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Answer these questions for board exam of bds 1st year pharmacology kathamndu university answers format

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All answers are written above. Here is a quick summary of what's covered:

Summary of All Answers Covered

LAQs (Long Answer Questions)

#QuestionMarks
1Define bioavailability + factors affecting drug absorption[1+4=5]
2Short notes: TDM, first-pass, nomenclature, ADR, antagonist, superinfection, agonist/antagonist, drug dependence, plasma half-life, GPCRMultiple
3Routes of drug administration + sublingual advantages/disadvantages[4+2=6]
4Drug absorption + factors[1+4=5]
5Biotransformation + Phase I reactions[1+4=5]
6Oral, parenteral, IV route advantages/disadvantages[8]
7Bioavailability + bioequivalence + therapeutic half-life significance[2+1]
8Pharmacokinetics/pharmacodynamics + 4 major factors affecting drug response[1+1+4=6]
9Types of drug antagonism with examples[1+1+4=6]

SAQs (Short Answer Questions)

  • Enterohepatic circulation
  • Agonist and antagonist
  • Fluconazole (mechanism, uses, interactions)
  • Propranolol (mechanism, uses, contraindications)
  • Pralidoxime (mechanism, use in organophosphate poisoning)
  • Advantages of atenolol over propranolol
  • Types of antagonism
All answers are formatted for board-exam standards (Kathmandu University BDS 1st Year) with definitions, mechanisms, classifications, tables, and examples as required by the mark allocations.
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Answer these questions for bds 1st year pharmacology exam of kathamndu university each question holds 5 marks

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RESPIRATORY SYSTEM - PHARMACOLOGY

BDS 1st Year | Kathmandu University | Board Exam Answers (5 Marks Each)

SHORT NOTES (5 Marks Each)

1. Use of Salbutamol in Bronchial Asthma

Salbutamol (Albuterol) is a selective short-acting beta-2 adrenergic agonist (SABA) and the most widely used bronchodilator in asthma.
Mechanism of Action: Salbutamol selectively activates beta-2 adrenergic receptors on bronchial smooth muscle. This activates adenylyl cyclase via Gs protein, increasing intracellular cAMP, which activates Protein Kinase A (PKA). PKA phosphorylates myosin light chain kinase (MLCK), reducing its activity, causing smooth muscle relaxation and bronchodilation. Onset: 5 minutes; Duration: 4-6 hours.
Uses in Bronchial Asthma:
  1. Acute bronchospasm (first-line rescue therapy): Inhaled salbutamol via MDI (metered dose inhaler) or nebulization is the drug of choice for acute asthma attacks
  2. Exercise-induced asthma: Used as prophylaxis 15-20 min before exercise
  3. Acute severe asthma (status asthmaticus): Continuous nebulization or IV infusion used
Route: Inhalation (preferred - direct delivery, fewer systemic effects), oral, IV
Adverse Effects:
  • Tremor (most common - hands), palpitations, tachycardia (beta-1 spillover at high doses)
  • Hypokalemia (K+ shift into cells)
  • Headache, nervousness, hyperglycemia
Note: Salbutamol is a reliever drug - for acute attacks. It does not treat underlying inflammation.

2. Combination Therapy in Tuberculosis

Rationale for Combination Therapy: M. tuberculosis has a slow doubling time (18-24 hours). Natural mutations occur spontaneously in large bacterial populations, producing organisms resistant to individual drugs. Combination therapy:
  1. Prevents drug resistance - each drug kills organisms resistant to the other
  2. Increases bactericidal activity - synergistic killing of different subpopulations
  3. Shortens treatment duration
  4. Prevents relapse
Standard Regimen (DOTS - Directly Observed Treatment Short-course):
Intensive Phase (2 months): Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E)
  • Written as: 2HRZE
Continuation Phase (4 months): Isoniazid (H) + Rifampicin (R)
  • Written as: 4HR
Total duration: 6 months
Each drug targets a different bacterial population:
  • Isoniazid: Kills rapidly dividing extracellular bacilli
  • Rifampicin: Kills "persisters" (slowly metabolizing intracellular bacilli) - most important sterilizing drug
  • Pyrazinamide: Active in acidic environment of macrophages
  • Ethambutol: Bacteriostatic, prevents emergence of resistance

3. First-Line Antitubercular Drugs

The four first-line drugs are: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (mnemonic: RIPE)
DrugMechanismKey Adverse Effects
Isoniazid (INH)Inhibits mycolic acid synthesis (KatG activation → InhA inhibition)Hepatotoxicity, peripheral neuropathy (↓B6), SLE-like syndrome
RifampicinInhibits bacterial RNA polymerase (beta subunit)Red/orange discoloration of secretions, hepatotoxicity, CYP450 inducer
PyrazinamideConverted to pyrazinoic acid in macrophages; disrupts membrane potentialHyperuricemia/gout, hepatotoxicity
EthambutolInhibits arabinogalactan synthesis (cell wall)Optic neuritis (red-green color blindness, visual disturbance)
Streptomycin is sometimes listed as a 5th first-line agent (inhibits 30S ribosome).

