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2nd Year MBBS Pharmacology - Complete Exam Notes

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1. TUBERCULOSIS (Anti-TB Drugs)

First-Line Drugs - Mnemonic: "RIPE" (or RIPES)

Treatment Regimens (RNTCP/WHO)

• New TB: 2HRZE / 4HR
  • 2 months Intensive phase: H+R+Z+E
  • 4 months Continuation phase: H+R
• MDR-TB: Resistant to at least INH + Rifampicin - use Bedaquiline, Linezolid, Clofazimine
• XDR-TB: MDR + resistant to fluoroquinolones + injectable agents

Key Points for Exam:

• INH is bactericidal - acts only on actively dividing bacilli
• Rifampicin - broadest anti-TB activity; also induces CYP450 (reduces OCP efficacy)
• Pyrazinamide acts in acidic pH - kills intracellular bacilli
• Ethambutol is bacteriostatic
• Slow vs Fast acetylators matter for INH toxicity (slow acetylators = more toxicity)

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2. MALARIA (Anti-malarials)

Life Cycle Targets - Mnemonic: "CQPAM"

Key Points for Exam:

• Chloroquine - drug of choice for P. vivax; CQ resistance common in P. falciparum
• Primaquine - only drug acting on hypnozoites (dormant liver forms) - must rule out G6PD deficiency first (causes hemolytic anemia)
• Artemisinin Combination Therapy (ACT) = Artemether + Lumefantrine - first line for uncomplicated P. falciparum
• Quinine = drug of choice for severe malaria (IV); also used in pregnancy
• Blackwater fever = massive hemolysis + hemoglobinuria - associated with quinine/falciparum
• Cinchonism = tinnitus + headache + visual disturbance (quinine toxicity)

Prophylaxis:

• Chloroquine-sensitive areas: Chloroquine weekly
• Resistant areas: Mefloquine / Doxycycline / Atovaquone-proguanil

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3. BETA-LACTAM ANTIBIOTICS

Mechanism (ONE LINE): Inhibit transpeptidase (PBP - Penicillin Binding Protein) → block cross-linking of peptidoglycan → bactericidal

Classes:

1. Penicillins
2. Cephalosporins
3. Carbapenems
4. Monobactams

Resistance Mechanism:

• Beta-lactamase enzyme (penicillinase) hydrolyzes beta-lactam ring
• Solution: Add beta-lactamase inhibitors - Clavulanic acid, Sulbactam, Tazobactam

Beta-lactamase inhibitors + Penicillin combinations:

• Amoxicillin + Clavulanic acid (Co-amoxiclav / Augmentin)
• Ampicillin + Sulbactam
• Piperacillin + Tazobactam

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4. CEPHALOSPORINS

Generations - Mnemonic: "Generations improve gram-negative coverage"

Key Points for Exam:

• Ceftriaxone - longest half-life (once daily dosing), drug of choice for gonorrhea and meningitis
• Ceftazidime - best anti-Pseudomonal cephalosporin (3rd gen)
• 10% cross-reactivity with penicillin allergy (use with caution)
• Cephalosporins do NOT cover: Listeria, Enterococcus, MRSA (except 5th gen), atypicals
• Cefaclor - 2nd gen oral cephalosporin (serum-sickness-like reaction)

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5. FLUOROQUINOLONES

Mechanism: Inhibit DNA gyrase (Topoisomerase II) in bacteria → prevents DNA supercoiling/replication → bactericidal

• In gram-positive bacteria: primarily inhibit Topoisomerase IV
• In gram-negative bacteria: primarily inhibit DNA gyrase

Classification:

Key Points for Exam:

• Ciprofloxacin - best Pseudomonal coverage among fluoroquinolones
• Levofloxacin + Moxifloxacin = "Respiratory fluoroquinolones" (good for community-acquired pneumonia, atypicals)
• Moxifloxacin = used in MDR-TB
• Side effects: Tendinitis/tendon rupture (especially Achilles), photosensitivity, QT prolongation, cartilage damage (avoid in children/pregnancy), CNS seizures (lowers seizure threshold)
• Contraindicated in: Children (cartilage toxicity), pregnancy, lactation
• Absorption reduced by antacids (Ca2+, Mg2+, Al3+ chelation) - take 2 hours apart

