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GENERAL PHARMACOLOGICAL PRINCIPLES

BDS 1st Year | Kathmandu University | Board Exam Answers

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LONG ANSWER QUESTIONS (LAQs)

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Q1. Define bioavailability. Explain the different factors affecting drug absorption. [1+4=5]

Definition of Bioavailability

• For an IV drug: bioavailability = 100% (F = 1)
• For oral drugs: F < 1 due to incomplete absorption and first-pass metabolism

Factors Affecting Drug Absorption

1. Lipid solubility: Drugs must be sufficiently lipophilic to cross lipid membranes. Highly hydrophilic drugs are poorly absorbed; extremely lipophilic drugs are also poorly absorbed because they cannot dissolve in aqueous body fluids. Weak acids and weak bases are best absorbed.
2. Degree of ionization (Henderson-Hasselbalch): Only the non-ionized (un-charged) form of a drug crosses membranes. Weak acids (e.g., aspirin, pKa ~3.5) are non-ionized in the acidic stomach and are absorbed there. Weak bases are non-ionized in the alkaline intestine.
3. Molecular size: Smaller molecules diffuse more easily across membranes.
4. Drug formulation: Particle size, salt form, crystal polymorphism, enteric coatings, binders, and excipients influence dissolution rate and absorption.
5. Chemical instability: Penicillin G is degraded by gastric acid; insulin is destroyed by GI proteases.

1. Gastric pH: Acidic pH inactivates acid-labile drugs (e.g., erythromycin). pH also determines the ionization state of the drug.
2. Gastric emptying time: Faster emptying increases delivery to the intestine (main absorption site), speeding absorption of most drugs.
3. GI motility: Increased motility reduces contact time with the absorptive surface; decreased motility can increase absorption.
4. Surface area: The small intestine has a large surface area (villi, microvilli), making it the primary site of drug absorption.
5. Blood flow to the absorption site: Greater blood flow maintains the concentration gradient, favoring absorption.
6. First-pass metabolism: After oral absorption, drugs pass through the portal circulation to the liver before reaching systemic circulation. Extensive hepatic metabolism significantly reduces bioavailability (e.g., morphine, propranolol, lidocaine, nitroglycerin).
7. Food: Food can delay gastric emptying, bind drugs, or alter pH - affecting absorption.
8. Age: Neonates and elderly have altered gastric pH and motility.

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Q2. Short Notes on:

(a) Therapeutic Drug Monitoring (TDM)

• Drugs with a narrow therapeutic index (e.g., digoxin, lithium, phenytoin, aminoglycosides, cyclosporine)
• Suspected toxicity or treatment failure
• Altered pharmacokinetics (renal/hepatic disease, pregnancy)
• Suspected non-compliance

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(b) First-Pass Metabolism (Pre-Systemic Metabolism)

• Nitroglycerin is given sublingually to bypass first-pass metabolism
• Oral bioavailability of propranolol is only ~25% due to first-pass effect
• Some drugs are given in higher oral doses to compensate

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(c) Nomenclature of Drugs with Examples

1. Chemical name: Describes exact chemical structure (e.g., N-acetyl-para-aminophenol)
2. Generic (non-proprietary/INN) name: Internationally recognized official name (e.g., paracetamol/acetaminophen)
3. Brand/Trade (proprietary) name: Given by the manufacturer (e.g., Calpol, Tylenol)

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(d) Adverse Drug Reactions (ADR) with Examples

• Type A (Augmented/Predictable): Dose-related, predictable from pharmacology. Most common (80%). E.g., hypoglycemia with insulin, gastric ulcer with NSAIDs.
• Type B (Bizarre/Unpredictable): Not dose-related, idiosyncratic. E.g., anaphylaxis with penicillin, agranulocytosis with clozapine.
• Type C (Chronic): Related to cumulative dose. E.g., adrenal suppression with long-term corticosteroids.
• Type D (Delayed): Appear after long latency. E.g., carcinogenesis with alkylating agents.
• Type E (End-of-use/Withdrawal): Occur after stopping the drug. E.g., withdrawal seizures with benzodiazepines.

