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I now have enough foundational data from the library. Let me compile comprehensive answers to all questions on this BDS exam paper.

BDS 2nd Professional - General & Dental Pharmacology & Therapeutics (2022-23)

PART A

Q.1 Classify Antianginal Drugs. Discuss Therapeutic Uses and Adverse Effects of Nitrates. (2+2+3 = 7)

Classification of Antianginal Drugs

I. Organic Nitrates

Short-acting: Glyceryl trinitrate (GTN / Nitroglycerin) - sublingual
Long-acting: Isosorbide dinitrate (ISDN), Isosorbide-5-mononitrate (ISMN)

II. Beta-Adrenergic Blockers

Propranolol, Metoprolol, Atenolol

III. Calcium Channel Blockers

Dihydropyridines: Amlodipine, Nifedipine
Non-dihydropyridines: Verapamil, Diltiazem

IV. Potassium Channel Openers

Nicorandil

V. Others

Ranolazine (late Na+ current inhibitor)
Ivabradine (If channel blocker)
Trimetazidine

Mechanism of Action of Nitrates

Organic nitrates are biotransformed intracellularly to release nitric oxide (NO), which activates guanylyl cyclase, raising cGMP levels in vascular smooth muscle - leading to vasodilation.

Haemodynamic effects:

Preload reduction (main effect): Dilation of venous capacitance vessels reduces venous return, reduces ventricular end-diastolic volume, and decreases myocardial O2 consumption (law of Laplace).
Afterload reduction (at higher doses): Arteriolar dilation reduces peripheral resistance.
Redistribution of coronary blood flow toward ischemic subendocardium.
In vasospastic angina: direct coronary vasodilation relieves spasm.

(Goodman & Gilman's, Block 9 - Mechanisms of Antianginal Efficacy of Organic Nitrates)

Therapeutic Uses of Nitrates

Stable (effort) angina - Sublingual GTN for acute attacks; long-acting nitrates for prophylaxis.
Unstable angina - IV nitroglycerin.
Vasospastic (Prinzmetal's) angina - Nitrates relieve coronary spasm.
Acute myocardial infarction - Reduces preload and infarct size.
Acute heart failure / Pulmonary edema - Reduces preload dramatically.
Hypertensive emergencies - IV sodium nitroprusside.
Pulmonary hypertension in neonates - Inhaled NO (approved).

Adverse Effects of Nitrates

Adverse Effect	Mechanism
Headache (most common)	Dilation of meningeal/cerebral vessels
Flushing	Cutaneous vasodilation
Postural (orthostatic) hypotension	Excessive preload reduction
Reflex tachycardia	Compensatory sympathetic activation
Syncope	Profound hypotension
Methemoglobinemia	At very high doses (rare)
Tolerance	Most important; develops within 24-48 hrs of continuous use

Nitrate tolerance is avoided by a nitrate-free interval of 8-12 hours (e.g., removing transdermal patch at night).

Contraindication: Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) - risk of severe, potentially fatal hypotension.

Q.2 Classify Local Anaesthetic Drugs. Write the Mechanism of Action, Uses and Adverse Effects of Lignocaine. (2+3+2 = 7)

Classification of Local Anaesthetics

A. Based on Chemical Structure:

Esters	Amides
Cocaine	Lignocaine (Lidocaine)
Procaine	Bupivacaine
Benzocaine	Ropivacaine
Tetracaine (Amethocaine)	Mepivacaine
Chloroprocaine	Prilocaine

Esters are metabolised by plasma cholinesterase; amides by hepatic microsomal enzymes.

B. Based on Duration of Action:

Short-acting: Procaine, Chloroprocaine
Intermediate-acting: Lignocaine, Mepivacaine
Long-acting: Bupivacaine, Ropivacaine, Tetracaine

Mechanism of Action of Lignocaine

Lignocaine blocks voltage-gated sodium (Na+) channels in the axonal membrane.

It gains access to the channel from the intracellular side (enters as uncharged base, ionizes inside).
Binds to Na+ channels in the inactivated state, preventing them from returning to the resting (open-capable) state.
This prevents the depolarization phase of the action potential.
Conduction block is use-dependent (more effective in rapidly firing fibers - local anesthesia is therefore more effective in pain fibers which have higher firing rates).
Order of fiber blockade: Small myelinated > small unmyelinated > large myelinated fibers.
Pain and temperature (C and Aδ) blocked first, then proprioception, then touch/pressure, then motor last.