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6. AMINOGLYCOSIDES

Mechanism: Bind 30S ribosomal subunit → misreading of mRNA → faulty protein synthesis → bactericidal (concentration-dependent killing)

Drugs: Streptomycin, Gentamicin, Tobramycin, Amikacin, Neomycin, Kanamycin

Key Points for Exam:

• Concentration-dependent killing - once-daily dosing preferred (peak-dependent efficacy, post-antibiotic effect)
• Synergism with beta-lactams - classic combination (e.g., UTI, bacterial endocarditis)
• Poorly absorbed orally - always given parenterally (IV/IM), except Neomycin (bowel prep only)
• Coverage: Aerobic Gram-negative bacilli (E. coli, Klebsiella, Pseudomonas) + Mycobacteria (Streptomycin for TB)

Toxicity - Mnemonic: "ONN"

• Ototoxicity - cochleotoxicity (Neomycin, Amikacin) + vestibulotoxicity (Gentamicin, Streptomycin)
• Nephrotoxicity - proximal tubular damage (reversible usually); Gentamicin most nephrotoxic
• Neuromuscular blockade - can cause respiratory paralysis (especially in myasthenia gravis)
• Monitoring: Trough levels (nephrotoxicity), Peak levels (efficacy)

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7. HIV POST-EXPOSURE PROPHYLAXIS (PEP)

Definition: Antiretroviral therapy started AFTER potential HIV exposure to prevent infection

When to give:

• Occupational PEP: Needlestick/sharps injury with HIV-positive blood
• Non-occupational PEP: Unprotected sexual exposure, sharing needles

Key Rules:

• Start within 72 hours of exposure (ideally within 2 hours)
• Duration: 28 days
• Efficacy: ~80% reduction in transmission risk

Recommended Regimen (WHO/NACO guidelines):

• TDF = Nucleoside Reverse Transcriptase Inhibitor (NRTI)
• 3TC = NRTI
• DTG = Integrase Strand Transfer Inhibitor (INSTI)

Alternative: TDF + 3TC + Lopinavir/ritonavir (LPV/r)

Post-exposure steps:

1. Wash wound with soap and water (do NOT squeeze/suck)
2. Report to occupational health immediately
3. Test baseline HIV status of exposed person
4. Start PEP within 72 hours
5. Follow-up HIV test at 6 weeks, 3 months, 6 months

Classes of ARVs (exam favorite):

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8. METRONIDAZOLE

Mechanism: Prodrug - reduced intracellularly to toxic free radicals → damages DNA → bactericidal

Spectrum:

• Anaerobic bacteria (Bacteroides, Clostridium, Peptostreptococcus)
• Protozoa: Entamoeba histolytica, Giardia, Trichomonas vaginalis

Key Uses:

Side Effects:

• Metallic taste (most common)
• Disulfiram-like reaction with alcohol (flushing, vomiting) - NEVER consume alcohol
• Peripheral neuropathy (prolonged use)
• Nausea, GI upset
• Dark/brown urine
• CNS: headache, ataxia (high doses)

Contraindicated: First trimester of pregnancy, alcohol consumption

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9. COTRIMOXAZOLE (Trimethoprim + Sulfamethoxazole = TMP-SMX)

Mechanism: Sequential blockade of folate synthesis

• Sulfamethoxazole inhibits dihydropteroate synthase (DHPS) → blocks conversion of PABA to dihydrofolic acid
• Trimethoprim inhibits dihydrofolate reductase (DHFR) → blocks conversion of dihydrofolic acid to tetrahydrofolic acid (THF)

Uses - Mnemonic: "PUCTS"

• Pneumocystis jirovecii pneumonia (PCP) - drug of choice for treatment AND prophylaxis in HIV
• UTI (uncomplicated)
• Cholera (alternative)
• Typhoid (alternative)
• Shigella dysentery
• Also: Nocardia, Toxoplasma (prophylaxis in HIV), Listeria

Side Effects:

• Folate deficiency → megaloblastic anemia, leukopenia
• Hypersensitivity/Stevens-Johnson syndrome (severe)
• Kernicterus in newborns (avoid in last trimester, newborns)
• Hyperkalemia (TMP blocks K+ secretion)
• Crystalluria (sulfonamide component)
• Hemolytic anemia in G6PD deficiency