4. Bronchodilators

Bronchodilators relax bronchial smooth muscle, widen the airways, and reduce airflow resistance.
Classification:
1. Beta-2 Adrenergic Agonists
  • Short-acting (SABA): Salbutamol, Terbutaline (rescue inhalers, onset 5 min)
  • Long-acting (LABA): Salmeterol, Formoterol (maintenance, duration 12h+)
  • MOA: Activate beta-2 receptors → ↑cAMP → smooth muscle relaxation
2. Methylxanthines
  • Theophylline, Aminophylline
  • MOA: Non-selective PDE inhibition → ↑cAMP; adenosine receptor antagonism; anti-inflammatory
  • Narrow therapeutic index; requires TDM
3. Anticholinergics (Muscarinic antagonists)
  • Short-acting: Ipratropium bromide (SAMA)
  • Long-acting: Tiotropium (LAMA)
  • MOA: Block M3 muscarinic receptors on bronchial smooth muscle → prevent bronchoconstriction
  • More useful in COPD than asthma

5. Mucolytics

Mucolytics are drugs that reduce the viscosity of mucus in the airways, facilitating its clearance.
Mechanism:
  • Acetylcysteine (N-acetylcysteine/NAC): Contains free -SH (thiol) group that breaks disulfide bonds in mucus glycoproteins, reducing viscosity. Also used as antidote in paracetamol overdose.
  • Bromhexine: Depolymerizes mucopolysaccharide fibers; stimulates serous glands. Active metabolite: ambroxol (more potent).
  • Ambroxol: Reduces mucus viscosity; stimulates surfactant production; anti-inflammatory properties.
  • Carbocisteine: Acts on goblet cells to normalize sialomucin:fucomucin ratio.
  • Dornase alfa (DNase): Breaks down DNA in purulent sputum (used in cystic fibrosis).
Uses: Chronic bronchitis, COPD, cystic fibrosis, bronchiectasis

6. Drugs Used in Productive Cough

Productive (wet) cough serves to clear secretions - suppression is generally not indicated.
Management focuses on:
1. Expectorants - Increase volume and reduce viscosity of secretions
  • Guaifenesin: Most widely used; stimulates bronchial secretions by reflex action
  • Potassium iodide: Stimulates bronchial gland secretion
  • Steam inhalation: Humidifies secretions
2. Mucolytics - Break down mucus (see above: acetylcysteine, bromhexine, ambroxol)
3. Treat the underlying cause:
  • Antibiotics if bacterial infection (pneumonia, bronchitis)
  • Bronchodilators if bronchoconstriction present
Note: Antitussives (codeine, dextromethorphan) are CONTRAINDICATED in productive cough as they suppress the clearing of secretions.

7. Expectorants

Definition: Drugs that facilitate removal of respiratory secretions by increasing the volume of respiratory tract fluid (making sputum less viscous and easier to expectorate).
Classification and Mechanisms:
1. Reflex Expectorants (Nauseants):
  • Act on gastric mucosa → stimulate vagal afferents → reflex increase in bronchial secretions
  • Examples: Guaifenesin (most popular OTC), Ipecac syrup, Potassium iodide, Ammonium chloride
  • Guaifenesin: 200-400 mg every 4 hours with plenty of water
2. Direct Stimulant Expectorants:
  • Directly stimulate bronchial glands
  • Examples: Potassium iodide (high doses), Creosote, Terpin hydrate
3. Volatiles / Steam Inhalations:
  • Menthol, Eucalyptus oil, Turpentine oil - soothing effect; mild expectorant
Uses: Upper respiratory tract infections, chronic bronchitis, bronchiectasis
Adverse Effects: Nausea and vomiting (especially with high doses), iodism (with iodides - rash, salivary gland swelling)

