Exam 8: TB and Leprosy Flashcards
What are the 4 first line treatments for TB?
RIPE Rifampin Isoniazid Pyrazinamide Ethambutol
What are 3 drugs used to treat Leprosy?
Dapsone
Clofazimine
Rifampin
What drug is used to treat both TB and Leprosy?
Rifampin
What cells are primarily involved in immune defense against TB?
T Cells
In which cells does TB multiply in primary infection?
Alveolar Macrophages
What patient population is especially at risk of TB?
HIV/AIDS
Also foreign born patients
What are 3 different types of places TB organisms multiply?
- Cavitary Lesions- High O2, neutral pH (fast multiplication)
- Closed, Caseous Lesions- O2 low, neutral pH (replication is slow)
- Within Macrophages- Acidic (slow replication)
What 2 drugs are best at treating Actively multiplying TB (extracellular)?
Rifampin
Isoniazid
What drug is best at treating TB multiplying in macrophages (acidic environment)?
Pyrazinamide
What is the short course therapy for TB?
6 and 9 month regimens
Initial phase of Isoniazid, Rifampin, Pyrazinamide and Ethambutol for 2 months followed by a continuation phase of Rifampin and Isoniazid for 4 months.
What drugs are now preferred for preventative therapy/prophylaxis?
Rifampin and pyrazinamide
It used to be Isoniazid for 9 months, but this is changing due to resistance
What is the duration of preventative therapy?
2 months
What are the 3 types of Leprosy? What differentiates them?
Tuberculoid (most common. skin lesions with anesthesia) CMI High
Borderline
Lepromatous (CMI low)- Systemic. Characterized by anergy.
They differ due to differences in cell-mediated immunity
What animal can spread Leprosy?
Armadillos
What Leprosy drug has to be taken a long time? Shorter?
Dapsone (3 years)
Rifampin is only for 6 months
Clofazimine is like Dapsone (3 years)
Isoniazid (INH) Mechanism
Modified Vit B3 analogue
Inhibits synthesis of mycolic acid (cell wall component unique to mycobacteria)
Bacteriostatic for resting bacilli, but bactericidal if they are rapidly dividing ***
What is an important consideration with Isoniazid?
Genetic variation in acetylation speed between people is important considering INH toxicity
What are 2 main adverse effects of INH?
- Peripheral neuropathy
- Hepatitis
Slow acetlyators are most at risk
How do you treat peripheral neuropathy caused by INH?
Pyridoxine
What is the mechanism of Rifampin?
Inhibits DNa dependent RNA polymerase by binding to the Beta subunit (inhibits RNA synthesis)
What is the most common side effect of Rifampin? Others?
GI disturbances
Hepatitis
Orange color of urine, feces, sweat, tears, saliva.
Induces P450 enzymes
What is the mechanism of Ethambutol?
Inhibits incorporation of mycolic acid into the cell wall
What are adverse effects of Ethambutol?
Visual changes that are reversible
When is Pyrazinamide effective?
When the pH is slightly acidic.
What are adverse effects of Pyrazinamide?
Hepatotoxicity
non gouty polyarthralgia due to Hyperuricemia!
What is the mechanism of Clofazimine?
Binds to mycobacterial DNA and interferes with bacterial growth.
What is a pharmacokinetic property of Clofazimine?
Super long half life (70 days)
What are 2 adverse effects of Clofazimine?
Discoloration of the skin (red/brown)
GI disturbances
When is Clofazimine used?
Mostly for Lepromatous leprosy.
What is the mechanism of Dapsone?
Inhibits folic acid synthesis by inhibiting dihydropteroate synthetase (it is a sulfonamide)
Bacteriostatic
How is Dapsone metabolized?
Acetylated in the liver and excreted in the urine
What are adverse effects of Dapsone?
Hemolytic anemia
Methemoglobinemia
Sulfone syndrome- makes lepromatous leprosy worse sometimes
What is a good way to study this lecture?
Check out the charts at the bottom of his lecture notes.