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10. SULFONAMIDES

Mechanism: Structural analogue of PABA → competitively inhibits dihydropteroate synthase (DHPS) → blocks folate synthesis → bacteriostatic

Classification:

Key Side Effects (Mnemonic "CLASH"):

• Crystalluria (drink plenty of water, alkalinize urine)
• Liver damage (hepatotoxicity)
• Agranulocytosis / Aplastic anemia (hematologic)
• SJS / Hypersensitivity
• Hemolytic anemia (G6PD deficiency)
• Also: Kernicterus in neonates (displaces bilirubin from albumin)

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11. FACTORS RESPONSIBLE FOR FAILURE OF ANTIBIOTICS

Mnemonic: "PRADS - DHIB"

A. Drug-Related Factors:

1. Wrong drug - incorrect antibiotic choice for the organism
2. Wrong dose - sub-therapeutic dosing
3. Wrong route - oral when IV needed (poor bioavailability)
4. Wrong duration - stopping too early
5. Drug interactions - e.g., antacids reducing fluoroquinolone absorption
6. Poor penetration - drug can't reach site (abscess, meningitis, bone)

B. Patient-Related Factors:

1. Non-compliance - patient stops drug early
2. Immunocompromised state - HIV, diabetes, cancer, steroids
3. Pharmacokinetic changes - renal/hepatic failure altering drug levels
4. Malabsorption - reduced oral drug absorption
5. Allergy - drug changed/stopped

C. Organism-Related Factors (most important!):

1. Intrinsic resistance - natural resistance (e.g., gram-negatives resistant to vancomycin)
2. Acquired resistance mechanisms:
   • Beta-lactamase production (destroys beta-lactam ring)
   • Altered target (PBP) - MRSA (altered PBP2a)
   • Efflux pumps - pump drug out of cell (fluoroquinolone resistance)
   • Reduced permeability - porins lost (Pseudomonas)
   • Enzymatic inactivation - acetylation/phosphorylation of aminoglycosides
   • Altered 30S subunit (ribosomal methylation - aminoglycoside resistance)
3. Biofilm formation - Pseudomonas, Staph (prosthetic devices)
4. Intracellular organisms - beta-lactams can't reach intracellular pathogens
5. Superinfection/secondary infection - new resistant organism takes over

D. Clinical/Miscellaneous:

1. Undrained abscess - antibiotics can't penetrate
2. Foreign body (prosthetic valve, catheter) - must remove
3. Wrong diagnosis - viral infection treated with antibiotics
4. Drug fever - mistaken for treatment failure

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12. LEPROSY (Anti-Leprosy Drugs)

Causative organism: Mycobacterium leprae (cannot be cultured in vitro)

Types relevant to treatment:

• Paucibacillary (PB) - TT, BT leprosy (few bacilli, <5 lesions)
• Multibacillary (MB) - BB, BL, LL leprosy (many bacilli, >5 lesions)

WHO Multidrug Therapy (MDT) - Mnemonic: "DRC"

Regimens:

• Paucibacillary (PB): Rifampicin (monthly) + Dapsone (daily) - 6 months
• Multibacillary (MB): Rifampicin (monthly) + Dapsone (daily) + Clofazimine (daily + monthly) - 12 months

Key Points for Exam:

• Dapsone side effects: Hemolytic anemia (dose-dependent), methemoglobinemia, peripheral neuropathy, hypersensitivity (Dapsone syndrome)
• Clofazimine: red-brown skin/urine discoloration (patient must be warned), anti-inflammatory (useful in erythema nodosum leprosum - ENL reactions)
• Rifampicin: once monthly supervised dose (600mg) in leprosy (unlike TB where it's daily)
• Type 1 reaction (Reversal reaction): Treat with steroids
• Type 2 reaction (ENL): Treat with Thalidomide (males/post-menopausal women) or Clofazimine or Steroids

Resistance in Leprosy:

• Dapsone resistance is common (monotherapy should NEVER be given) - reason for MDT

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QUICK REVISION TABLE

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Exam Tips:

• Always mention mechanism first in any question
• For side effects, memorize 2-3 unique/characteristic ones per drug
• Drug resistance mechanisms are frequently asked in short notes
• For TB and Leprosy, the regimens with duration are high-yield
• PEP - "72 hours" and "28 days" are the two most important numbers
• Cotrimoxazole and Sulfonamides share mechanism but learn their unique uses