Pharmacology
MBBS Pharmacology — high-yield long questions and short notes from K.D. Tripathi, covering general pharmacology, autonomic and cardiovascular drugs, CNS, autacoids, chemotherapy, endocrine and more, written to the marks with mechanisms, classification, clinical uses, adverse effects and pearls.
12chapters144questions99High-Yield
Definition
Antimicrobial therapy uses drugs that selectively kill or inhibit microorganisms with minimal harm to the host (selective toxicity).
Classification
- Bactericidal — kill bacteria (penicillins, aminoglycosides)
- Bacteriostatic — inhibit growth (tetracyclines, macrolides)
- Narrow vs broad spectrum
Mechanisms of Action
- Cell-wall synthesis — β-lactams, vancomycin
- Protein synthesis — aminoglycosides, macrolides, tetracyclines
- Nucleic acid synthesis — fluoroquinolones, rifampicin
- Folate synthesis — sulfonamides, trimethoprim
Principles of Use
- Culture and sensitivity before starting (when possible)
- Correct dose and adequate duration
- Avoid unnecessary combinations
- Consider host factors (renal/hepatic function, pregnancy)
Rational choice and full courses cure infection and limit resistance. Mechanism Example Cell wall Penicillin Protein synthesis Gentamicin DNA gyrase Ciprofloxacin Folate Sulfonamide Applied
- Empirical therapy in serious infection
- Antibiotic stewardship limits resistance
🔑KEY POINTS TO REMEMBER- Selective toxicity is the basis of antimicrobial therapy.
- Bactericidal vs bacteriostatic; four main mechanisms.
- Correct dose, duration and stewardship prevent resistance.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
β-lactam antibiotics contain a β-lactam ring and act by inhibiting bacterial cell-wall synthesis; they are bactericidal.
Groups
- Penicillins — penicillin G, amoxicillin, piperacillin
- Cephalosporins — five generations
- Carbapenems — imipenem, meropenem
- Monobactams — aztreonam
Mechanism
- Bind penicillin-binding proteins (transpeptidases)
- Inhibit peptidoglycan cross-linking
- Cell wall weakens → lysis (bactericidal)
Resistance
- β-lactamase production (main mechanism)
- Overcome by inhibitors: clavulanic acid, sulbactam, tazobactam
Blocking cross-linking leaves a fragile wall, and the bacterium bursts. Group Example Note Penicillin Amoxicillin Broad spectrum Cephalosporin Ceftriaxone 3rd generation Carbapenem Meropenem Reserve drug Applied
- Hypersensitivity (rash to anaphylaxis)
- Amoxicillin-clavulanate resists β-lactamase
🔑KEY POINTS TO REMEMBER- β-lactams inhibit cell-wall cross-linking → bactericidal.
- Groups: penicillins, cephalosporins, carbapenems, monobactams.
- β-lactamase resistance countered by clavulanic acid.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Aminoglycosides are bactericidal antibiotics that inhibit protein synthesis by binding the 30S ribosomal subunit.
Drugs & Mechanism
- Gentamicin, amikacin, streptomycin, tobramycin, neomycin
- Bind 30S subunit → misreading of mRNA
- Bactericidal, concentration-dependent killing
- Active against aerobic Gram-negative bacilli
- Not absorbed orally (given parenterally)
Adverse Effects
- Nephrotoxicity (reversible)
- Ototoxicity (often irreversible)
- Neuromuscular blockade
Ribosomal misreading produces defective proteins that kill the bacterium. Drug Use Gentamicin Gram-negative sepsis Amikacin Resistant organisms Streptomycin Tuberculosis Applied
- Once-daily dosing reduces toxicity
- Monitor renal function and levels
🔑KEY POINTS TO REMEMBER- Aminoglycosides bind the 30S subunit → bactericidal.
- Effective against aerobic Gram-negative bacilli; not orally absorbed.
- Adverse: nephrotoxicity, ototoxicity, neuromuscular blockade.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Macrolides and tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit bacterial protein synthesis.
Macrolides
- Erythromycin, azithromycin, clarithromycin
- Bind 50S subunit → block translocation
- Uses: atypical pneumonia, diphtheria, whooping cough, penicillin allergy
- Adverse: gastrointestinal upset, enzyme inhibition (erythromycin)
Tetracyclines
- Doxycycline, tetracycline, minocycline
- Bind 30S subunit → block tRNA binding
- Uses: rickettsia, chlamydia, cholera, acne, brucellosis
- Adverse: tooth discoloration, avoid in children and pregnancy
Both stop protein synthesis but bind different ribosomal subunits. Group Subunit Key use Macrolide 50S Atypical pneumonia Tetracycline 30S Rickettsia, chlamydia Applied
- Azithromycin — single-dose therapy (long half-life)
- Tetracyclines chelate calcium (avoid with milk, antacids)
🔑KEY POINTS TO REMEMBER- Macrolides bind 50S; tetracyclines bind 30S — both bacteriostatic.