Uses of Lignocaine

A. In Dentistry:

Infiltration anesthesia (for minor extractions, restorations)
Nerve block anesthesia (inferior alveolar nerve block, mental nerve block)
Topical anesthesia (mucous membranes before injections - as gel/spray)
Intraligamentary (periodontal ligament) injection

B. General Medical Uses:

Surface/topical anaesthesia (throat, larynx, urethra)
Spinal (intrathecal) anesthesia
Epidural anesthesia
IV regional anesthesia (Bier's block)
Anti-arrhythmic: Class IB anti-arrhythmic - used for ventricular arrhythmias especially post-MI

Adverse Effects of Lignocaine

CNS (dose-dependent, progressive):

Sedation, dizziness, tinnitus, blurred vision
Circumoral numbness
Disorientation, slurred speech
Convulsions (higher doses)
Respiratory depression, coma (toxic doses)

Cardiovascular:

Hypotension (vasodilation)
Bradycardia
Cardiac arrest (very high doses)

Local tissue toxicity:

Transient neurological symptoms at high concentrations

Allergic reactions:

Rare with amides; more common with ester-type LA
Methylparaben preservative in lignocaine vials can cause allergy

Important for dentistry - role of adrenaline (epinephrine):

Added at 1:80,000 or 1:200,000 concentration
Causes local vasoconstriction - prolongs duration of action, reduces systemic absorption and toxicity, reduces bleeding in the field
Contraindicated in patients on non-selective beta-blockers (risk of hypertensive crisis)

Q.3 Short Notes (4 × 4 = 16)

(i) Factors Modifying Action of a Drug

Drug action is not uniform - it is influenced by many patient and drug-related factors:

1. Age:

Neonates/infants: Immature liver/kidney enzymes - reduced drug metabolism/excretion; increased sensitivity (e.g., morphine, chloramphenicol - gray baby syndrome)
Elderly: Reduced hepatic and renal function, decreased plasma albumin, altered body composition - increased drug sensitivity

2. Body Weight and Body Surface Area:

Dose is often calculated per kg body weight
Obese patients: altered volume of distribution for lipophilic drugs

3. Sex:

Women have higher body fat (altered Vd for lipophilic drugs), lower plasma volume
Pharmacokinetic differences in CYP450 expression

4. Genetics (Pharmacogenetics):

Slow vs. fast acetylators (isoniazid, procainamide)
G6PD deficiency (hemolysis with oxidant drugs)
Pseudocholinesterase deficiency (prolonged succinylcholine action)
CYP2D6 polymorphism (codeine toxicity)

5. Pathological states:

Hepatic disease: Reduced metabolism of drugs (e.g., lidocaine, warfarin)
Renal disease: Reduced excretion (e.g., aminoglycosides, digoxin - dose adjustment needed)
Hypoalbuminemia: More free drug available

6. Drug Interactions:

Pharmacokinetic (affecting absorption, distribution, metabolism, excretion)
Pharmacodynamic (additive, synergistic, antagonistic effects)

7. Route of Administration:

IV = immediate effect, 100% bioavailability; Oral = subject to first-pass metabolism
Sublingual bypasses first-pass metabolism (e.g., GTN)

8. Tolerance:

Reduced response with repeated drug administration (e.g., nitrate tolerance, opioid tolerance)

9. Psychological factors:

Placebo effect - expectation can modify drug response

10. Diet and Environment:

Grapefruit juice inhibits CYP3A4 (increases levels of statins, calcium blockers)
Smoking induces CYP1A2 (reduces efficacy of theophylline, olanzapine)

(ii) Treatment of Organophosphorus Poisoning

Organophosphorus (OP) compounds (pesticides like parathion, malathion; nerve agents) irreversibly inhibit acetylcholinesterase (AChE), causing accumulation of acetylcholine at all cholinergic synapses.

Clinical features (SLUDGE/DUMBELS):

Muscarinic: Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis; Bradycardia, bronchospasm, miosis
Nicotinic: Muscle fasciculations, weakness, paralysis (including respiratory muscles)
CNS: Anxiety, convulsions, coma

Treatment:

1. General measures:

Remove patient from exposure
Remove contaminated clothing, wash skin thoroughly
Maintain airway, breathing, circulation
Gastric lavage if ingested (within 1 hour)

2. Specific Antidotes:

Drug	Dose	Mechanism
Atropine (drug of choice for muscarinic symptoms)	2-4 mg IV, repeat every 5-10 min until secretions dry	Competitive antagonist at muscarinic receptors - blocks bronchospasm, bradycardia, hypersecretion
Pralidoxime (2-PAM)	1-2 g IV over 15-30 min, then infusion	Reactivates inhibited AChE by removing OP from the enzyme active site - effective if given before "aging" (irreversible binding, 24-48 hours) - acts on nicotinic symptoms (muscle paralysis)
Diazepam	5-10 mg IV	Controls convulsions

3. Intermediate syndrome (24-96 hrs after acute phase): Proximal limb weakness, cranial nerve palsy, respiratory failure - does NOT respond to atropine; requires ventilatory support.

(Adams and Victor's Neurology; Goldman-Cecil Medicine)

(iii) Treatment of Bronchial Asthma

Asthma is characterized by reversible airflow obstruction, airway hyperresponsiveness, and chronic eosinophilic inflammation.