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(e) Antagonist

1. Competitive antagonist: Competes reversibly with agonist at the same receptor site; effect overcome by increasing agonist dose (e.g., atropine blocks muscarinic receptors).
2. Non-competitive antagonist: Binds irreversibly or at different site; effect cannot be overcome by increasing agonist dose (e.g., phenoxybenzamine).
3. Physiological antagonist: Acts at a different receptor to produce opposite effect (e.g., adrenaline and histamine).
4. Chemical antagonist: Inactivates the agonist chemically (e.g., protamine neutralizes heparin).

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(f) Superinfection

• Oral broad-spectrum antibiotics (e.g., tetracycline, ampicillin) suppress normal bowel flora, allowing overgrowth of Candida albicans (oral/vaginal thrush) or Clostridioides difficile (pseudomembranous colitis).

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(g) Agonist and Antagonist

• Agonist: A drug that binds to a receptor and activates it, producing a biological response. Has both affinity (binds receptor) and intrinsic activity (efficacy). Example: morphine (opioid receptor agonist), salbutamol (beta-2 agonist).
• Antagonist: A drug that binds receptor but produces no intrinsic activity; blocks agonist effect. Example: naloxone (opioid antagonist), propranolol (beta-blocker).
• Partial agonist: Has affinity and some intrinsic activity, but less than a full agonist. Can act as antagonist in presence of full agonist. Example: buprenorphine.

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(h) Drug Dependence

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(i) Plasma Half-Life and Its Importance

1. Determines dosing frequency - drugs with short t1/2 need more frequent dosing
2. Time to steady state = 4-5 half-lives
3. Time for drug to be eliminated from body = 4-5 half-lives
4. Guides loading dose calculation
5. Useful in TDM and predicting drug accumulation
6. Determines duration of action (in many cases)

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(j) GPCR (G-protein coupled receptors) and Adverse Drug Reactions

• Beta-2 agonists (salbutamol) via Gs-cAMP - cause tachycardia, tremor
• Opioids via Gi - cause respiratory depression, constipation
• Muscarinic agonists via Gq - cause excessive secretions, bradycardia

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Q3. List different routes of drug administration with an example of each. Write two advantages and two disadvantages of the sublingual route. [4+2=6]

Routes of Drug Administration

Sublingual Route - Advantages

1. Rapid onset of action - drug is directly absorbed into venous drainage of the tongue and enters systemic circulation rapidly (e.g., GTN acts within 1-2 minutes in angina)
2. Avoidance of first-pass metabolism - drug bypasses the portal circulation and liver, resulting in higher bioavailability than the oral route

Sublingual Route - Disadvantages

1. Only small doses can be administered - limited by absorptive surface area and the volume of drug that can be placed under the tongue
2. Short duration - saliva production may wash away drug; the patient must not swallow; not suitable for drugs requiring sustained release

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Q4. Define drug absorption. Enlist various factors affecting drug absorption. [1+4=5]

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Q5. Define Biotransformation. Describe Phase I reaction. [1+4=5]

Definition

Phase I Reactions (Functionalization Reactions)

• Located in the smooth endoplasmic reticulum of hepatocytes
• Multiple isoforms: CYP3A4 (most common), CYP2D6, CYP2C9, CYP1A2
• CYP3A4 metabolizes ~50% of all drugs (e.g., erythromycin, nifedipine, simvastatin)

1. Oxidation (most common):
   • Aliphatic hydroxylation, aromatic hydroxylation, N-dealkylation, O-dealkylation, S-oxidation
   • Example: Diazepam is oxidized to active metabolite desmethyldiazepam
   • Phenytoin undergoes aromatic hydroxylation
2. Reduction:
   • Nitro reduction (e.g., chloramphenicol), carbonyl reduction (e.g., haloperidol)
3. Hydrolysis:
   • Ester hydrolysis: aspirin is hydrolyzed to salicylic acid in the liver
   • Amide hydrolysis: procainamide, lidocaine

• May produce an active metabolite (codeine → morphine)
• May produce a toxic metabolite (paracetamol → NAPQI at high doses)
• Prepares molecule for Phase II conjugation

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Q6. Advantages and Disadvantages of Oral, Parenteral, and Intravenous Routes [8]

Oral Route

Parenteral Route (IM/SC)

Intravenous (IV) Route

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Q7. Define Bioavailability and Bioequivalence. Mention the clinical significance of therapeutic half-life. [2+1]

Bioavailability

Bioequivalence

1. Comparable bioavailability (AUC - area under curve)
2. Similar rate of absorption (similar Cmax and Tmax)

• This is important for generic drug substitution - a generic is considered therapeutically equivalent to the brand if it is bioequivalent.

