Respiratory Pharmacology
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I now have all the key information needed. Let me compile the comprehensive exam-focused overview.
Respiratory Pharmacology - Exam-Focused Overview
Source: Katzung's Basic & Clinical Pharmacology 16e, Murray & Nadel's Textbook of Respiratory Medicine, Goodman & Gilman's
1. BETA-2 ADRENOCEPTOR AGONISTS (Sympathomimetics)
Mechanism: Bind beta-2 receptors on airway smooth muscle → activate adenylyl cyclase → ↑ cAMP → bronchodilation + inhibit mast cell mediator release + reduce microvascular leakage + ↑ mucociliary transport.
Key rule: cAMP promotes bronchodilation. Beta-2 agonists increase cAMP synthesis; PDE inhibitors (theophylline) slow its degradation.
Short-Acting Beta-2 Agonists (SABAs)
| Drug | Key Points |
|---|---|
| Albuterol (salbutamol) | Most used SABA; first-line reliever; onset ~5 min; duration 4-6 hr |
| Terbutaline | Beta-2 selective; also used for premature labor tocolysis |
| Metaproterenol | Less beta-2 selective |
| Epinephrine, Isoproterenol | Non-selective; now largely replaced due to beta-1 effects (tachycardia, ↑ force of contraction) |
Adverse effects: Tachycardia (beta-1 spillover), skeletal muscle tremor, ↓ serum K+
Route: Inhalation preferred (maximal local effect, minimal systemic toxicity). Optimal particle size: 2-5 μm. Even so, 80-90% of inhaled dose deposits in mouth/pharynx.
Long-Acting Beta-2 Agonists (LABAs)
| Drug | Duration | Key Points |
|---|---|---|
| Salmeterol | 12 hr | Lipophilic; anchors to receptor; NOT for acute relief |
| Formoterol | 12 hr | Faster onset than salmeterol |
| Indacaterol, Vilanterol | 24 hr | Once-daily; COPD maintenance |
Exam alert: LABAs should NEVER be used as monotherapy in asthma - always combined with ICS. Use of ≥2 canisters of inhaled beta-agonist per month = marker for increased risk of asthma fatality.
2. MUSCARINIC ANTAGONISTS (Antimuscarinics / Anticholinergics)
Mechanism: Block parasympathetic (vagal) bronchoconstriction via M3 receptor antagonism on airway smooth muscle. Also block M1 (ganglionic) receptors.
Key receptor selectivity trick: Long-acting agents (tiotropium, etc.) bind M1/M2/M3 equally but dissociate fastest from M2 (presynaptic). This preserves M2-mediated inhibition of ACh release - a degree of functional selectivity.
Short-Acting (SAMAs)
| Drug | Notes |
|---|---|
| Ipratropium bromide | Quaternary ammonium - poor oral/CNS absorption; as effective as albuterol in partially reversible obstruction; 4-6 hr duration |
| Atropine | Prototype; limited by systemic absorption |
Long-Acting (LAMAs) - primarily for COPD
| Drug | Dose/Frequency | Notes |
|---|---|---|
| Tiotropium | 18 mcg once daily | 24-hr duration; reduces COPD exacerbation frequency; also approved for asthma add-on |
| Umeclidinium | 62.5 mcg once daily | 24-hr duration |
| Aclidinium | 400 mcg twice daily | 12-hr duration |
| Glycopyrrolate | Once daily |
Adverse effects: Dry mouth (most common), urinary retention (rare), concern for increased dementia risk with prolonged use. Do NOT combine short-acting + long-acting antimuscarinics.
3. INHALED CORTICOSTEROIDS (ICS)
Mechanism: Broad anti-inflammatory effects - inhibit production of inflammatory cytokines; reduce lymphocyte, eosinophil, and mast cell infiltration of airways; contract engorged bronchial mucosal vessels; potentiate beta-2 receptor effects. Do NOT directly relax airway smooth muscle.
