bags
- Sterilize by autoclaving (121°C, 15 min) or by aseptic filtration
Other available concentrations:
- 0.45% NaCl (hypotonic — "half-normal")
- 3% NaCl (hypertonic — for severe hyponatraemia)
Assay (IP): Mohr's method — argentometric titration with silver nitrate, potassium chromate indicator. Each mL of 0.1 M AgNO₃ = 5.844 mg NaCl. IP requirement: 95–105% of stated amount.
Medicinal Uses:
- ECF volume replacement in dehydration, shock, haemorrhage
- Hyponatraemia (0.9% or 3% NaCl)
- Vehicle for IV drug administration
- Wound irrigation and eye drops (0.9%)
- Nasal saline spray (congestion)
- Emergency resuscitation
Adverse Effects: Hypernatraemia, hyperchloraemic metabolic acidosis (with large volumes of 0.9% NaCl), fluid overload in cardiac/renal disease
Dextrose Injection (Glucose Injection)
Official Name: Dextrose Injection IP / Glucose Intravenous Infusion BP
Composition: D-Glucose (anhydrous or monohydrate) in Water for Injection
Available Concentrations:
- 5% w/v — isotonic (~278 mOsm/L)
- 10%, 25%, 50% — hypertonic
Preparation:
- Dissolve anhydrous dextrose in WFI
- Adjust pH to 3.5–6.5 (IP) — slightly acidic to prevent caramelisation during sterilisation
- Filter and fill into sealed containers
- Sterilize by autoclaving (121°C, 15 min)
Assay (IP): Optical rotation (polarimetry) — dextrose is dextrorotatory (+52.7°); OR enzymatic glucose oxidase method
Medicinal Uses:
- Caloric (energy) source — 5% dextrose provides 200 kcal/L; used in starvation, pre/post-operatively
- Hypoglycaemia — 25–50% dextrose IV (emergency)
- Vehicle for IV drugs and electrolytes
- Hyperkalaemia — glucose + insulin drives K⁺ into cells
- Cerebral oedema — 20% mannitol (osmotic); hypertonic dextrose (adjunct)
- Hepatic failure — provides energy while sparing protein catabolism
Note: 5% dextrose is isotonic but distributes throughout total body water (not ECF-specific like NaCl) — water of distribution after glucose is metabolized.
(iii) Name the major physiological ions and write their role. Add a note on physiological acid-base balance.
(See Very Short Answer (viii) and (x) above for ionic roles; see Long Answer (i) for acid-base balance detail)
Summary Table of Roles:
| Ion | Key Roles |
|---|
| Na⁺ | ECF osmolality, action potential, Na/K pump, co-transport |
| K⁺ | Resting membrane potential, intracellular osmolality, cardiac rhythm, enzyme cofactor |
| Ca²⁺ | Muscle contraction, coagulation, bone, neurotransmission, cell signalling |
| Mg²⁺ | Enzyme cofactor (>300 reactions), ATP stabilisation, neuromuscular transmission |
| Cl⁻ | ECF anion balance, gastric acid, chloride shift in CO₂ transport |
| HCO₃⁻ | Acid-base buffer, CO₂ transport, pancreatic secretion |
| HPO₄²⁻ | Intracellular buffer, ATP/ADP energy, bone mineralisation, nucleic acids |
(iv) Define Cathartics. Give the preparation and assay of Magnesium Sulphate.
Definition:
Cathartics (purgatives) are agents that promote rapid, complete evacuation of the bowel, usually producing a fluid or watery stool. They differ from laxatives in degree of action — cathartics produce a more intense, faster purging effect.
Magnesium Sulphate (Epsom Salt)
Chemical Name: Magnesium Sulphate Heptahydrate
Formula: MgSO₄·7H₂O | MW: 246.47
Synonyms: Epsom salt, Bitter salt
Chemical Properties:
- Colourless, efflorescent crystals or white granular powder
- Bitter saline taste
- Freely soluble in water; practically insoluble in alcohol
- Loses water of crystallisation on heating
Preparation (Industrial/IP):
Method 1 — From Magnesite (MgCO₃):
MgCO₃ + H₂SO₄ → MgSO₄ + H₂O + CO₂
- Solution evaporated and crystallised to obtain MgSO₄·7H₂O
Method 2 — From Dolomite:
- Dolomite (CaMg(CO₃)₂) reacted with H₂SO₄
- CaSO₄ precipitates out; MgSO₄ remains in solution
- Concentrated and crystallised
Method 3 — From Magnesium Hydroxide:
Mg(OH)₂ + H₂SO₄ → MgSO₄ + 2H₂O
- Crystallised as heptahydrate by cooling
Assay (IP):
Complexometric Titration with EDTA:
- Dissolve accurately weighed sample (~0.2 g) in water
- Add ammonia buffer (pH 10)
- Add indicator: Eriochrome Black T (EBT) (solution turns wine-red)
- Titrate with 0.05 M disodium EDTA until colour changes from wine-red to pure blue
MgSO₄ + EDTA (Na₂H₂Y) → [Mg-EDTA]²⁻ complex + 2H⁺
Calculation: 1 mL of 0.05 M EDTA = 12.32 mg MgSO₄ (anhydrous) or 6.017 mg Mg
IP requirement: Contains not less than 99.0% and not more than 100.5% MgSO₄·7H₂O
Medicinal Uses of Magnesium Sulphate:
| Use | Details |
|---|
| Saline cathartic/purgative | 5–15 g orally in water; produces watery evacuation in 1–3 hours |
| Anticonvulsant | IV/IM in eclampsia and pre-eclampsia of pregnancy; 4 g IV loading dose |
| Antidote | For barium poisoning (BaSO₄ precipitated) |
| Electrolyte replenisher | IV MgSO₄ in severe hypomagnesaemia |
| Anti-arrhythmic | For torsades de pointes, digoxin toxicity |
| Bronchodilator (adjunct) | IV in severe asthma refractory to β₂-agonists |
| Neuroprotection | In premature labour to protect fetal brain |
| Externally | Hot Epsom salt soaks for muscle soreness, inflammatory conditions |
Adverse Effects: Hypermagnesaemia with overdose → loss of DTRs, respiratory depression, cardiac arrest. Antidote: IV Calcium Gluconate.