Classification for treatment:

Mild intermittent
Mild persistent
Moderate persistent
Severe persistent

Drugs used:

A. Bronchodilators (Relievers):

Beta-2 agonists:

Short-acting (SABA): Salbutamol (albuterol), Terbutaline - first-line for acute attacks; inhaled
Long-acting (LABA): Salmeterol, Formoterol - used with inhaled corticosteroids; NOT as monotherapy

Anticholinergics:

Short-acting: Ipratropium bromide - useful in COPD; also in acute severe asthma
Long-acting: Tiotropium (add-on in severe asthma)

Methylxanthines:

Theophylline, Aminophylline - phosphodiesterase inhibitors; narrow therapeutic index
Used as add-on; IV aminophylline in acute severe asthma

B. Anti-inflammatory (Controllers):

Inhaled corticosteroids (ICS) - cornerstone of persistent asthma management

Beclomethasone, Budesonide, Fluticasone
Reduce airway inflammation, hyperresponsiveness
Local side effects: oral candidiasis, dysphonia

Systemic corticosteroids - Prednisolone for acute exacerbations
Leukotriene receptor antagonists - Montelukast, Zafirlukast

Useful in aspirin-sensitive asthma, exercise-induced asthma

Mast cell stabilisers - Sodium cromoglycate, Nedocromil - prophylactic, not for acute attacks
Biologics (severe asthma):

Omalizumab (anti-IgE)
Mepolizumab, Benralizumab (anti-IL-5 for eosinophilic asthma)
Dupilumab (anti-IL-4/13)

Stepwise therapy (GINA guidelines):

Step 1: SABA PRN
Step 2: Low-dose ICS + SABA PRN
Step 3: Low-dose ICS + LABA
Step 4: Medium-dose ICS + LABA
Step 5: Add-on biologics or oral steroids

(iv) Styptics

Styptics (also called haemostatics or astringents) are agents that arrest or stop bleeding, particularly in dentistry and minor surgical procedures.

Classification:

A. Local Haemostatic Agents:

Mechanical styptics:

Absorbable gelatin sponge (Gelfoam) - provides scaffold for clot formation
Oxidised cellulose (Surgicel) - forms clot when in contact with blood
Bone wax - mechanical occlusion of bone vessels
Collagen sponge / fibres

Chemical/vasoconstrictor styptics:

Adrenaline (epinephrine) - local vasoconstriction; used in LA solutions and as topical application (ferric sulfate compound)
Ferric sulfate (Astringedent, ViscoStat) - precipitates blood proteins, causes vasoconstriction; used in gingival retraction
Aluminium chloride - gingival retraction and haemostasis in dental procedures
Tannic acid - precipitates proteins

Coagulation-promoting agents:

Thrombin (topical) - directly converts fibrinogen to fibrin
Fibrin sealants - combination of thrombin + fibrinogen
Vitamin K - for bleeding due to warfarin/vitamin K deficiency (parenteral/oral)
Tranexamic acid - antifibrinolytic; inhibits plasminogen activation; used as oral rinse post-extraction in patients on anticoagulants

Systemic agents:

Vitamin K (phytonadione) - for coumarin-related bleeding
Tranexamic acid (oral/IV)
Desmopressin (DDAVP) - for mild hemophilia A and von Willebrand disease
Fresh frozen plasma (FFP), cryoprecipitate - for coagulation factor deficiencies

Dental relevance:

Aluminium chloride and ferric sulfate are widely used in gingival retraction prior to impressions and for socket haemostasis.
Tranexamic acid mouthwash (4.8%) is used post-extraction in anticoagulated patients to reduce the need for reversing anticoagulation.

Q.4 Fill in the Blanks (5 × 1 = 5)

#	Answer
(i) ________ route bypasses the first pass metabolism.	Sublingual (also parenteral/IV/transdermal)
(ii) ________ is a chelating agent.	Desferrioxamine (also EDTA, Penicillamine, Dimercaprol/BAL, DMSA)
(iii) ________ is an adverse effect of long-term aspirin therapy.	Peptic ulcer / Gastric ulcer (also: GI bleeding, tinnitus/salicylism)
(iv) ________ is an example of an antihistaminic drug.	Chlorpheniramine (also: diphenhydramine, cetirizine, loratadine)
(v) ________ is a selective COX-2 inhibitor.	Celecoxib (also: etoricoxib, rofecoxib)

Partial PART B Questions (visible at bottom of image)

(i) Plasma half-life and its importance - Key pharmacokinetic parameter; time for plasma concentration to halve; determines dosing interval; relevant to accumulation and washout.

(ii) Combination of a local anaesthetic with adrenaline - Adrenaline (1:80,000 - 1:200,000) added to LA prolongs duration, reduces peak plasma concentration (reduces systemic toxicity), decreases surgical bleeding. Contraindicated in patients on non-selective beta-blockers, in end-arteries (digits, nose, penis, ear), and should be used with caution in severe hypertension and cardiac arrhythmias.

Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics (Antianginal mechanisms); Adams and Victor's Principles of Neurology (Organophosphate poisoning); Goldman-Cecil Medicine (Antidotes); standard BDS pharmacology curriculum (KD Tripathi / Rang & Dale framework).

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