Key concept: Reduce bronchial hyperreactivity and exacerbation frequency. Effect is preventive (controller), not a rescue medication.
| Drug | Notes |
|---|---|
| Beclomethasone | First ICS (developed 1970s); prototype |
| Fluticasone | High potency; widely used in combination inhalers |
| Budesonide | Commonly used; safe in pregnancy |
| Mometasone, Ciclesonide | High local potency |
Adverse effects (inhaled): Oropharyngeal candidiasis, dysphonia (use spacer/rinse mouth to reduce). Systemic effects (osteoporosis, adrenal suppression, cataracts) occur with high doses or prolonged use.
ICS in COPD: Benefit limited to patients with FEV1 ≤60% predicted. Early studies failed to show alteration of natural history. Improvement ~50-100 mL in FEV1.
4. METHYLXANTHINES
Mechanism: Nonselective phosphodiesterase (PDE) inhibitors → ↑ cAMP → modest bronchodilation. Also adenosine receptor antagonism (contributes to bronchodilation) + catecholamine release at toxic levels.
| Drug | Key Points |
|---|---|
| Theophylline | Most used; also improves inspiratory muscle function; anti-inflammatory effects |
| Aminophylline | IV form of theophylline |
Therapeutic range: 5-10 mcg/mL (formerly 15-20; narrowed due to toxicity). Narrow therapeutic index.
Adverse effects (dose-dependent): Insomnia, nausea/vomiting, cardiac arrhythmias, seizures. Warning: severe events (arrhythmias, seizures) may occur WITHOUT preceding nausea/insomnia warning.
Drug interactions: Blood levels affected by liver disease, CHF, age, many drugs (e.g., erythromycin, cimetidine increase levels; rifampin decreases levels).
Status: Not first-line - used as an alternative when LABAs/LAMAs are not tolerated or unaffordable.
5. LEUKOTRIENE PATHWAY INHIBITORS
Background: Leukotrienes (LTC4, LTD4, LTE4) are potent bronchoconstrictors derived from arachidonic acid via the 5-lipoxygenase pathway. Particularly important in aspirin-exacerbated respiratory disease (AERD).
Two subclasses:
a) Cysteinyl Leukotriene Receptor Antagonists (CysLT1 blockers):
| Drug | Dose | Notes |
|---|---|---|
| Montelukast | 10 mg once daily (adults); 4-5 mg children | No food interaction; once daily; no LFT monitoring needed; most prescribed |
| Zafirlukast | 20 mg twice daily | Taken on empty stomach; drug interactions (↑ warfarin levels) |
b) 5-Lipoxygenase Inhibitor:
| Drug | Notes |
|---|---|
| Zileuton | 1200 mg SR twice daily; slightly more effective than montelukast but requires periodic LFT monitoring |
Clinical uses:
- Mild persistent asthma (alternative or adjunct to ICS)
- Aspirin-exacerbated respiratory disease (AERD) - most effective class here
- Allergic rhinitis co-existing with asthma
Exam alert - FDA Boxed Warning (2020): Montelukast carries a black box warning for serious neuropsychiatric events: suicidality in adults/adolescents, nightmares and behavioral problems in children.
EGPA (Churg-Strauss): Early reports of eosinophilic granulomatosis with polyangiitis linked to zafirlukast/montelukast are now considered coincidental - the syndrome was unmasked by steroid dose reduction made possible by adding these agents.
6. TARGETED (BIOLOGIC / MONOCLONAL ANTIBODY) THERAPY
Targeting specific inflammatory mediators in severe, refractory asthma:
| Drug | Target | Key indication |
|---|---|---|
| Omalizumab | Anti-IgE | Allergic (atopic) asthma; reduces IgE-mediated mast cell activation |
| Mepolizumab, Reslizumab | Anti-IL-5 | Severe eosinophilic asthma (↓ eosinophil survival) |
| Benralizumab | Anti-IL-5Rα | Severe eosinophilic asthma; fast eosinophil depletion |
| Dupilumab | Anti-IL-4Rα (blocks IL-4 + IL-13 signaling) | Type 2 (T2-high) eosinophilic asthma; also atopic dermatitis |
| Tezepelumab | Anti-TSLP | Broad severe asthma (T2-high and T2-low) |
T2-high asthma = eosinophilic, IgE-mediated, responds to steroids and biologics. T2-low asthma = neutrophilic/paucigranulocytic, steroid-resistant, harder to treat - azithromycin (low-dose) shown to reduce exacerbation frequency.