③ Short Answer Type [5 Marks each]
① Write a note on Physiological Acid-Base Balance.
(Covered in detail in Long Answer (i) above — buffer systems, respiratory and renal compensation, Henderson-Hasselbalch equation)
Key equation:
pH = 6.1 + log( [HCO₃⁻] / 0.0307 × PaCO₂ )
Normal values: pH 7.40; PaCO₂ 40 mmHg; HCO₃⁻ 24 mEq/L
② Describe the important functions of Bicarbonate and Sodium ions in the body.
(See Very Short Answer (x) above and Long Answer (i) — covered in full detail)
③ Write a note on Electrolytes used in Replacement Therapy.
Electrolyte replacement therapy corrects deficits of specific ions lost through diarrhoea, vomiting, burns, renal disease, or inadequate intake.
| Electrolyte Preparation | Composition | Use |
|---|
| Normal Saline (0.9% NaCl) | Na⁺ 154, Cl⁻ 154 mEq/L | ECF volume deficit, hyponatraemia |
| Ringer's Lactate | Na⁺ 130, K⁺ 4, Ca²⁺ 3, Cl⁻ 109, Lactate 28 mEq/L | Burns, trauma, surgical fluid loss |
| ORS | Na⁺ 75, K⁺ 20, Cl⁻ 65, Citrate 10, Glucose 75 mmol/L | Diarrhoeal dehydration |
| KCl injection | Potassium 1–2 mEq/mL (diluted) | Hypokalaemia |
| Calcium Gluconate 10% | Ca²⁺ 0.45 mEq/mL | Hypocalcaemia, Mg toxicity antidote |
| Magnesium Sulphate | Mg²⁺ IV | Hypomagnesaemia, eclampsia |
| Sodium Bicarbonate 7.5% | HCO₃⁻ 0.89 mEq/mL | Metabolic acidosis, cardiac arrest |
④ Write the composition and use of ORS.
WHO-ORS (Revised Low-Osmolarity, 2003):
| Component | Amount per litre |
|---|
| Sodium chloride | 2.6 g |
| Glucose (anhydrous) | 13.5 g |
| Potassium chloride | 1.5 g |
| Trisodium citrate (dihydrate) | 2.9 g |
| Osmolarity | 245 mOsm/L |
| Sodium | 75 mmol/L |
| Potassium | 20 mmol/L |
| Chloride | 65 mmol/L |
| Citrate | 10 mmol/L |
| Glucose | 75 mmol/L |
(Older formulation had 311 mOsm/L; revised formula reduces osmolarity for better efficacy)
Mechanism: Glucose co-transports Na⁺ via SGLT1 in the intestinal mucosa, driving water absorption (glucose-coupled Na⁺ absorption is intact even in cholera/diarrhoea).
Uses:
- Treatment of acute dehydrating diarrhoea (cholera, gastroenteritis)
- Vomiting and dehydration in children
- Heat exhaustion / exercise-induced electrolyte loss
- Post-surgical fluid replacement (mild)
- Prevention and treatment of dehydration in resource-limited settings
⑤ Write a note on the Buffer Systems of the Body.
(See Long Answer (i) Section A + Very Short Answer (ix) above — covered in full detail)
The four buffer systems:
- Bicarbonate buffer — ECF, plasma (pKₐ 6.1)
- Haemoglobin buffer — RBCs (best for both respiratory and metabolic)
- Plasma protein buffer — albumin, globulins
- Phosphate buffer — ICF and urine (pKₐ 6.8)
"The bicarbonate buffer is effective against metabolic, but not respiratory, acid-base disturbances. In contrast, haemoglobin is capable of buffering both carbonic (CO₂) and noncarbonic (nonvolatile) acids." (Morgan & Mikhail's Clinical Anesthesiology)
⑥ Give the preparation and assay of Magnesium Sulphate.
(Covered in full detail in Long Answer (iv) above)
Additional 2-Mark Questions (Right Column)
⑤ What are Saline Cathartics? What is their mechanism of action?
(Covered in Very Short Answer (ii) above)
Mechanism in brief:
- Osmotic retention: Poorly absorbed Mg²⁺/SO₄²⁻ ions retain water in intestinal lumen by osmosis
- CCK stimulation: Mg²⁺ stimulates release of cholecystokinin → fluid and electrolyte secretion + enhanced intestinal motility
- Direct mucosal effect: May stimulate release of inflammatory mediators
- Result: Watery evacuation within 0.5–6 hours
⑥ Give the method of preparation, assay, medicinal use of Magnesium Sulphate with its chemical formula and synonym.
Chemical Formula: MgSO₄·7H₂O
Synonym: Epsom Salt / Bitter Salt
(Full preparation, assay, and uses covered in Long Answer (iv) above)
Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics; Morgan & Mikhail's Clinical Anesthesiology 7e; Harrison's Principles of Internal Medicine 22e; Rosen's Emergency Medicine