- Macrolides for atypical pneumonia and penicillin-allergic patients.
- Tetracyclines contraindicated in children and pregnancy.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Fluoroquinolones inhibit bacterial DNA gyrase, while sulfonamides block folate synthesis — both are widely used antibacterials.
Fluoroquinolones
- Ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin
- Inhibit DNA gyrase (topoisomerase II) — bactericidal
- Uses: urinary tract infection, typhoid, gonorrhoea, respiratory infections
- Adverse: tendon rupture, QT prolongation; avoid in children
Sulfonamides
- Sulfamethoxazole, sulfadiazine
- Inhibit dihydropteroate synthase (folate synthesis)
- Bacteriostatic; synergistic with trimethoprim
- Adverse: rash, Stevens-Johnson syndrome, crystalluria
One halts DNA replication; the other starves bacteria of folate. Group Target Type Fluoroquinolone DNA gyrase Bactericidal Sulfonamide Folate pathway Bacteriostatic Applied
- Ciprofloxacin — first-line for many urinary infections
- Co-trimoxazole in Pneumocystis pneumonia
🔑KEY POINTS TO REMEMBER- Fluoroquinolones inhibit DNA gyrase — bactericidal.
- Sulfonamides block folate synthesis — bacteriostatic.
- Quinolones: tendon rupture, avoid in children.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Antimicrobial resistance is the ability of microorganisms to survive exposure to drugs that would normally kill or inhibit them.
Mechanisms
- Enzymatic inactivation — β-lactamase
- Altered target — modified penicillin-binding protein (MRSA)
- Reduced uptake / efflux pumps
- Alternative metabolic pathway
Causes & Prevention
- Irrational and incomplete antibiotic use
- Over-the-counter availability, agricultural use
- Prevention: culture-guided therapy, full course, stewardship, infection control
Antibiotic pressure selects resistant strains, which then spread their genes. Mechanism Example Enzyme β-lactamase Altered target MRSA Efflux Tetracycline resistance Applied
- MRSA, ESBL, multidrug-resistant tuberculosis
- Antibiotic stewardship programmes
🔑KEY POINTS TO REMEMBER- Resistance mechanisms: enzymes, altered target, efflux, bypass pathways.
- Driven by irrational and incomplete antibiotic use.
- Prevented by stewardship and full courses.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Vancomycin is a glycopeptide antibiotic that inhibits cell-wall synthesis and is reserved for resistant Gram-positive infections.
Mechanism & Spectrum
- Binds D-alanyl-D-alanine → blocks peptidoglycan synthesis
- Bactericidal; Gram-positive only
- Not absorbed orally (given IV for systemic infection)
- Oral form used for Clostridioides difficile colitis
Uses & Adverse Effects
- MRSA infections
- Serious Gram-positive sepsis, endocarditis
- Adverse: red man syndrome (rapid infusion), nephrotoxicity, ototoxicity
By capping the wall precursor, vancomycin halts peptidoglycan assembly. Feature Detail Spectrum Gram-positive Key use MRSA Adverse Red man syndrome Applied
- Infuse slowly to avoid red man syndrome
- Monitor levels and renal function
🔑KEY POINTS TO REMEMBER- Vancomycin blocks cell-wall synthesis (binds D-ala-D-ala).
- Reserved for MRSA and serious Gram-positive infection.
- Red man syndrome with rapid infusion; oral form for C. difficile.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Metronidazole is a nitroimidazole active against anaerobic bacteria and protozoa.
Mechanism & Spectrum
- Reduced inside anaerobes → reactive intermediates
- Damage microbial DNA → cell death
- Active only where anaerobic reduction occurs
- Covers anaerobes, Entamoeba, Giardia, Trichomonas
Uses & Adverse Effects
- Amoebiasis, giardiasis, trichomoniasis
- Anaerobic infections, bacterial vaginosis
- C. difficile colitis, H. pylori regimens
- Adverse: metallic taste, nausea, disulfiram-like reaction with alcohol
Only anaerobic organisms can activate the drug, giving its selectivity. Target Example Anaerobes Bacteroides Protozoa Entamoeba, Giardia Applied
- Avoid alcohol during and after treatment
- Peripheral neuropathy with prolonged use
🔑KEY POINTS TO REMEMBER- Metronidazole is activated inside anaerobes → DNA damage.