8. Sodium Cromoglycate (Cromolyn Sodium)

Class: Mast cell stabilizer / Anti-allergic / Anti-inflammatory (prophylactic)
Mechanism of Action: Sodium cromoglycate stabilizes mast cell membranes by blocking calcium channels, preventing mast cell degranulation and release of inflammatory mediators (histamine, leukotrienes, prostaglandins, and serotonin) in response to allergen or exercise.
  • Also inhibits early and late phase allergic responses
  • May inhibit eosinophil and neutrophil activation
  • Does NOT have bronchodilator activity
Pharmacokinetics:
  • Administered by inhalation (MDI, dry powder, nebulization)
  • Very poor oral absorption (<1%)
  • No hepatic metabolism - excreted unchanged in bile and urine
  • Onset: Not immediate - requires regular use for 2-4 weeks before full benefit
Uses:
  1. Prophylaxis of bronchial asthma (mild to moderate persistent asthma - especially in children and exercise-induced)
  2. Allergic rhinitis (nasal spray)
  3. Allergic conjunctivitis (eye drops)
  4. Food allergy (oral capsules, given pre-meal)
Adverse Effects (minimal - very safe):
  • Local: throat irritation, cough, bronchospasm (paradoxical - rare)
  • Headache
  • Safe in pregnancy and children
Important: NOT used for acute attacks - only prophylaxis; no role once attack has started.

LONG ANSWER QUESTIONS (LAQs)

LAQ 1. List the first-line antitubercular drugs. Write the mechanism of action, uses, and adverse effects of Isoniazid. Explain the rationale of combination therapy for treatment of tuberculosis. [1+2+1+1+1=6]

First-Line Anti-TB Drugs

  1. Isoniazid (H)
  2. Rifampicin (R)
  3. Pyrazinamide (Z)
  4. Ethambutol (E) (5. Streptomycin - sometimes included)

Isoniazid (INH)

Mechanism of Action:
  • Isoniazid is a prodrug activated by the mycobacterial enzyme KatG (catalase-peroxidase)
  • The activated form binds to and inhibits InhA (enoyl-ACP reductase) and KasA (beta-ketoacyl-ACP synthase)
  • These enzymes are essential for mycolic acid synthesis - the main lipid component of the mycobacterial cell wall
  • Disruption of mycolic acid synthesis leads to loss of cell wall integrity and bacterial death
  • Free radicals (including nitric oxide) also generated contribute to bactericidal action
  • Bactericidal for rapidly dividing bacilli; bacteriostatic for resting organisms
Uses:
  1. First-line treatment of active TB (always in combination: 2HRZE → 4HR)
  2. Treatment of latent TB infection (LTBI) - 6-9 months isoniazid monotherapy
  3. Prophylaxis in high-risk contacts (HIV patients, close contacts of active TB)
Adverse Effects:
  1. Peripheral neuropathy (most common) - due to competitive inhibition of pyridoxine (Vitamin B6); prevented by supplementing pyridoxine 25-50 mg/day
  2. Hepatotoxicity (most serious) - elevated liver enzymes, drug-induced hepatitis; more common in slow acetylators and alcoholics; monitor LFTs
  3. SLE-like syndrome - antinuclear antibodies; more in slow acetylators
  4. CNS effects: Dizziness, euphoria, psychosis, convulsions (especially in overdose)
  5. Drug interactions: Inhibits CYP2C9/CYP2D6; increases phenytoin and carbamazepine levels
Pharmacogenetics: Fast acetylators (more common in Asian populations) have shorter t1/2 (~1.5h) but may have less hepatotoxicity; slow acetylators accumulate drug → more neuropathy

Rationale of Combination Therapy

M. tuberculosis populations naturally contain rare spontaneous mutants resistant to individual drugs (frequency ~1 in 10^6). In a large bacterial load (active TB lesion can contain 10^8 organisms), mutants resistant to any single drug are virtually guaranteed to pre-exist. Giving a single drug will selectively kill the susceptible organisms while the resistant mutants proliferate.
When two or more drugs are given:
  • The probability that a single organism is resistant to two drugs simultaneously is ~10^-6 × 10^-6 = 10^-12 (practically impossible)
  • Each drug kills organisms resistant to the other, preventing emergence of resistance
  • Different drugs target different subpopulations:
    • Rapidly growing extracellular: killed by INH
    • Semi-dormant intracellular (acidic macrophage): killed by Pyrazinamide
    • "Persisters" (slowly metabolizing): killed by Rifampicin

LAQ 2. Classify drugs used in therapy of bronchial asthma with at least one example. Write the mechanism of action of Theophylline. Mention its two indications, two adverse effects, and two drug interactions. [3+1+1+1+1+1+1=9] / MOA, adverse effects of aminophylline. [1+1=2]

Classification of Drugs Used in Bronchial Asthma

A. Bronchodilators (Relievers)
  1. Beta-2 Adrenergic Agonists
    • SABA: Salbutamol (albuterol), Terbutaline
    • LABA: Salmeterol, Formoterol (used with ICS)
  2. Methylxanthines
    • Theophylline (oral), Aminophylline (IV)
  3. Anticholinergics
    • Ipratropium bromide (SAMA), Tiotropium (LAMA)
B. Anti-inflammatory Drugs (Controllers)
  1. Inhaled Corticosteroids (ICS) - mainstay of persistent asthma
    • Beclomethasone, Budesonide, Fluticasone
  2. Leukotriene Receptor Antagonists (LTRAs)
    • Montelukast, Zafirlukast
  3. Mast Cell Stabilizers
    • Sodium cromoglycate, Nedocromil sodium
  4. Anti-IgE Antibody
    • Omalizumab (biological agent, severe allergic asthma)
  5. Systemic Corticosteroids (acute severe asthma)
    • Prednisolone (oral), Hydrocortisone (IV)

Mechanism of Action of Theophylline

Theophylline is a methylxanthine (structurally related to caffeine). It has multiple mechanisms:
  1. Non-selective PDE (Phosphodiesterase) inhibition:
    • Inhibits phosphodiesterase (PDE3, PDE4) enzymes that normally break down cAMP and cGMP
    • Inhibition → ↑intracellular cAMP → activates PKA → smooth muscle relaxation → bronchodilation
    • Also reduces inflammatory cell activity (eosinophils, mast cells, T-lymphocytes)
  2. Adenosine receptor antagonism:
    • Adenosine causes bronchoconstriction in asthmatic airways (by releasing histamine/leukotrienes)
    • Theophylline blocks adenosine A1/A2 receptors, preventing bronchoconstriction
    • Adenosine antagonism also responsible for toxic effects (cardiac arrhythmias, seizures)
  3. Anti-inflammatory effects:
    • Stimulates IL-10 release (anti-inflammatory cytokine)
    • Inhibits NF-kB transcription factor, reducing inflammatory gene expression
    • At low doses, activates histone deacetylase (HDAC2), enhancing corticosteroid effects
  4. Stimulation of diaphragm contractility - improves respiratory muscle function
Indications:
  1. Asthma (add-on therapy for persistent asthma not controlled on ICS + LABA)
  2. COPD (add-on oral bronchodilator)
  3. Acute severe asthma (IV aminophylline)
  4. Apnea of prematurity (caffeine preferred now)
Adverse Effects of Theophylline/Aminophylline:
(Narrow therapeutic index: therapeutic range = 10-20 mcg/mL; toxic effects at >20 mcg/mL)
Mild (10-20 mcg/mL): Nausea, vomiting, diarrhea, headache, restlessness, insomnia
Moderate-Severe (>20 mcg/mL): Cardiac arrhythmias (tachycardia, ventricular arrhythmias), hypotension
Severe (>40 mcg/mL): Seizures (potentially fatal), ventricular fibrillation
Drug Interactions:
  1. Ciprofloxacin, erythromycin, cimetidine - inhibit CYP1A2 → ↑theophylline levels → toxicity
  2. Rifampicin, phenytoin, carbamazepine, phenobarbitone - induce CYP1A2 → ↓theophylline levels → reduced efficacy
  3. Caffeine + theophylline → additive toxicity
  4. Smoking induces CYP1A2 → ↓theophylline levels
Aminophylline = theophylline + ethylenediamine (makes it water-soluble for IV use). MOA is identical to theophylline. Adverse effects same as theophylline - particularly risk of arrhythmia if given too rapidly IV.

LAQ 3. List the classes of drugs used in the therapy of cough with an example for each class. Write down the mechanism of action of Bromhexine. [3+2=5]

Classes of Drugs Used in Cough Therapy

ClassDrug ExamplesUsed For
Antitussives (Cough suppressants)Codeine, Dextromethorphan, NoscapineDry/non-productive cough
ExpectorantsGuaifenesin, Potassium iodide, Ammonium chlorideProductive cough
MucolyticsBromhexine, Acetylcysteine, AmbroxolProductive cough with viscid sputum
DemulcentsHoney, Glycerol, LinctusSoothe irritated mucosa (mild cough)
AntihistaminesChlorpheniramine, DiphenhydramineCough due to allergic rhinitis
BronchodilatorsSalbutamolCough-variant asthma
AntibioticsAmoxicillin, AzithromycinInfective causes

Mechanism of Action of Bromhexine

Bromhexine is a mucolytic and expectorant derived from the Adhatoda vasica plant alkaloid vasicine.
Mechanism:
  1. Depolymerizes mucopolysaccharide fibers in bronchial secretions - breaks the acid mucopolysaccharide (mucoprotein) fibers that give mucus its viscosity, reducing mucus thickness
  2. Stimulates serous gland secretion in the bronchial mucosa, increasing the watery component of mucus (reducing gel:sol ratio)
  3. Stimulates ciliary activity - facilitates mucociliary clearance
  4. Active metabolite ambroxol also stimulates surfactant production from Type II pneumocytes
Uses: Chronic bronchitis, bronchiectasis, COPD, cystic fibrosis, post-operative pulmonary care
Dose: Oral 8-16 mg three times daily; also available as syrup and inhalation solution
Adverse effects: Mild GI disturbance (nausea, diarrhea); hypersensitivity reactions (rare)

LAQ 4. Difference between Heparin and Warfarin. Write a brief note on uses and adverse effects of Aspirin.

(Note: This question appears to relate to blood/coagulation pharmacology, not respiratory - but answering as written)

Differences Between Heparin and Warfarin

FeatureHeparinWarfarin
NatureLarge molecular weight polysaccharide (biological)Small molecule coumarin derivative (synthetic)
RouteIV or SC only (not oral - not absorbed)Oral
MechanismActivates antithrombin III → inactivates thrombin (IIa), Xa, IXa, XIaInhibits Vitamin K epoxide reductase → blocks synthesis of Vit K-dependent clotting factors (II, VII, IX, X, Protein C, S)
Onset of actionImmediate (IV)Delayed (2-5 days - dependent on existing factor decay)
DurationShort (IV: 4-6h; SC: 8-12h)Long (t1/2 ~35-45 hours)
MonitoringaPTT (activated partial thromboplastin time)PT/INR
AntidoteProtamine sulfateVitamin K; fresh frozen plasma (FFP) for emergency
Crosses placenta?No (safe in pregnancy)Yes (teratogenic - avoid in 1st trimester)
Use in renal failureLMWH requires caution; UFH preferredPreferred
ReversibilityRapidly reversibleSlow reversal with Vitamin K
Main useDVT, PE treatment/prophylaxis; ACS; surgery; dialysisLong-term anticoagulation (AF, mechanical valves, DVT/PE secondary prevention)

Brief Note on Aspirin (Acetylsalicylic Acid)

Class: NSAID; antiplatelet; analgesic; antipyretic; anti-inflammatory
Mechanism: Irreversibly inhibits COX-1 and COX-2 (cyclooxygenase) enzymes by covalent acetylation → reduces prostaglandin and thromboxane A2 (TXA2) synthesis. Low-dose aspirin's antiplatelet effect is due to irreversible inhibition of COX-1 in platelets (which cannot synthesize new COX as they lack nuclei) → ↓TXA2 → reduced platelet aggregation.
Uses:
  1. Analgesic/antipyretic: Headache, fever, mild-moderate pain
  2. Anti-inflammatory: Rheumatoid arthritis, acute rheumatic fever
  3. Antiplatelet (cardioprotective - low dose 75-150 mg/day):
    • Secondary prevention of MI and ischemic stroke
    • Unstable angina, ACS
    • Post-coronary stent/bypass
  4. Kawasaki disease (high dose)
Adverse Effects:
  1. GI: Epigastric pain, nausea, gastric ulceration, GI bleeding (reduced prostaglandin-mediated mucosal protection)
  2. Salicylism (chronic toxicity): Tinnitus, dizziness, headache, hyperventilation, deafness
  3. Reye's syndrome: Avoid in children <12 years with viral infections - associated with hepatic encephalopathy
  4. Hypersensitivity: Aspirin-induced asthma (aspirin-exacerbated respiratory disease - AERD); urticaria - due to shunting of arachidonic acid to leukotriene pathway
  5. Antiplatelet effect: Increases bleeding time; avoid before surgery
  6. Metabolic: High doses cause respiratory alkalosis then metabolic acidosis
  7. Uricosuric/antiuricosuric: Low doses retain uric acid (avoid in gout); high doses are uricosuric
References: Lippincott Illustrated Reviews: Pharmacology; Goodman & Gilman's The Pharmacological Basis of Therapeutics; Harrison's Principles of Internal Medicine 22nd Ed.
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