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🧫 ANTIMICROBIAL DRUGS - 6 Mark Exam Notes

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1. Classify Drugs Used in Malaria + MOA, Therapeutic Uses & Adverse Effects of Artemisinin

Classification of Antimalarial Drugs

Artemisinin - MOA

• Artemisinin contains an endoperoxide bridge that reacts with heme (iron) inside the parasite
• Produces free radicals that kill the parasite by damaging proteins and membranes
• Acts on all asexual stages including ring stage → fastest parasite clearance of all antimalarials

Therapeutic Uses

• First-line for uncomplicated falciparum malaria (always as combination therapy - ACT)
• IV Artesunate = drug of choice for severe/complicated malaria (superior to quinine)
• Active against gametocytes - reduces transmission
• Effective in multidrug-resistant P. falciparum

Adverse Effects

• Generally well-tolerated
• Neurotoxicity (in animal studies - high doses)
• Embryotoxic - avoid in 1st trimester of pregnancy
• GI disturbances - nausea, vomiting, diarrhea
• Mild QT prolongation (with lumefantrine combination)
• Short half-life → recrudescence if used as monotherapy

⚠️ Key Point: Monotherapy is STRONGLY DISCOURAGED. Always use ACT (Artemisinin Combination Therapy)

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2. Characteristic Features of Aminoglycosides

1. Mechanism of Action: Bind to 30S ribosomal subunit → inhibit protein synthesis → cause misreading of mRNA → bactericidal
2. Spectrum: Gram-negative aerobes (E. coli, Pseudomonas, Klebsiella); also Mycobacterium TB (Streptomycin)
3. Bactericidal - concentration-dependent killing
4. Poor oral absorption - must be given parenterally (IV/IM) for systemic infections
5. Not effective against anaerobes (require oxygen for uptake into cell)
6. Post-antibiotic effect (PAE) - continued killing even after drug levels fall below MIC
7. Synergism with beta-lactams (penicillin/ampicillin) - used together for serious infections
8. Toxicities (MAJOR):
   • Nephrotoxicity - tubular damage (monitor renal function)
   • Ototoxicity - cochlear (hearing loss) and vestibular (balance)
   • Neuromuscular blockade (rare - at high doses)
9. Resistance - by aminoglycoside-modifying enzymes (acetylases, adenylases)
10. Once daily dosing preferred (reduces nephrotoxicity, maintains efficacy due to PAE)

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3. Amphotericin B

MOA

• Binds to ergosterol in fungal cell membrane (not cholesterol in human cells - selective toxicity)
• Forms pores/ion channels in the membrane
• Causes leakage of K⁺, Mg²⁺, and cellular contents → cell death
• Two mechanisms: pore formation + oxidative damage

Spectrum

Uses

• Drug of choice for severe systemic fungal infections
• Cryptococcal meningitis (with flucytosine)
• Invasive aspergillosis
• Mucormycosis (drug of choice)
• Leishmaniasis (liposomal form)

Adverse Effects (Major - "Ampho-TERRIBLE")

Lipid Formulations

Resistance

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4. Albendazole vs Mebendazole

Memory tip: Albendazole = Acts systemically (Neurocysticercosis, Hydatid). Mebendazole = mainly gut.

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5. Anti-Tubercular Drugs

First-Line Drugs (RIPE)

Second-Line Drugs

Standard Regimen

• Intensive phase: RIPE x 2 months
• Continuation phase: RI x 4 months
• Total = 6 months (2HRZE/4HR)

Key Points

• INH is bactericidal in actively dividing organisms
• Pyrazinamide works in acidic pH (inside macrophages)
• Rifampicin is a potent enzyme inducer - many drug interactions
• Never give single drug (resistance develops rapidly)

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6. Classify Penicillin

Classification of Penicillins

• Penicillin G (Benzylpenicillin) - IV/IM
• Penicillin V (Phenoxymethylpenicillin) - Oral (acid stable)
• Spectrum: Narrow - Streptococci, Treponema, Clostridium

• Cloxacillin, Dicloxacillin, Flucloxacillin, Methicillin, Nafcillin
• Used for MSSA infections

• Ampicillin, Amoxicillin
• Gram +ve + some Gram -ve (H. influenzae, E. coli, H. pylori)

• Carboxypenicillins: Carbenicillin, Ticarcillin
• Ureidopenicillins: Piperacillin, Mezlocillin
• Extended Gram -ve coverage including Pseudomonas

• Amoxicillin + Clavulanate (Augmentin)
• Ampicillin + Sulbactam
• Piperacillin + Tazobactam (Pip-Tazo)

MOA of All Penicillins

• Inhibit transpeptidase (PBP - Penicillin Binding Proteins) → prevent peptidoglycan cross-linking → weak cell wall → bactericidal

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7. Acyclovir (Acyclovis)

MOA (3-Step Activation - Very Important!)

