Antimycobacterials Flashcards
What are the risk factors associated with TB?
- low socioeconomic status
- TB-endemic areas
- travel
- immunocompromised
What are common challenges for treating TB?
- Only active form is susceptible to drug therapy
- Slow growing, long drug therapy
- Harder to treat longer it’s been around
- limited compliance with long treatment
What are the most common first-line drugs for treating TB?
Isoniazid, Rifampin, Ethambutol, Pyrazinamide, and Steptomycin
How is isoniazid selective to TB?
Isoniazid is a prodrug and is activated by TB-produced catalase-peroxidase (KATG), which the active form targets enoyl-acyl carrier protein - preventing fatty acid elongation and formation of myocolic acid (InhA).
What are the different ways Isoniazid is used?
Used in combination with other drugs to treat an active infection.
Used independently to treat latent TB
How can polymorphisms effect metabolism of Isoniazid?
N-acetylation metabolism - slow metabolizers can have increased side effects and rapid metabolizers might need a higher dose.
What are common side effects of Isoniazid?
Neurotoxicity - peripheral neuritis
Hepatotoxicity - increased with age and other TB drugs
What antibiotic inhibits DNA-dependent RNA polymerase?
Rifampin - Bactericidal
What is a major problem with using Rifampin?
Potent inducer of cytochromes, causes significant drug interactions. Always used in combination with others in therapies. Hepatotoxicity worse in older population.
What drug can cause an orange color to urine, feces, tears, and sweat?
Rifampin
What antibiotic is TB-static and blocks synthesis of cell wall?
Ethambutol
What is the mechanism of Ethambutol?
Interferes with arabinosyl transferase blocking cell wall synthesis. Bacterial-static
What are the side effects of Ethambutol?
Optic neuritis - causing visual effects, unable to differentiate red from green
–Not Hepatotoxic–
What drug is only typically used in short term therapy?
Pyrazinamide
How does Pyrazinamide work?
Blocks synthesis of mycolic acid by inhibiting fatty acid synthase I. Bacteriacidal
What is a problem with using Pyrazinamide in combination with other drugs, especially Rifampin?
Hepatic Damage, increased severity when used with other drugs like Rifampin
What drug is typically reserved for serious TB infections only?
Streptomycin due to causing Ototoxicity and Nephrotoxicity
How does Streptomycin work against TB?
Binds to the 30S/50S complex, stops intiation and causes misreading
What are the typical guidelines for treating an active TB uncomplicated?
Isoniazid + Rifampin for ~6 months, sometimes with Pyrazinamide for 2 months
What would be the course if the TB was disseminated?
Isoniazid + Rifampin 9months-years, and Pyrazinamide and Ethambutol for first 2 months
What single agent drug would be used to prevent MAC infection in an AIDS patient?
Rifabutin - similar to Rifampin, except less hepatotoxicity and induction of cytochromes
What two drugs can be used to treat a MAC infection in an AIDS patient?
Clarithromycin in combination and Rifabutin in combination
Not used together
What drug has a similar mechanism as sulfa-drugs that is used to treat Leprosy?
Dapsone - inhibits folic acid synthesis
What drug can also prevent and treat Pneumocysitis jiroveci in AIDS patients?
Dapsone
What are common side effects of Dapsone?
Hemolytic Anemia and Methloglobinemia
What leprosy agent typically causes a build up of brown-red pigmentation?
Clofazimine
What drug is typically used with Dapsone to treat Laprosy?
Rifampin