- Covers anaerobes and protozoa (amoebiasis, giardiasis, trichomoniasis).
- Disulfiram-like reaction with alcohol.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Chloramphenicol is a broad-spectrum bacteriostatic antibiotic that inhibits protein synthesis at the 50S ribosomal subunit.
Mechanism & Features
- Binds 50S → inhibits peptidyl transferase
- Broad spectrum, good CNS penetration
- Well absorbed orally
Uses & Toxicity
- Enteric fever (reserve), bacterial meningitis (alternative)
- Topical for eye infections
- Aplastic anaemia (rare, irreversible, dose-independent)
- Grey baby syndrome in neonates (immature conjugation)
Blocking peptide bond formation halts bacterial protein synthesis. Toxicity Feature Aplastic anaemia Rare, irreversible Grey baby syndrome Neonates Applied
- Restricted use because of marrow toxicity
- Safe topically (eye drops)
🔑KEY POINTS TO REMEMBER- Chloramphenicol binds 50S (inhibits peptidyl transferase).
- Broad spectrum with good CNS penetration.
- Toxicity: aplastic anaemia, grey baby syndrome.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Cephalosporins are β-lactam antibiotics classified into generations with progressively greater Gram-negative activity.
Generations
- First — cefazolin, cephalexin (Gram-positive; surgical prophylaxis)
- Second — cefuroxime (mixed)
- Third — ceftriaxone, cefotaxime (Gram-negative, CNS penetration)
- Fourth — cefepime (broad, antipseudomonal)
- Fifth — ceftaroline (covers MRSA)
Mechanism & Adverse Effects
- Inhibit cell-wall synthesis (bactericidal)
- Adverse: hypersensitivity, diarrhoea
- Cross-reactivity with penicillin allergy (~5–10%)
Moving up the generations trades Gram-positive for Gram-negative cover. Generation Example Strength 1st Cefazolin Gram-positive 3rd Ceftriaxone Gram-negative, CNS 5th Ceftaroline MRSA Applied
- Ceftriaxone for meningitis, enteric fever, gonorrhoea
- Cefazolin for surgical prophylaxis
🔑KEY POINTS TO REMEMBER- Cephalosporins are bactericidal β-lactams in five generations.
- Higher generations → more Gram-negative and CNS penetration.
- Cross-reactivity with penicillin allergy.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Co-trimoxazole is a fixed-dose combination of trimethoprim and sulfamethoxazole that blocks two sequential steps of folate synthesis.
Mechanism (sequential blockade)
- Sulfamethoxazole → inhibits dihydropteroate synthase
- Trimethoprim → inhibits dihydrofolate reductase
- Synergistic → bactericidal (though each alone is bacteriostatic)
Uses & Adverse Effects
- Pneumocystis jirovecii pneumonia (drug of choice)
- Urinary tract infection, nocardiosis, toxoplasmosis
- Adverse: rash, Stevens-Johnson syndrome, megaloblastic anaemia, hyperkalaemia
Blocking two consecutive steps produces powerful synergistic killing. Component Enzyme inhibited Sulfamethoxazole Dihydropteroate synthase Trimethoprim Dihydrofolate reductase Applied
- Prophylaxis in HIV (Pneumocystis)
- Avoid in pregnancy and G6PD deficiency
🔑KEY POINTS TO REMEMBER- Co-trimoxazole = trimethoprim + sulfamethoxazole (sequential blockade).
- Synergistic and bactericidal.
- Drug of choice for Pneumocystis pneumonia.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Penicillin hypersensitivity is an immune-mediated adverse reaction to penicillins, ranging from rash to fatal anaphylaxis.
Types of Reaction
- Immediate (Type I, IgE) — anaphylaxis, urticaria, bronchospasm (minutes)
- Accelerated — 1–72 hours (urticaria)
- Delayed — rash, serum sickness, Stevens-Johnson syndrome
Prevention & Management
- Detailed drug-allergy history before prescribing
- Skin testing where available; keep resuscitation ready
- Anaphylaxis — adrenaline IM (first-line), oxygen, fluids, hydrocortisone, antihistamine
- Use alternatives: macrolides, clindamycin
Sensitised mast cells degranulate on re-exposure, causing anaphylaxis. Reaction Onset Treatment Anaphylaxis Minutes Adrenaline IM Rash Days Stop drug Applied
- Cross-reactivity with cephalosporins (~5–10%)
- Always record the allergy in the case notes
🔑KEY POINTS TO REMEMBER- Penicillin allergy: immediate (IgE), accelerated, delayed types.
- Anaphylaxis treated with IM adrenaline first.
- Cross-reactivity with cephalosporins; use macrolides instead.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.