BDS 202 - General and Dental Pharmacology

Theory Examination July 2024-25 — Model Answers

PART A

Q.1 Classify NSAIDs. Write the uses and adverse effects of Aspirin. (2+3+2 = 7 marks)

Classification of NSAIDs

• Celecoxib, Etoricoxib, Parecoxib

• Nimesulide, Diclofenac

Uses of Aspirin

1. Analgesic: Mild to moderate pain - headache, arthralgia, myalgia, dental pain, dysmenorrhea. At doses of 2 x 325 mg (650 mg) QID.
2. Antipyretic: Lowers fever by inhibiting PGE2 synthesis in the hypothalamus, resetting the thermostat to normal.
3. Anti-inflammatory: Requires higher doses (12-20 tablets/day, i.e., ~3-6 g/day) for anti-inflammatory effect in rheumatic fever, rheumatoid arthritis, osteoarthritis.
4. Antiplatelet / Cardioprotection: Low-dose aspirin (75-150 mg/day) irreversibly inhibits COX-1 in platelets, reducing TXA2 formation and platelet aggregation. Used in:
   • Prevention of MI and stroke (secondary prevention)
   • Acute coronary syndromes
   • Post-CABG, post-angioplasty
5. Kawasaki disease: High-dose aspirin is part of standard therapy.
6. Dental use: Analgesic for toothache and post-extraction pain (though caution needed due to bleeding risk in dental procedures).

Adverse Effects of Aspirin

• Dyspepsia, nausea, epigastric discomfort
• Gastric erosions and ulceration (inhibits COX-1, reducing protective PGI2 and PGE2 in gastric mucosa)
• GI bleeding - may be occult or frank hematemesis
• Take with food/milk to reduce GI irritation

• Irreversibly acetylates COX-1 in platelets for their entire lifetime (7-10 days)
• Prolongs bleeding time
• Must be withheld at least 1 week before elective surgery or dental procedures
• Important consideration before tooth extractions

• Inhibits renal prostaglandins (PGE2, PGI2) that maintain renal blood flow
• Causes sodium and water retention, edema
• Can precipitate acute kidney injury in susceptible patients

• Low-dose aspirin is cardioprotective (reduces TXA2)
• High-dose aspirin reduces PGI2 (vasoprotective), potentially harmful

• In aspirin-sensitive individuals, COX inhibition shifts arachidonic acid toward leukotriene synthesis, triggering bronchospasm
• Aspirin triad: Asthma + Nasal polyps + Aspirin sensitivity

• Tinnitus (ringing in ears), headache, dizziness, reversible hearing loss

• Early: Respiratory alkalosis (stimulation of respiratory center)
• Late: Metabolic acidosis, hyperthermia, dehydration, coma
• Treatment: Alkalinization of urine (sodium bicarbonate), forced diuresis, dialysis

• A rare but serious condition (hepatic encephalopathy) when aspirin is given to children with viral infections (influenza, chickenpox)
• Aspirin is contraindicated in children under 16 years

• Increases risk of post-extraction bleeding; must be stopped pre-operatively
• Can cause oral ulcers if placed directly on gingival tissue

Q.2 Classify antihypertensive drugs. Write the mechanism of action and adverse effects of ACE Inhibitors. (2+2+3 = 7 marks)

Classification of Antihypertensive Drugs

• Thiazides: Hydrochlorothiazide, Chlorthalidone
• Loop diuretics: Furosemide
• Potassium-sparing: Spironolactone, Amiloride

• Non-selective: Propranolol, Nadolol
• Cardioselective (β1): Atenolol, Metoprolol, Bisoprolol
• With ISA: Pindolol, Acebutolol
• Combined α+β blockers: Labetalol, Carvedilol

• Captopril, Enalapril, Lisinopril, Ramipril, Perindopril

• Losartan, Valsartan, Telmisartan, Olmesartan

• Dihydropyridines: Amlodipine, Nifedipine, Felodipine
• Non-dihydropyridines: Verapamil (phenylalkylamine), Diltiazem (benzothiazepine)

• Prazosin, Terazosin, Doxazosin

• Clonidine (α2 agonist), Methyldopa

• Hydralazine, Minoxidil, Sodium nitroprusside

• Renin inhibitors: Aliskiren
• Aldosterone receptor antagonists: Eplerenone

Mechanism of Action of ACE Inhibitors

1. Inhibit ACE enzyme: ACE normally converts Angiotensin I (inactive) → Angiotensin II (potent vasoconstrictor).
2. Reduce Angiotensin II: This leads to:
   • Vasodilation (reduced peripheral vascular resistance)
   • Reduced aldosterone secretion → less sodium and water retention → decreased blood volume
   • Decreased sympathetic activation
3. Prevent bradykinin breakdown: ACE normally degrades bradykinin (vasodilator). ACE inhibitors allow bradykinin to accumulate, contributing further to vasodilation.
4. Net effect: Reduction in both preload and afterload, lowering systolic and diastolic blood pressure.