7. PHOSPHODIESTERASE-4 (PDE-4) INHIBITORS
Mechanism: Block PDE-4 → ↑ cAMP → decrease airway inflammation. No direct bronchodilator activity.
| Drug | Indication | Notes |
|---|---|---|
| Roflumilast | COPD with chronic bronchitis + history of exacerbations | Reduces exacerbations; modest ↑ FEV1 (~50 mL); greatest benefit with eosinophilia or ≥2 exacerbations/year |
Adverse effects: Nausea, anorexia, abdominal pain, diarrhea, weight loss, sleep disturbance, headache. Monitor weight during treatment.
8. MAST CELL STABILIZERS
| Drug | Mechanism | Notes |
|---|---|---|
| Cromolyn sodium (sodium cromoglycate) | Inhibits mast cell degranulation; blocks Cl- channels | Inhaled; prophylactic only - NO bronchodilator effect; very safe; useful in exercise-induced and allergic asthma |
| Nedocromil | Similar to cromolyn | Less commonly used |
These are preventive agents only - useless during an acute attack.
9. MANAGEMENT FRAMEWORK
Asthma Stepwise Approach (exam summary):
| Severity | Treatment |
|---|---|
| Mild intermittent | SABA (albuterol) PRN only |
| Mild persistent | Low-dose ICS (controller) + SABA PRN |
| Moderate persistent | ICS + LABA (combination inhaler) |
| Severe persistent | High-dose ICS + LABA ± tiotropium ± biologic ± oral corticosteroids |
| Acute severe asthma | O2, frequent/continuous nebulized albuterol, IV/oral systemic corticosteroids (methylprednisolone 0.5 mg/kg every 6-12h) |
COPD Treatment Framework (GOLD guidelines):
- All patients: Smoking cessation (most important intervention), vaccination
- Symptomatic relief: SABA (albuterol) or SAMA (ipratropium) PRN
- Persistent symptoms: LABA or LAMA (or LABA+LAMA combination)
- Frequent exacerbators + FEV1 ≤60%: Add ICS to LABA/LAMA
- Chronic bronchitis + exacerbations: Roflumilast
- Theophylline: Alternative only if LABAs/LAMAs not tolerated
- Azithromycin (low-dose long-term): Reduces exacerbations, especially in non-eosinophilic COPD
10. HIGH-YIELD COMPARISON TABLE
| Drug Class | Onset | Duration | Asthma | COPD | Mechanism |
|---|---|---|---|---|---|
| SABA (albuterol) | Fast (min) | 4-6 hr | ✓ Rescue | ✓ Rescue | Beta-2 → ↑cAMP |
| LABA (salmeterol) | Slow | 12 hr | ✓ (with ICS) | ✓ | Beta-2 → ↑cAMP |
| SAMA (ipratropium) | ~15 min | 4-6 hr | Alternative | ✓ | M3 block |
| LAMA (tiotropium) | Slow | 24 hr | Add-on | ✓ First-line | M1/M3 block |
| ICS (fluticasone) | Days-weeks | Chronic | ✓ Controller | Selected | Anti-inflam |
| Theophylline | Hours | Variable | Alternative | Alternative | PDE inhibit |
| Montelukast | Hours | 24 hr | ✓ (mild) | Not recommended | CysLT1 block |
| Roflumilast | Days | Chronic | - | ✓ (selected) | PDE-4 inhibit |
| Omalizumab | Weeks | Chronic | ✓ (allergic) | - | Anti-IgE |
Key Exam Traps
- LABA monotherapy in asthma is contraindicated - always with ICS
- Tiotropium dissociates fastest from M2 (not M3) - preserves auto-inhibition of ACh release
- Theophylline toxic range - seizures/arrhythmias may occur WITHOUT nausea warning first
- Montelukast FDA black box (2020) - neuropsychiatric events including suicidality
- Cromolyn has NO bronchodilator effect - prophylactic only
- Roflumilast has NO direct bronchodilator effect - anti-inflammatory only
- AERD (aspirin-exacerbated respiratory disease) - best treated with leukotriene pathway inhibitors
- Optimal inhaled particle size: 2-5 μm; <1-2 μm particles are exhaled
Tuberculosis
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I now have comprehensive content from multiple textbooks. Let me compile the full exam-focused TB overview.