1. Viral thymidine kinase phosphorylates acyclovir → Acyclovir monophosphate
2. Cellular kinases → Acyclovir triphosphate (active form)
3. Acyclovir-TP inhibits viral DNA polymerase and causes chain termination

Key: Selective toxicity - only activated in virus-infected cells (human cells lack viral thymidine kinase)

Uses

• Herpes Simplex Virus (HSV-1, HSV-2): genital herpes, oral herpes, herpes encephalitis
• Varicella Zoster Virus (VZV): chickenpox, herpes zoster (shingles)
• Prophylaxis in immunocompromised patients (bone marrow transplant, HIV)

Adverse Effects

• Generally well tolerated
• Nephrotoxicity (crystalluria - ensure good hydration)
• Neurotoxicity (tremor, confusion - with high IV doses)
• Local phlebitis (IV route)

Resistance

• Mutations in viral thymidine kinase gene (most common)
• Use Foscarnet or Cidofovir for acyclovir-resistant HSV

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8. Treatment of Neurocysticercosis

Treatment

• Albendazole 400 mg BD x 8-30 days = PREFERRED (better CSF penetration - ~40% of serum levels)
• Praziquantel 50 mg/kg/day x 15 days (alternative)
• Albendazole + Praziquantel together for multiple cysts

• Dexamethasone or Prednisolone
• Given to reduce inflammation and cerebral edema that occurs as parasites die

• For seizures (carbamazepine, valproate)

• For hydrocephalus (VP shunt)
• For single accessible cyst causing mass effect

Key Points

• Number, location, and viability of cysts determines treatment
• Viable cysts: antiparasitic + steroids
• Calcified/dead cysts: only anti-epileptics (antiparasitic not needed)
• Intraventricular cysts: may need surgery + antiparasitic

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9. Azole Antifungal Drugs

Classification

• Imidazoles: Ketoconazole, Clotrimazole, Miconazole, Econazole (mostly topical)
• Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

MOA

• Inhibit fungal cytochrome P450 enzyme (14-alpha demethylase)
• Blocks conversion of lanosterol → ergosterol
• Ergosterol depletion → disrupts fungal cell membrane → fungistatic (mostly)

Key Individual Drugs

Adverse Effects

• Hepatotoxicity (all azoles - monitor LFTs)
• Drug interactions - Azoles inhibit CYP3A4 → increase levels of many drugs
• Teratogenic - avoid in pregnancy
• Ketoconazole: inhibits testosterone synthesis → gynecomastia

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10. Clarithromycin

MOA

• Binds to 50S ribosomal subunit (23S rRNA) → inhibits translocation → inhibits protein synthesis → bacteriostatic (bactericidal at high concentrations)

Spectrum (Gram +ve + atypicals)

• Streptococci, Staphylococci (not MRSA)
• Atypical organisms: Mycoplasma, Chlamydia, Legionella
• H. pylori (part of triple therapy)
• MAC (Mycobacterium avium complex) in HIV patients
• Respiratory pathogens: H. influenzae

Uses

• Community-acquired pneumonia (CAP)
• H. pylori eradication - PPI + Clarithromycin + Amoxicillin (Triple therapy)
• MAC prophylaxis and treatment in AIDS
• Skin and soft tissue infections
• ENT infections (otitis media, sinusitis)

Advantages over Erythromycin

• Better acid stability (oral bioavailability)
• Longer half-life (twice daily dosing)
• Better tolerability (fewer GI side effects)
• Active metabolite (14-OH clarithromycin) adds to activity

Adverse Effects

• GI upset (less than erythromycin)
• QT prolongation - avoid with other QT-prolonging drugs
• Hepatotoxicity (rare)
• Inhibits CYP3A4 - drug interactions (theophylline, warfarin, statins)
• Metallic taste

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11. Cephalosporins

Generation-wise Classification

Key Memory Points

• "Go higher generation → more Gram -ve, less Gram +ve"
• Ceftriaxone = most commonly used (meningitis, typhoid, gonorrhea)
• Cross-allergy with penicillin - ~1-2% (ask allergy history)
• Cephalosporins do NOT cover: MRSA (except 5th gen), Listeria, Enterococcus, atypicals

Adverse Effects

• Hypersensitivity reactions
• Diarrhea, nausea
• Hypoprothrombinemia (bleeding) - some 3rd gen
• Disulfiram-like reaction with alcohol (cefoperazone, cefamandole)

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12. Aminoglycosides (Detailed - Same group as Q2)

1. Nephrotoxicity
2. Ototoxicity (cochlear + vestibular)
3. Neuromuscular blockade

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13. Metronidazole

MOA

• Enters cell by passive diffusion
• In anaerobic organisms, the nitro group is reduced by ferredoxin-linked electron transport
• Produces cytotoxic free radicals → damage DNA → strand breaks → cell death
• Selective for anaerobes and protozoa (aerobic cells cannot reduce the drug)

Spectrum

• Anaerobic bacteria: Bacteroides fragilis, Clostridium difficile, Clostridium perfringens
• Protozoa: Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis

Uses (Easy Mnemonic: "Amoebs Get Tricky")

Adverse Effects

• Metallic taste (very common)
• GI: nausea, vomiting, anorexia
• Disulfiram-like reaction with alcohol (AVOID alcohol)
• Peripheral neuropathy (long-term use)
• CNS effects - headache, dizziness, rarely encephalopathy
• Teratogenic (avoid in 1st trimester)

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14. Chloroquine

MOA

• Malaria parasite digests hemoglobin → releases heme (ferriprotoporphyrin IX)
• Normally parasite polymerizes heme into non-toxic hemozoin
• Chloroquine concentrates in parasite's acidic food vacuole (lysosomotropic)
• Inhibits heme polymerase → toxic heme accumulates → kills parasite

Spectrum

• Active against blood schizonts of P. vivax, P. ovale, P. malariae
• P. falciparum - WIDELY RESISTANT (use ACT instead)
• Gametocidal for P. vivax/malariae (not P. falciparum)

Uses

• Malaria prophylaxis (where chloroquine-sensitive)
• Treatment of P. vivax, P. malariae, P. ovale (add Primaquine for radical cure/preventing relapse)
• Rheumatoid arthritis (anti-inflammatory)
• SLE (hydroxychloroquine preferred)
• Amebiasis (hepatic - last resort)

Adverse Effects

⚠️ Key: Baseline ophthalmologic exam needed for long-term use. Contraindicated in retinal disease, G6PD deficiency, and psoriasis.

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Quick Revision Memory Tricks

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