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ANTITUBERCULOSIS DRUGS

First-Line Drugs (HRZE S)

Drug-Specific Points

• Mechanism: Inhibits mycolic acid biosynthesis → mycobacterial cell wall disruption
• Pharmacokinetics: Well absorbed; distributed to CSF, crosses placental barrier; metabolized by acetylation
• Uses: First-line TB; chemoprophylaxis
• Adverse effects: Hepatotoxicity (risk ↑ in chronic alcoholics, elderly, rapid acetylators); Peripheral neuritis (due to pyridoxine competition — give pyridoxine to prevent); fever, skin rashes, anaemia

• Mechanism: Binds bacterial DNA-dependent RNA polymerase → inhibits RNA synthesis
• Kills both intracellular and extracellular bacilli including spurters
• Food reduces absorption; metabolized in liver
• Uses: TB, Leprosy, Meningococcal prophylaxis, Brucellosis (with doxycycline), Staphylococcal infections (with β-lactams)
• Adverse effects: Hepatitis (main AE), Flu-like syndrome, GI disturbances, Skin rashes/flushing

• Active only in acidic pH → effective against intracellular bacilli
• Mechanism: Inhibits mycobacterial mycolic acid biosynthesis (different pathway from INH)
• Adverse effects: Dose-dependent hepatotoxicity (main AE), hyperuricemia, anorexia, nausea

• Bacteriostatic drug
• Used in combination to prevent emergence of resistance
• Main adverse effect: Optic neuritis (decreased visual acuity, colour vision defect — red-green)
• Crosses BBB in meningitis

• Not effective orally → must be given IM
• Active against extracellular bacilli in alkaline pH
• Adverse effects: Ototoxicity, nephrotoxicity, neuromuscular blockade

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TB Treatment (WHO/RNTCP 2016)

1. Make patient non-infectious as early as possible
2. Prevent drug-resistant bacilli development
3. Prevent relapse
4. Reduce total duration of therapy

• Monoresistance — resistant to only one first-line drug
• Polydrug resistance — resistant to >1 first-line drug, but NOT both INH and Rifampin
• MDR-TB — resistant to both INH and Rifampin ± other first-line drugs
• XDR-TB — MDR + resistant to a fluoroquinolone + a second-line injectable (amikacin/kanamycin/capreomycin)

• Intensive phase (6–9 months): Kanamycin + Levofloxacin + Ethionamide + Cycloserine + Pyrazinamide + Ethambutol + Pyridoxine 100 mg/day
• Continuation phase (18 months): Levofloxacin + Ethionamide + Ethambutol + Cycloserine + Pyridoxine

• INH 300 mg/day (10 mg/kg in children) for 6 months
• Indications: Newborns of mothers with active TB; children <6 years with positive tuberculin test; household contacts; HIV patients with positive tuberculin test

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ANTILEPROTIC DRUGS

• Oldest, cheapest, most widely used antileprotic
• Mechanism: Structurally similar to PABA → competitively inhibits folate synthetase → prevents THFA synthesis → leprostatic effect
• Pharmacokinetics: Oral; widely distributed; concentrated in infected skin, muscle, liver, kidney; metabolized by acetylation
• Adverse effects: Dose-related haemolytic anaemia (especially in G6PD deficiency); methaemoglobinaemia; anorexia, nausea, vomiting, peripheral neuropathy

Leprosy Treatment Schedules (WHO MDT)

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ANTIMALARIAL DRUGS

Classification by Stage of Action

1. No agent is effective against sporozoites
2. Most antimalarials act on asexual blood stages except primaquine
3. Only primaquine and tafenoquine are effective against hypnozoites (latent tissue forms)
4. All agents with "quine" (primaquine, chloroquine, quinine) are effective against gametocytes except mefloquine and tafenoquine

