ANTI TB anti - Tuberculosis drugs 2ppt.pdf

The presentation is of anti Tb drugs

1. ANTITUBERCULOSIS DRUGS
PHARMACOLOGY
BSCN-DE GROUP 4

2. TUBERCULOSIS
•Causative agent; Mycobacterium Tuberculosis
•Primarily affects the lungs but capable of involving any organ system
(extrapulmonary TB).
•The disease is airborne, transmitted through inhalation of droplets from
an infected person during coughing or sneezing.
•According to WHO data, about one-quarter of the global population is
infected latently.
•The highest burden is in low-and middle-income countries, particularly in
sub-Saharan Africa and Southeast Asia.
•TB treatment always uses combination therapy because:
1.M. tuberculosisrapidly develops resistance to single drugs.
2.Different drugs target various bacterial populations (actively dividing and
dormant bacilli).
3.Combination therapy ensures bactericidal, sterilizing, and resistance-
preventing effects

3. CLASSIFICATION OF ANTI-TB DRUGS
Category Examples Key Features
First-Line Drugs Isoniazid, Rifampicin, Pyrazinamide,
Ethambutol, Streptomycin
Most effective, less toxic; form the
standard short-course regimen.
Second-Line DrugsEthionamide, Cycloserine,
Capreomycin, Aminoglycosides
(Amikacin, Kanamycin),
Fluoroquinolones (Levofloxacin,
Moxifloxacin), PAS, Bedaquiline
Used when resistance develops or
first-line drugs are not tolerated. More
toxic and less effective.
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4. FIRST LINE DRUGS
1. Isoniazid (INH)
•Chemical Structure:Isonicotinicacid hydrazide (C₆H₇N₃O); a simple
hydrazide derivative of nicotinic acid.
Drugs in the Class:
•Isoniazid
•(Ethionamide is a structural analogue, but second-line)
Indication:
•Primary drug for Mycobacterium tuberculosisinfection.
•Used for both active TB (in combination therapy) and latent TB (as
monotherapy for 6–9 months).
•Mostly for intracellular bacillli
•. Little effect on non-tuberculosis mycobacteria (except M. kansasiiat high
levels).
Important Drug Interaction
•Inhibits metabolism of phenytoin→ may cause toxicity (nystagmus,
ataxia), especially in slow acetylators.
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5. INH MOA, Adverse Effects, Pharmacokinetics and
Nursing Considerations (NC)
MOA
•It is a Prodrug activated by KatGenzyme→ inhibits enzymes (InhA, KasA) needed to
synthesize mycolic acid→ weakens cell wall. Bactericidal to rapidly growing TB;
bacteriostatic to resting bacteria.
Phamacokinetics
•Well absorbed orally. Food and aluminum antacids reduce absorption. Distributes widely
(including CSF). Metabolized by N-acetylation→ rate varies (fast vs. slow acetylators).
Excreted in urine. Dose ↓ in liver disease.
Adverse Effects
•Peripheral neuritis(hands/feet tingling) → due to pyridoxine (Vitamin B6) deficiency
→ Prevent by giving pyridoxine 25–50 mg/day(NC)
•Hepatitis(risk ↑ with age, alcohol, or rifampin)
•CNS effects: mental changes, seizures (in predisposed), optic neuritis
•Hypersensitivity: fever, rash
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6. 2. RIFAMYCINS
•Chemical Structure(Rifampicin/Rifampin):A semisynthetic
derivative of rifamycin B; a macrocyclic antibiotic with formula
C₄₃H₅₈N₄O₁₂.
Drugs in the Class:
•Rifampicin/ Rifampin
•Rifabutin
•Rifapentine (second-line alternatives within same family)
Indication:
•Active TB (core first-line agent)
•Latent TB (alternative to INH)
•Also used for prophylaxis of Neisseria meningitidisand
Haemophilusinfluenzaetype b carriage.
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7. Indications
Rifampin (Rifampicin)
•First-linedrug for standard TB treatmentin most patients.
•Most widely used and well-studied.
Rifabutin
•Preferred in patients with HIV on antiretroviral therapy (ART).
•Less CYP450 enzyme induction → fewer drug interactions.
Rifapentine
•Used when once-weekly dosingis needed (e.g., latent TB regimens).
•Longer half-lifeimproves adherence.
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8. RifamycinsMOA, and Pharmacokinetics
MOA
•Binds β-subunit of bacterial RNA polymerase→ blocks mRNA synthesis→ bactericidal. Selective for bacteria (does not affect human RNA
polymerase)
Pharmacokinetics
•Good Oral Absorption:Rifamycinsare well absorbed when taken orally; food may delay or slightly reduce absorption.
•Wide Distribution:They distribute to most tissues and body fluids —including lungs, liver, and macrophages. Adequate CSF penetration,
especially when meninges are inflamed.
•Enterohepatic Circulation:Concentrated in the liver, excreted into bile, reabsorbed in the intestine —prolonging their presence in the body.
•Metabolism:Rifampin and rifapentine are hepatic enzyme inducers(CYP450), leading to reduced effectiveness of many other drugs(e.g.,
oral contraceptives, warfarin, antiretrovirals).
•Rifabutin:Similar pharmacokinetics, but is a weaker CYP450 inducer, making it safer to use in HIV/AIDS patientson antiretrovirals.
•Elimination:Primarily through bile and feces, with a smaller portion excreted in urine—this causes the orange-red body fluid discoloration.
•Half-Life Variation:
•Rifampin:Shorter half-life (may shorten further due to enzyme induction).
•Rifabutin:Longer half-life → allows less frequent dosing.
•Rifapentine:Longest half-life → once-weekly dosing in continuation phasetherapy.
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9. Side Effects & Adverse Effects of Rifamycins
(Rifampin, Rifabutin, Rifapentine)
•Hepatotoxicity:All rifamycinscan cause liver inflammation; risk increases with alcohol use and when
combined with isoniazid. Monitor liver function tests regularly.
•Gastrointestinal Upset:Nausea, vomiting, abdominal discomfort may occur, especially at the start of
therapy.
•Hypersensitivity Reactions:Fever, rash, and flu-like symptoms may develop, particularly with
intermittent dosing.
•Orange-Red Discoloration of Body Fluids:Tears, sweat, saliva, urine, and feces may become orange-
red. Contact lenses can be permanently stained.
•Drug Interactions:Rifamycinsinduce hepatic cytochrome P450 enzymes, leading to reduced
effectiveness of many drugs (e.g., oral contraceptives, warfarin, antiretrovirals).
•Rifabutin-Specific Effects:May cause uveitis, skin hyperpigmentation, and neutropenia—more likely in
patients on antiretroviral therapy.
•Rifapentine:Similar effects to rifampin but milder; still must be used in combination therapy to avoid
resistance.
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10. Nursing Considerations
Monitor liver function(risk of hepatotoxicity).
Warn patient: harmless orange-red discolorationof urine, sweat, saliva, and tears(may stain
contact lenses).
Rifampinis a strong enzyme inducer→ it reduces effectivenessof:
Oral contraceptives
Warfarin
Protease inhibitors & many antiretrovirals
Rifabutinhas fewer drug interactionsand is preferred in HIV patientson ART.
Emphasize adherenceto prevent resistance.
Give on an empty stomach(if tolerated).
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11. 3. Pyrazinamide (PZA)
•Chemical Structure:Pyrazine-2-carboxamide (C₅H₅N₃O).
Drugs in the Class:
•Pyrazinamide (no close analogues in clinical use).
Indication:
•Essential in the intensive phase of TB therapy(initial first 2months)
•Combined with Isoniazid+ Rifampin+ Ethmbutol
•Helps shorten duration of TB therapy
•Particularly active in acidic environments within macrophages where
dormant bacilli persist.
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12. Pyrazinamide MOA,Adverse Effects, and
Pharmacokinetics
MOA
•Converted to active metabolite (pyrazinoicacid)by pyrazinamidaseenzyme in mycobacteria. Exact mechanism not fully
understood, but:
•Inhibits bacterial survival in acidic environments(lysosomes & macrophages)
•Most activeagainst intracellular mycobacteria.
Pharmacokinetics
•Orally effectiveand well absorbed.
•Distributes to all tissues, including CSF.
•Extensively metabolizedin the liver.
Common Side Effects
•GI distress(nausea, vomiting)
•Mild arthralgia (joint pains)
Serious Adverse Effects
•Hepatotoxicity / liver dysfunction(risk ↑ when combined with isoniazid + rifampin)
•Hyperuricemia→ may trigger gout attacksdue to urate retention
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13. NursingConsiderations (NC)
•Monitor liver function tests (ALT/AST)regularly.
•Assess for signs of hepatitis: jaundice, dark urine, fatigue.
•Monitor serum uric acidlevels.
•Teach patient to report joint pain or swelling.
•Stress strict medication adherenceto prevent resistance.
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14. 4. Ethambutol (EMB)
•Chemical Structure:2,2'-(ethylenediimino)-di-1-butanol (C₁₀H₂₄N₂O₂).
Drugs in the Class:
•Ethambutol (unique drug).
Indication:
•Component of first-line TB regimen to prevent emergence of resistance.
•ALWAYS USE IN COMBINATION THERAPY e.gRIPE-Rifampin, Isoniazid,
Pyrazinamide, and Ethambutol
•Active against both pulmonary and extrapulmonary TB.
•Bacteriostatic against M.tuberculosisand M.Kansasii
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15. Ethambutol MOA, Pharmacokinetics, Adverse effects,
and NC
MOA:
•Inhibits arabinosyltransferase, disrupting arabinogalactansynthesis → weakens the
mycobacterial cell wall.
Pharmacokinetics;
•Well absorbed orally; reaches CNS adequately(useful in TB meningitis).Excreted
unchanged in urine → adjust dose in renal impairment.
Most Important Adverse Effect; Optic Neuritis which causes ↓ Visualacuity
•Red–green color blindness(classical board exam question)
•Symptoms usually reversibleafter stopping the drug → so vision must be monitored
periodically.
Other Side Effect
•Decreased urate excretion → may worsen gout
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16. SECOND LINE DRUGS
6. Ethionamide
•Chemical Structure:Thioamide analogue of isoniazid (C₈H₁₀N₂S).
Drugs in the Class:
•Ethionamide
•Prothionamide(related compound used in some regions)
Indication:
•Multidrug-resistant TB (MDR-TB) regimens.
•Occasionally used in leprosy treatment.
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17. Ethionamide
MOA:
disrupts mycolic acid synthesis, like INH butnot exacltysame as INH
Pharmacokinetics
•Distribution:Wide, including CSF.
Key Toxicities:
•Gastric irritation (very common)
•Hepatotoxicity
•Peripheral neuropathy
•Optic neuritis
NC: Management:Give Vitamin B6to reduce neuropathy.
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18. 7. Streptomycin
•Chemical Structure:Aminoglycoside antibiotic (C₂₁H₃₉N₇O₁₂).
Drugs in the Class:
•Streptomycin
•(Amikacin, Kanamycin, Capreomycin –second-line analogues)
Indication:
•Used as an alternative first-line agent for severe TB forms (meningitis, miliary TB)
when injectables are required.
•Active mainly against extracellular TB bacilli.
•Reserved due to toxicity and emerging resistance.
•Key Toxicities;
•Ototoxicity + Nephrotoxicity(monitor hearing & kidneys).
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19. 8. Cycloserine
•Chemical Structure:4-amino-3-isoxazolidinone (C₃H₆N₂O₂).
Drugs in the Class:
•Cycloserine(unique).
Indication:
•Second-line drug for MDR-TB.
•Used only when resistance or intolerance to first-line agents
occurs.
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20. Cycloserine
MOA:
•Inhibitsbacterial cell wall synthesis(interferes with D-alanineincorporation).
Pharmacokinetics:
•Distribution:Well distributed, includingCSF.
•Elimination:Renal →Accumulation in renal impairment.
Key Toxicities (CNS related):
•Seizures
•Confusion
•Peripheral neuropathy
NC: Management:Give Pyridoxine (Vitamin B6)to reduce neuropathy risk.
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21. 9. Capreomycin
•Chemical Structure:Cyclic peptide antibiotic (C₂₅H₄₄N₁₀O₈).
Drugs in the Class:
•Capreomycin
•Viomycin (related peptide antibiotic, rarely used).
Indication:
•Injectable second-line agent for MDR-TB resistant to
aminoglycosides.
•MOA:
•Inhibits protein synthesis.
•Key Toxicities:
•Nephrotoxicity(kidneys)
•Ototoxicity(hearing)
→ Requires close monitoring.
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22. 10. Fluoroquinolones (Levofloxacin, Moxifloxacin, Ofloxacin)
•Chemical Structure:
•Levofloxacin: C₁₈H₂₀FN₃O₄
•Moxifloxacin: C₂₁H₂₄FN₃O₄
Drugs in the Class:
•Fluoroquinolones: Levofloxacin, Moxifloxacin, Ofloxacin
Indication:
•Second-line agents for multi-drug resistant TB ( MDR-TB) and
extensively drug-resistant TB (XDR-TB).
•Highly active against replicating and dormant bacilli.
•Mechanism:Inhibit DNA gyrase / Topoisomerase.
•Key Toxicity:Tendon rupture, QT prolongation.
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23. Macrolides Used Against Tuberculosis (Brief Mention)
•Examples:
•Clarithromycin
•Azithromycin
•These agents show limited activity against M. tuberculosisbut are effective
against atypical mycobacteria such as:
•Mycobacterium aviumcomplex (MAC)
•Mycobacterium kansasii
•Mycobacterium abscessus
•In tuberculosis management, macrolides may be considered when:
•Treating MDR-TB (in combination with other drugs), or
•Managing co-infection with NTM in immunocompromised patients (e.g., those with
HIV/AIDS).
•HIV patients:Azithromycin preferred→ fewer drug-drug interactionswith
antiretrovirals.
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24. References
•Katzung BG et al. Basic and Clinical Pharmacology, 16th ed. McGraw-Hill, 2021.
•Karch AM. Focus on Nursing Pharmacology, 9th ed. Wolters Kluwer, 2022.
•Lilley LL, Collins SR, Snyder JS. Pharmacology and the Nursing Process, 10th ed. Elsevier,
2022.
•Brunton LL, Hilal-Dandan R, KnollmannBC. Goodman & Gilman’s The Pharmacological Basis
of Therapeutics, 13th ed. McGraw-Hill, 2018.
•Clark, M. A., Finkel, R., Rey, J. A., & Whalen, K. (2011). Lippincott’s illustrated reviews:
Pharmacology(5th ed.). Wolters Kluwer Health/Lippincott Williams & Wilkins.
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