Tuberculosis (TB) - Exam-Focused Overview
Sources: Harrison's Principles of Internal Medicine 22e, Lippincott Illustrated Reviews Pharmacology, Katzung's Basic & Clinical Pharmacology 16e, Textbook of Family Medicine 9e
1. THE ORGANISM
- Mycobacterium tuberculosis - rod-shaped, non-spore-forming, obligate aerobe (0.5 x 3 μm)
- Acid-fast bacillus (AFB): stains poorly with Gram stain; once stained, resists decolorization by acid-alcohol due to high mycolic acid content in cell wall
- Cell wall: mycolic acids → arabinogalactan → peptidoglycan; creates very low permeability, reducing antibiotic effectiveness
- Divides slowly: every 18-24 hours in vitro
- Classically forms granulomatous lesions with caseous necrosis
2. EPIDEMIOLOGY
- Leading infectious cause of death worldwide (alongside HIV/AIDS)
- WHO 2023: 10.8 million new cases; 1.25 million deaths (including 160,000 in HIV co-infected)
- Top 8 countries (two-thirds of cases): India (26%), Indonesia (10%), China, Philippines, Pakistan, Nigeria, Bangladesh, DR Congo
- A quarter of the world's population is infected with M. tuberculosis (most with LTBI)
3. PATHOGENESIS & IMMUNOLOGY
Transmission: Airborne droplet nuclei from active pulmonary TB cases. Infection requires close, prolonged contact.
Primary infection sequence:
- Inhaled bacilli reach alveoli → phagocytosed by alveolar macrophages
- Bacilli resist killing → multiply within macrophages
- Macrophages release IL-12 → activates T lymphocytes and NK cells
- T cells produce IFN-γ → activates macrophages to kill bacilli (via reactive oxidants)
- Cell-mediated immunity forms granulomas (epithelioid macrophages + Langhans giant cells + lymphocytes)
- Central caseous necrosis develops within granuloma
Primary complex (Ghon complex): Subpleural parenchymal lesion + enlarged hilar/mediastinal lymph nodes.
Fate of primary infection:
- Most (>90%): contained → calcified → Latent TB Infection (LTBI)
- ~5-10%: progress to primary progressive TB (especially children, immunocompromised)
- ~5% reactivation later in life
Reactivation TB: Upper lobe apical/posterior segments (highest O2 tension favors mycobacterial growth). Produces cavitation, hemoptysis, systemic symptoms.
Risk factors for reactivation: HIV (greatest risk), TNF-α inhibitors (infliximab, adalimumab), diabetes, malnutrition, CKD, malignancy, silicosis, corticosteroids.