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• 4-aminoquinoline; drug of choice for acute malaria (P. vivax, P. ovale, P. malariae, chloroquine-sensitive P. falciparum)
• Mechanism: Basic drug → taken up by acidic food vacuoles → inhibits heme polymerase → toxic heme accumulates → parasite membrane lysis → death
• Resistance common with P. falciparum
• Safe in pregnancy
• Other uses: Amoebiasis, Rheumatoid arthritis, Discoid lupus erythematosus
• Adverse effects: Nausea, vomiting, headache, visual disturbances; prolonged use → irreversible retinopathy; parenteral → cardiac arrhythmias, cardiac arrest

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Malaria Treatment Regimens (Summary)

• Chloroquine 600 mg → 600 mg (day 2) → 300 mg (day 3)
• • Primaquine 15 mg/day × 14 days (for radical cure in P. vivax/P. ovale)

• Artesunate 100 mg BD × 3 days + Sulphadoxine/Pyrimethamine (single dose, day 1) — India standard
• OR Artemether + Lumefantrine × 3 days (north-eastern states)
• • Primaquine 0.75 mg/kg single dose on Day 2 (gametocidal)

• Artesunate IV/IM: 2.4 mg/kg at 0h, 12h, 24h → then daily until oral ACT tolerated

📝 PHARMACOLOGY EXAM NOTES

Antituberculosis | Antileprotic | Antimalarial Drugs

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PART 1: ANTITUBERCULOSIS DRUGS

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🔷 First-Line Drugs — Remember: "HRZES"

Hisoniazid · Rifampin · Pyrazinamide · Ethambutol · Streptomycin

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1️⃣ ISONIAZID (INH)

• Kills TB bacteria by stopping mycolic acid production (mycolic acid builds the bacterial cell wall)
• It's a prodrug → gets converted to active form inside the bacteria

• Absorbed easily from gut
• Goes everywhere — CSF, placenta, tubercular cavities
• Broken down by acetylation in liver → excreted in urine

• ✅ First-line TB treatment
• ✅ TB chemoprophylaxis (prevention)

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2️⃣ RIFAMPIN (Rifampicin)

• Blocks DNA → RNA step (inhibits RNA polymerase)
• Kills both inside-cell and outside-cell bacteria
• Broad spectrum — also works on meningitis, staph, brucella

• Take on empty stomach (food reduces absorption)
• Metabolized in liver
• ⚠️ Turns urine/sweat/tears orange-red (harmless but warn patient)

• ✅ TB (with INH and others)
• ✅ Leprosy
• ✅ Meningococcal prophylaxis
• ✅ Brucellosis (with doxycycline)
• ✅ Staph infections (with β-lactams)

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3️⃣ PYRAZINAMIDE (PZA)

• Works only in acidic pH (inside cells/caseous lesions)
• Has sterilizing activity — kills remaining hidden bacteria
• Inhibits mycolic acid (different pathway than INH)

• Main: Dose-dependent hepatotoxicity
• Others: Hyperuricemia (gout), anorexia, nausea, fever

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4️⃣ ETHAMBUTOL

• Bacteriostatic (slows growth, doesn't kill)
• Inhibits arabinosyl transferase → stops cell wall building
• Used in combo to prevent resistance

⚠️ Optic Neuritis — blurred vision + can't see red/green colours → Check eye regularly; stop drug if vision changes

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5️⃣ STREPTOMYCIN

• Aminoglycoside antibiotic
• Kills bacteria outside cells, in alkaline pH
• Cannot be given orally → must be injected (IM)

• Ototoxicity (hearing damage)
• Nephrotoxicity (kidney damage)
• Neuromuscular blockade

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🔶 TB TREATMENT REGIMENS (WHO/RNTCP 2016)

4 Goals of TB Treatment (MDT):

1. Make patient non-infectious ASAP
2. Prevent drug resistance
3. Prevent relapse
4. Shorten treatment duration

Treatment Chart:

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🔴 Drug Resistance Types — Easy to Remember:

MDR-TB Treatment:

• Intensive (6–9 months): Kanamycin + Levofloxacin + Ethionamide + Cycloserine + PZA + Ethambutol + Pyridoxine 100 mg
• Continuation (18 months): Levofloxacin + Ethionamide + Ethambutol + Cycloserine

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💉 CHEMOPROPHYLAXIS OF TB

• Drug: INH 300 mg/day for 6 months
• Given to:
  1. Newborns of mothers with active TB
  2. Children <6 years with positive tuberculin test
  3. Household contacts of TB patients
  4. HIV patients + positive tuberculin test

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PART 2: ANTILEPROTIC DRUGS

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Leprosy Basics:

• Caused by Mycobacterium leprae (acid-fast bacillus)
• Chronic infectious disease

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1️⃣ DAPSONE (Most Important!)

• Looks like PABA → blocks folate synthetase → bacteria can't make folic acid → dies
• Same mechanism as sulphonamides

• Given orally; absorbed well
• Goes to infected skin, muscle, liver, kidney
• Metabolized by acetylation

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2️⃣ OTHER DRUGS:

• Clofazimine — Phenazine derivative; also anti-inflammatory
• Rifampin — Used in both TB and leprosy
• Ofloxacin, Minocycline, Clarithromycin — Alternative drugs

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💊 LEPROSY TREATMENT SCHEDULES (WHO MDT)

All drugs are given orally

💡 MBL = More Bacilli → More drugs, More months 💡 PBL = Pauci Bacilli → Less drugs, Less months

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PART 3: ANTIMALARIAL DRUGS

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Malaria Basics:

• Caused by Plasmodium species
• Transmitted by female Anopheles mosquito
• Species: P. vivax, P. ovale, P. malariae, P. falciparum (most dangerous), P. knowlesi

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🔶 Classification by Stage They Kill:

⭐ Must-Remember Points:

1. ❌ No drug works against sporozoites
2. Only Primaquine + Tafenoquine kill hypnozoites (prevent relapse in P. vivax/ovale)
3. Drugs with "quine" in name = effective against gametocytes
4. Most drugs work on asexual blood stages except primaquine

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1️⃣ CHLOROQUINE

• Drug of choice for uncomplicated malaria (P. vivax, P. ovale, P. malariae)
• Mechanism: Goes into parasite's acidic vacuole → blocks heme polymerase → toxic heme builds up → parasite dies
• ⚠️ Resistance common in P. falciparum

• Given orally; well absorbed
• Concentrates in liver, spleen, kidney, lungs, skin
• High affinity for melanin-containing tissues

• ✅ Malaria (drug of choice)
• ✅ Amoebiasis
• ✅ Rheumatoid arthritis
• ✅ Discoid lupus erythematosus
• ✅ Safe in pregnancy

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🔶 MALARIA TREATMENT REGIMENS (Quick Summary)

Uncomplicated Malaria:

• Chloroquine: 600 mg → 600 mg (day 2) → 300 mg (day 3)
• + Primaquine 15 mg × 14 days (for radical cure — kills liver hypnozoites)

• Option 1: Artesunate 100 mg BD × 3 days + Sulphadoxine/Pyrimethamine (day 1 single dose)
• Option 2: Artemether + Lumefantrine × 3 days (with fatty meal)
• + Primaquine 0.75 mg/kg single dose day 2 (kills gametocytes)

Severe / Cerebral Malaria:

• Artesunate IV/IM: 2.4 mg/kg at 0h → 12h → 24h → then once daily
• Switch to oral ACT once patient can swallow

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⚡ QUICK REVISION TABLE — All Drugs at a Glance

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💡 Exam Tips:

• INH peripheral neuritis → always give Pyridoxine (Vit B6)
• Ethambutol → always think eye/optic neuritis
• Streptomycin → never oral, always IM
• Chloroquine → safe in pregnancy, avoid in epilepsy
• Only Primaquine prevents relapse in P. vivax (kills hypnozoites)
• MDR-TB = resistant to H + R (most important drugs)