Clinical Significance of Therapeutic Half-Life

1. Dosing frequency: Short t1/2 drugs need more frequent dosing (morphine q4h); long t1/2 drugs can be dosed once daily (amlodipine)
2. Time to steady state: Reached in 4-5 half-lives
3. Drug accumulation: Drugs with long t1/2 accumulate with repeated dosing
4. Duration of action: Guides how long an effect lasts after stopping
5. Dose adjustment in renal/hepatic impairment: t1/2 increases, requiring dose reduction

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Q8. Define Pharmacokinetics and Pharmacodynamics. Discuss any four major factors affecting drug response. [1+1+4=6]

Pharmacokinetics (PK)

Pharmacodynamics (PD)

Four Major Factors Affecting Drug Response

1. Age:
   • Neonates and infants: immature liver enzymes, altered renal clearance, higher Vd for water-soluble drugs; require dose reduction
   • Elderly: reduced hepatic and renal function, reduced plasma albumin, polypharmacy and drug interactions, altered body composition
2. Genetics (Pharmacogenetics):
   • Genetic polymorphisms in drug-metabolizing enzymes alter response
   • CYP2D6 poor metabolizers accumulate codeine; ultra-rapid metabolizers may suffer codeine toxicity
   • G6PD deficiency: hemolysis with primaquine
   • Slow vs. fast acetylators: INH toxicity in slow acetylators
3. Disease States:
   • Liver disease: reduced first-pass metabolism, reduced plasma protein synthesis (less protein binding) - increase in free drug
   • Renal disease: reduced excretion of renally-eliminated drugs (e.g., aminoglycosides, digoxin) - risk of toxicity
   • Heart failure: reduced cardiac output reduces hepatic blood flow
4. Drug Interactions:
   • Pharmacokinetic interactions: one drug alters the ADME of another (e.g., rifampicin induces CYP450, reducing efficacy of oral contraceptives)
   • Pharmacodynamic interactions: additive (aspirin + heparin - increased bleeding), synergistic (alcohol + benzodiazepine - CNS depression), antagonistic (naloxone reverses morphine)

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Q9. Explain various types of drug antagonism with suitable examples. [1+1+4=6]

Definition of Antagonism

Types of Drug Antagonism

• Antagonist and agonist compete for the same receptor binding site
• Antagonist has affinity but zero intrinsic activity
• Effect can be overcome by increasing agonist concentration (parallel rightward shift of dose-response curve with no change in maximum response)
• Example: Atropine competitively blocks acetylcholine at muscarinic receptors; propranolol competitively blocks adrenaline at beta-adrenergic receptors; naloxone blocks morphine at opioid receptors

• Antagonist binds irreversibly to the receptor or to an allosteric site (different from agonist binding site)
• Effect cannot be overcome by increasing agonist concentration (depresses maximum response; shifts dose-response curve downward)
• Example: Phenoxybenzamine irreversibly blocks alpha-adrenergic receptors; aspirin irreversibly inhibits COX enzyme

• Two drugs act on different receptors but produce opposite physiological effects, thereby canceling each other
• Example: Histamine causes bronchoconstriction (H1 receptor); adrenaline causes bronchodilation (beta-2 receptor). Adrenaline is the physiological antagonist of histamine in anaphylaxis.
• Another example: Insulin lowers blood glucose; glucagon raises blood glucose.