4. CLINICAL FEATURES
Pulmonary TB (most common)
| Feature | Details |
|---|---|
| Symptoms | Chronic productive cough (>3 weeks), fever, night sweats, weight loss ("consumption"), hemoptysis |
| CXR findings | Upper lobe infiltrates, cavitation, fibrosis, calcified Ghon complex, hilar adenopathy (in primary) |
| Pleural effusion | Lymphocyte-predominant exudate; low glucose; ADA elevated |
Extrapulmonary TB (hematogenous spread)
| Site | Notes |
|---|---|
| TB Meningitis | Most serious; lymphocytic CSF, ↑ protein, ↓ glucose; treat 12 months total; add glucocorticoids |
| Miliary TB | Hematogenous dissemination; "millet seed" pattern on CXR; all organs affected |
| Pott's Disease | Spinal TB; vertebral body destruction; cold abscess; paraplegia risk |
| Renal TB | Sterile pyuria; "putty kidney" calcification; hematuria |
| Adrenal TB | Bilateral adrenal destruction → Addison's disease |
| Pericarditis | Constrictive pericarditis (late) |
| Lymphadenitis | Cervical most common (scrofula); painless, rubbery nodes |
5. DIAGNOSIS
Tuberculin Skin Test (TST / Mantoux)
- Intradermal injection of 5 tuberculin units (PPD); read at 48-72 hours; measure induration (not erythema)
| Induration | Positive in... |
|---|---|
| ≥5 mm | HIV+, close TB contacts, organ transplant, CXR with fibrotic TB changes, immunosuppressed |
| ≥10 mm | Recent immigrants from high-prevalence countries, IV drug users, HCWs, prisoners, DM, silicosis, CKD, children <5 yr |
| ≥15 mm | All others with no risk factors |
Limitation: False negative with anergy (HIV, severe malnutrition, steroids, live vaccines). False positive with BCG vaccination and NTM infection.
IGRA (Interferon-Gamma Release Assays)
- QuantiFERON-TB Gold, T-SPOT.TB - detect IFN-γ release from sensitized T cells in response to TB-specific antigens (ESAT-6, CFP-10)
- Preferred over TST in BCG-vaccinated individuals
- Not affected by BCG; still affected by anergy
Microbiological Diagnosis (active disease)
| Test | Notes |
|---|---|
| AFB smear (Ziehl-Neelsen / auramine-rhodamine) | Fast; detects ≥10,000 bacilli/mL; low sensitivity (~50-80%) |
| Culture (gold standard) | Lowenstein-Jensen medium; takes 4-8 weeks; BACTEC system faster (2-3 weeks) |
| GeneXpert MTB/RIF (NAAT) | Rapid (2 hr); high sensitivity; also detects rifampin resistance (rpoB mutation) |
| Drug susceptibility testing (DST) | Required for all culture-positive cases |
6. TREATMENT: FIRST-LINE DRUGS (RIPE)
Mnemonic: RIPE or HRZE (H=Isoniazid, R=Rifampin, Z=Pyrazinamide, E=Ethambutol)
Standard 6-Month Regimen for Drug-Susceptible TB
| Phase | Drugs | Duration | Frequency |
|---|---|---|---|
| Intensive | HRZE (Isoniazid + Rifampin + Pyrazinamide + Ethambutol) | 2 months | Daily (preferred) |
| Continuation | HR (Isoniazid + Rifampin) | 4 months | Daily or 5 days/week |
Extension to 9 months (continuation phase to 7 months): if 2 months of pyrazinamide not completed, HIV+ not on ART, or prolonged culture conversion / cavitation on CXR.
TB Meningitis: Continuation phase extended to 10 months (total 12 months). Add dexamethasone.
Bone/Joint TB: Some authorities recommend 9 months total.
Drug-by-Drug Summary
A. Isoniazid (INH / H)
| Feature | Detail |
|---|---|
| Mechanism | Prodrug activated by mycobacterial KatG catalase-peroxidase → inhibits InhA (ketoenoyl-reductase) → blocks mycolic acid synthesis; also releases free radicals (nitric oxide) |
| Activity | Bactericidal against actively dividing cells; bacteriostatic against resting cells |
| Pharmacokinetics | Oral/IM; CSF penetration = serum; metabolized by NAT2 acetylation in liver |
| Acetylator status | Fast acetylators → lower serum levels; Slow acetylators → higher levels, more toxicity |
| Dose | 5 mg/kg/day (max 300 mg); 300 mg/day adults |
| Adverse effects | Hepatotoxicity (most serious; monitor LFTs); Peripheral neuropathy (B6/pyridoxine deficiency - give pyridoxine 25-50 mg/day prophylactically); CNS effects (seizures, psychosis in overdose) |
| Resistance mechanism | Mutations in katG (most common) or inhA promoter |
| Drug interactions | Inhibits CYP450; ↑ warfarin, carbamazepine, benzodiazepines, phenytoin levels |
B. Rifampin (Rifampicin / R)
| Feature | Detail |
|---|---|
| Mechanism | Inhibits DNA-dependent RNA polymerase (β-subunit, encoded by rpoB) → blocks mRNA synthesis |
| Activity | Bactericidal; kills actively dividing AND dormant "persister" organisms |
| Pharmacokinetics | Oral/IV; excellent CSF penetration; hepatic metabolism |
| Dose | 10 mg/kg/day (max 600 mg/day) |
| Adverse effects | Orange/red discoloration of urine, tears, sweat, saliva (warn patients!); hepatotoxicity; flu-like syndrome (with intermittent dosing); thrombocytopenia |
| Drug interactions | Potent CYP450 inducer → reduces levels of many drugs: OCP, warfarin, protease inhibitors, methadone, azole antifungals, corticosteroids |
| Resistance | Mutations in rpoB gene (detected by GeneXpert) |
| Related drugs | Rifabutin (preferred in HIV - less CYP induction); Rifapentine (long-acting, used in LTBI) |
C. Pyrazinamide (PZA / Z)
| Feature | Detail |
|---|---|
| Mechanism | Prodrug converted by pyrazinamidase (encoded by pncA) to pyrazinoic acid → disrupts membrane potential; active in acidic pH (within macrophage phagolysosomes) |
| Activity | Sterilizing activity against intracellular/dormant organisms; key drug enabling 6-month short-course therapy |
| Dose | 15-30 mg/kg/day (max 2 g/day) |
| Adverse effects | Hyperuricemia (inhibits uric acid secretion → can precipitate gout); hepatotoxicity; arthralgias; nausea |
| Only used in intensive phase (2 months) - not active at neutral pH of continuation phase |
D. Ethambutol (EMB / E)
| Feature | Detail |
|---|---|
| Mechanism | Inhibits arabinosyl transferase (EmbB) → blocks arabinogalactan synthesis → disrupts mycobacterial cell wall |
| Activity | Bacteriostatic; primarily included to prevent emergence of resistance |
| Dose | 15-25 mg/kg/day |
| Adverse effects | Optic neuritis (retrobulbar) → decreased visual acuity, red-green color blindness; dose-dependent and usually reversible if stopped promptly; check baseline vision before starting |
| Monitoring | Monthly visual acuity and color discrimination testing |
7. LATENT TB INFECTION (LTBI) TREATMENT
Goal: prevent progression to active disease. Test and treat: positive TST or IGRA + no active disease symptoms + no prior treatment.
| Regimen | Duration | Notes |
|---|---|---|
| Isoniazid (INH) daily | 9 months (preferred) | 270 minimum doses |
| Isoniazid + Rifapentine | 3 months once-weekly (12 doses) | With DOT; shorter, better adherence |
| Rifampin daily | 4 months | Good alternative; as effective as 9-month INH |
| Isoniazid + Rifampin | 3 months daily | Shorter option |
| Isoniazid daily | 6 months (alternative) | Less preferred than 9 months |
Pyridoxine (B6) 25-50 mg/day should be co-administered with isoniazid to prevent peripheral neuropathy.
8. DRUG-RESISTANT TB
Definitions
| Type | Definition |
|---|---|
| MDR-TB | Resistant to at least isoniazid AND rifampin |
| XDR-TB | MDR-TB + resistance to any fluoroquinolone + at least one additional Group A drug (e.g., bedaquiline, linezolid) |
| Pre-XDR-TB | MDR-TB + fluoroquinolone resistance |
MDR-TB Treatment
- Duration traditionally 18-24 months; newer regimens shortening to 6-9 months
- Core drugs: fluoroquinolone (levofloxacin or moxifloxacin) + any remaining active first-line drugs + second-line agents
- Second-line options: amikacin, cycloserine, ethionamide, p-aminosalicylic acid (PAS), clofazimine, linezolid
XDR-TB Treatment
- BPaL regimen: Bedaquiline + Pretomanid + Linezolid - now standard (may replace older second-line regimens)
- Bedaquiline: Inhibits mycobacterial ATP synthase; QTc prolongation (monitor ECG)
- Pretomanid: Nitroimidazole; kills both replicating and non-replicating TB
- Linezolid: Oxazolidinone; inhibits 50S ribosome; myelosuppression, peripheral neuropathy risk
- Clofazimine: Phenazine dye; generates cytotoxic oxygen radicals; skin discoloration (pink to brownish-black)
9. SPECIAL SITUATIONS
TB + HIV Co-Infection
- Start ART within 2 weeks of TB treatment if CD4 ≤50/μL
- Start ART within 8-12 weeks if CD4 ≥50/μL
- Exception: TB meningitis - delay ART initiation due to risk of immune reconstitution inflammatory syndrome (IRIS)
- Rifampin strongly induces CYP3A4 → ↓ protease inhibitor and NNRTI levels → use rifabutin instead (less potent CYP induction)
Pregnancy
- Safe: Isoniazid + Rifampin + Ethambutol (first-line)
- Avoid: Pyrazinamide (insufficient safety data), streptomycin (ototoxic to fetus)
- Give pyridoxine with INH
TB Meningitis
- HRZE x 2 months → HR x 10 months (total 12 months)
- Add dexamethasone (reduces mortality and neurological complications)
10. PREVENTION
| Strategy | Notes |
|---|---|
| BCG vaccine | Live attenuated M. bovis; given at birth in endemic countries; reduces severe childhood TB (miliary, meningitis) by ~80%; less effective against pulmonary TB in adults; causes false-positive TST |
| LTBI treatment | Most cost-effective prevention strategy |
| DOT (Directly Observed Therapy) | Reduces drug resistance and improves treatment completion |
| Infection control | N95 respirators for HCW; negative pressure isolation rooms; UV germicidal irradiation |
11. HIGH-YIELD EXAM TRAPS
| Drug | Classic Adverse Effect |
|---|---|
| Isoniazid | Peripheral neuropathy (prevent with pyridoxine); hepatotoxicity; lupus-like syndrome |
| Rifampin | Orange secretions; CYP inducer; hepatotoxicity; flu-like syndrome (intermittent) |
| Pyrazinamide | Hyperuricemia → gout; hepatotoxicity |
| Ethambutol | Optic neuritis → color blindness (red-green) |
| Streptomycin | Ototoxicity; nephrotoxicity; avoid in pregnancy |
| Bedaquiline | QTc prolongation |
| Linezolid | Myelosuppression, peripheral neuropathy |
| Clofazimine | Skin discoloration (pink/brown-black) |
Key mechanisms to know:
- INH → KatG activates → InhA inhibition → mycolic acid synthesis blocked
- Rifampin → RNA polymerase (β subunit / rpoB) inhibition
- PZA → active only in acidic pH (intracellular/phagolysosome) - explains why it is only used in first 2 months
- Ethambutol → arabinosyl transferase inhibition → cell wall arabinogalactan disrupted
Drug resistance keys:
- INH resistance: katG mutation (most common)
- Rifampin resistance: rpoB mutation (detected by GeneXpert)
- Both together = MDR-TB (always suspect with prior treatment failure or contact with MDR case)
DOT (Directly Observed Therapy) is the standard of care for all active TB to prevent resistance and ensure adherence.
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