Antimycobacterial Drugs

What are mycobacteria?

Bacteria that:

• Grow slowly

• Have lipid-rich cell walls

• Can live inside cells

• Easily develop drug resistance

What diseases do mycobacteria cause?

• Tuberculosis (TB)

• Atypical infections (e.g., Mycobacterium avium)

• Leprosy

Why is TB treated with multiple drugs?

• Prevents drug resistance

• Increases effectiveness

• Single drug therapy is never used

What is the standard TB treatment approach?

-Combination therapy:

• Isoniazid + Rifampicin

• Add Pyrazinamide for first 2 months

-Duration:

• Usually 6–9 months

How does isoniazid work?

• Inhibits mycolic acid synthesis

• → weakens bacterial cell wall

Is isoniazid bacteriostatic or bactericidal?

• Low dose → bacteriostatic

• High dose → bactericidal

What is isoniazid used for?

• Active TB

• Latent TB

• TB prevention

Important side effects for isoniazid

• Peripheral neuropathy

• Hepatitis

• CNS toxicity

How do you prevent neuropathy when using isoniazid?

Give Vitamin B6 (pyridoxine)

Important drug interaction for isoniazid

Inhibits CYP450 enzymes

How does rifampicin work?

• Inhibits RNA polymerase

• → blocks RNA synthesis

Is rifampicin bactericidal?

Yes

What is rifampicin used for?

• TB

• Prophylaxis (e.g., meningitis contacts)

• Some serious infections

Key side effects for rifampicin

• Red-orange body fluids (urine, tears)

• Hepatitis

• Flu-like symptoms

Important drug interaction for rifampicin

• Induces CYP450

• → decreases effectiveness of many drugs

How does ethambutol work?

Inhibits cell wall synthesis

Is ethambutol bacteriostatic or bactericidal?

Bacteriostatic

Major side effect for ethambutol

• Optic neuritis

• Loss of vision

• Red-green color blindness

Who should avoid ethambutol?

Children (hard to monitor vision)

How does pyrazinamide work?

• Converted to active form (pyrazinoic acid)

• Mechanism not fully known

Is pyrazinamide bactericidal?

Yes

What is pyrazinamide especially good for?

• Intracellular bacteria

• Shortening TB therapy

Major side effects for pyrazinamide

• Hepatotoxicity

• Hyperuricemia → gout

• GI upset

What class is streptomycin?

Aminoglycoside

What is streptomycin used for?

• Severe TB (e.g., meningitis)

• Resistant cases

What does streptomycin mainly target?

Extracellular bacteria

When are second-line drugs used for TB?

• Drug resistance

• Severe side effects

• Treatment failure

How does ethionamide work?

Inhibits mycolic acid synthesis

Major side effects for ethionamide

• Severe GI irritation

• Neurologic symptoms

• Hepatotoxicity

How does cycloserine work?

Inhibits cell wall synthesis

Major side effects for cycloserine

• CNS toxicity (depression, psychosis)

• Peripheral neuropathy

Important precaution for cycloserine

• Give Vitamin B6

• Avoid in epilepsy

How does capreomycin work?

Protein synthesis inhibitor

Major side effects for capreomycin

• Nephrotoxicity

• Ototoxicity

What is amikacin?

Aminoglycoside (like streptomycin)

When is amikacin used?

Drug-resistant TB

How do Fluoroquinolones (Ciprofloxacin, Levofloxacin) work?

Inhibit DNA gyrase

When are Fluoroquinolones (Ciprofloxacin, Levofloxacin) used?

• Resistant TB

• Atypical mycobacteria

How do rifapentine and rifabutin work?

Same as rifampicin (RNA polymerase inhibition)

Key feature for rifapentine and rifabutin

• CYP450 inducers

• Cross-resistance with rifampicin

How does para-aminosalicylic acid (PAS) work?

Inhibits folic acid synthesis

Side effects for para-aminosalicylic acid (PAS)

• GI upset

• Crystalluria

• Hypersensitivity

How does dapsone work?

Inhibits folic acid synthesis

What is dapsone used for?

• Leprosy

• Pneumocystis pneumonia

Major side effects for dapsone

• Hemolytic anemia

• Methemoglobinemia

• Rash

How does clofazimine work?

• Possibly binds DNA

• Anti-inflammatory

What is clofazimine used for?

• Leprosy

• Drug-resistant TB

Major side effects for clofazimine

• Skin discoloration (red-brown/black)

• GI issues