• Antagonist directly reacts chemically with the agonist, inactivating it (not receptor-mediated)
• Example:
  • Protamine sulfate neutralizes heparin (ionic interaction)
  • Dimercaprol (BAL) chelates heavy metal ions (arsenic, mercury)
  • Activated charcoal adsorbs many drugs in overdose

• One drug reduces the effective concentration of another by altering its ADME
• Example:
  • Rifampicin induces CYP450 enzymes, increasing metabolism of oral contraceptives - reduces their efficacy
  • Antacids reduce absorption of tetracycline by forming chelates

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SHORT ANSWER QUESTIONS (SAQs)

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SAQ 1. Enterohepatic Circulation

1. Drug absorbed from gut enters liver via portal vein
2. Liver conjugates drug (glucuronidation) and secretes conjugate into bile
3. Bile enters small intestine
4. Intestinal bacteria produce beta-glucuronidase enzyme, which cleaves the conjugate, releasing free drug
5. Free drug is reabsorbed from the intestine into the portal vein and recycled

• Prolongs drug action and half-life (e.g., morphine, estrogens, oral contraceptives, digoxin)
• Interruption by antibiotics (killing gut flora) can reduce efficacy of oral contraceptives
• Cholestyramine can interrupt enterohepatic cycling by binding drugs in the gut

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SAQ 2. Agonist and Antagonist

• Full agonist (e.g., morphine, salbutamol) - produces maximum response
• Partial agonist (e.g., buprenorphine) - produces submaximal response

• Competitive (e.g., naloxone, atropine, propranolol)
• Non-competitive (e.g., phenoxybenzamine)

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SAQ 3. Fluconazole

• Oropharyngeal and esophageal candidiasis (common in HIV patients)
• Vulvovaginal candidiasis
• Cryptococcal meningitis (maintenance therapy)
• Prophylaxis in immunocompromised patients
• Tinea infections

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SAQ 4. Propranolol

• Heart: Reduces heart rate (negative chronotropy), conduction velocity (negative dromotropy), and contractility (negative inotropy) via beta-1 blockade
• Bronchi: Bronchoconstriction via beta-2 blockade (dangerous in asthma)
• Antihypertensive: Reduces cardiac output; reduces renin release

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SAQ 5. Pralidoxime (2-PAM)

• Organophosphate poisoning (used alongside atropine)
• Atropine treats the muscarinic effects (SLUDGE - Salivation, Lacrimation, Urination, Defecation, GI cramping, Emesis)
• Pralidoxime treats nicotinic effects (muscle weakness, paralysis) and regenerates enzyme

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SAQ 6. Advantages of Atenolol over Propranolol

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SAQ 7. Types of Antagonism

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Summary of All Answers Covered

LAQs (Long Answer Questions)

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

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RESPIRATORY SYSTEM - PHARMACOLOGY

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

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SHORT NOTES (5 Marks Each)

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1. Use of Salbutamol 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

• Tremor (most common - hands), palpitations, tachycardia (beta-1 spillover at high doses)
• Hypokalemia (K+ shift into cells)
• Headache, nervousness, hyperglycemia

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2. Combination Therapy in Tuberculosis

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

• Written as: 2HRZE

• Written as: 4HR

• 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

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3. First-Line Antitubercular Drugs

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4. Bronchodilators

• 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

• Theophylline, Aminophylline
• MOA: Non-selective PDE inhibition → ↑cAMP; adenosine receptor antagonism; anti-inflammatory
• Narrow therapeutic index; requires TDM

• 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

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5. Mucolytics

• 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).

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6. Drugs Used in Productive Cough

• Guaifenesin: Most widely used; stimulates bronchial secretions by reflex action
• Potassium iodide: Stimulates bronchial gland secretion
• Steam inhalation: Humidifies secretions

• Antibiotics if bacterial infection (pneumonia, bronchitis)
• Bronchodilators if bronchoconstriction present

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7. Expectorants

• 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

• Directly stimulate bronchial glands
• Examples: Potassium iodide (high doses), Creosote, Terpin hydrate

• Menthol, Eucalyptus oil, Turpentine oil - soothing effect; mild expectorant

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8. Sodium Cromoglycate (Cromolyn Sodium)

• Also inhibits early and late phase allergic responses
• May inhibit eosinophil and neutrophil activation
• Does NOT have bronchodilator activity

• 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

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)

• Local: throat irritation, cough, bronchospasm (paradoxical - rare)
• Headache
• Safe in pregnancy and children

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LONG ANSWER QUESTIONS (LAQs)

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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)

• 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

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)

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

Rationale of Combination Therapy

• 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

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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

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)

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)

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Mechanism of Action of Theophylline

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

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)

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

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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

Mechanism of Action of Bromhexine

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

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

Differences Between Heparin and Warfarin

Brief Note on Aspirin (Acetylsalicylic Acid)

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)

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

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