Adverse Effects of ACE Inhibitors

PART B (Short Notes)

Q.3 Write short notes on the following: (4 x 4 = 16 marks)

(i) Mummifying Agents

• Formocresol (Buckley's formocresol): A mixture of formaldehyde (19%), cresol (35%), glycerine, and water. Most widely used. Formaldehyde acts as a fixative/mummifying agent; cresol has antiseptic properties.
• Glutaraldehyde: Less toxic alternative to formocresol; causes less periapical inflammation.
• Paraformaldehyde paste (Triopaste): Slow-release formaldehyde for devitalization of pulp over a few days.

• Vital pulpotomy in deciduous teeth
• Infected pulp treatment where complete root canal therapy is not feasible
• Emergency treatment when multi-visit RCT is not possible

• Periapical irritation and inflammation if material extrudes beyond apex
• Toxicity to periapical tissues (formaldehyde is cytotoxic)
• Mutagenic/carcinogenic potential of formaldehyde (hence, glutaraldehyde preferred in modern practice)
• Can cause discoloration of tooth

(ii) Selective COX-2 Inhibitors

• Gastric mucosal protection (PGE2, PGI2)
• Platelet TXA2 synthesis
• Renal blood flow maintenance

• Celecoxib - still in clinical use; contains a sulfonamide group
• Rofecoxib (withdrawn - increased MI risk), Valdecoxib (withdrawn), Etoricoxib, Parecoxib (IV prodrug of valdecoxib)

• Osteoarthritis and rheumatoid arthritis
• Acute pain and dysmenorrhea
• Familial adenomatous polyposis (celecoxib)
• Post-operative pain (parecoxib)
• Patients at high GI risk who need NSAID therapy

• Cardiovascular risk (major limitation): Inhibition of COX-2-derived PGI2 (which is vasodilatory and anti-aggregatory at endothelium) without reducing TXA2 tips the balance toward vasoconstriction and thrombosis → increased risk of MI and stroke. This led to withdrawal of rofecoxib (VIGOR trial).
• Headache, dyspepsia, abdominal pain, diarrhea
• Hypertension, edema (retain renal effects similar to non-selective NSAIDs)
• Renal impairment (same as non-selective NSAIDs)
• No antiplatelet effect - GI advantage is lost when low-dose aspirin is added co-currently
• Sulfonamide allergy (celecoxib - contraindicated in sulfa allergy)

(iii) Lignocaine-Adrenaline Combination

1. Prolonged duration of action: Adrenaline (a vasoconstrictor) constricts local blood vessels (via α1 adrenergic receptors), reducing blood flow at the injection site. This slows absorption of lignocaine into the systemic circulation, keeping it concentrated at the nerve for longer.
2. Reduced systemic toxicity: By slowing absorption, peak plasma levels of lignocaine are reduced, decreasing the risk of CNS and cardiovascular toxicity.
3. Improved depth and quality of anaesthesia: Better local concentration leads to more reliable nerve block.
4. Haemostasis: Vasoconstriction reduces bleeding in the operative field, providing a clearer surgical site during dental procedures.
5. Reduced dose requirement: Less lignocaine is needed to achieve adequate anaesthesia.

• Uncontrolled hypertension or severe cardiovascular disease
• Uncontrolled hyperthyroidism
• Use with caution in patients on tricyclic antidepressants or non-selective beta-blockers (risk of hypertensive crisis)
• Use minimal effective dose in cardiac patients

(iv) Local Styptics

• Alum (aluminium potassium sulfate)
• Ferric sulfate / Ferric chloride (Monsel's solution)
• Silver nitrate
• Tannic acid
• Zinc chloride

• Surgicel - acts as a mechanical matrix for clot formation; biodegradable

• Bovine or recombinant thrombin applied locally converts fibrinogen → fibrin directly; used in surgical bleeding

• Gelfoam - absorbable gelatin sponge; placed in extraction socket; provides scaffold for clot organization

• Waxy mixture used to pack bleeding bone surfaces (e.g., in craniofacial surgery); not absorbable

• Adrenaline applied topically on retraction cord causes local vasoconstriction and hemostasis

• Post-extraction bleeding control
• Gingival retraction before impressions (astringent-impregnated retraction cords)
• Control of bleeding during cavity preparation
• Periapical surgery and flap procedures
• Pulp capping procedures

Q.4 Fill in the blanks: (5 x 1 = 5 marks)

• Protamine sulfate is the specific antidote for heparin toxicity/overdose.
• It is a positively charged protein that binds to heparin (negatively charged) to form an inactive stable complex, neutralizing its anticoagulant effect.
• Dose: 1 mg protamine for every 100 units of heparin administered.

• More specifically, this is an example of pharmacokinetic synergism (or adjuvant use) - the adrenaline does not enhance the mechanism of the LA per se, but by causing vasoconstriction, it reduces absorption and prolongs the local tissue concentration of lignocaine.
• Some textbooks describe this as an example of local vasoconstriction enhancing LA effect - the combination exemplifies use of an adjuvant/additive combination for prolonging the duration and improving efficacy of local anaesthesia.

Sources: Lippincott Illustrated Reviews: Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology