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28 Cards in this Set
- Front
- Back
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Respiratory System- Tuberculosis Drugs by Bridges
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Respiratory System- Tuberculosis Drugs by Bridges
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What is the rule for treatment of active TB?
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COMBINATION THERAPY
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First line vs second line... what's the difference?
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based on efficacy and risk of drug toxicity.
2nd line drugs are used for TB strains resistant to 1st line. They tend to be more toxic and less efficacious. |
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What are the first line therapy drugs?
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Streptomycin
Rifampin Isoniazid Pyrazinamide Ethambutol RIPE: the primary ones used in combination -all are orally effective |
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Why do you use combined drug therapy for a prolonged period in effective treatment of TB?
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Synergy, reduce dosages, reduce toxicity of some drugs
targeting different part of the bugs' life cycle. (RNA polymerase, Folate synthesis) The resistant mutants are already existing in the patient.** |
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Why are mycobacteria tough to treat?
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intrinsically resistant to antibiotics and:
-slow growing -can be dormant -lipid rich cell wall -infection can reside within host cells |
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Which drug do you use for a latent TB infection?
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isonizid. it can be used alone. if it can't be used, it can be switch for rifampin.
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Describe Isonizid, MoA
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narrow spectrum of activity (only used against mycobacteria)
MoA: inhibits synthesis of mycolic acids, a major component of the cell wall. -bactericidal agent -no apparent cross-resistance to other first line drugs |
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Hepatic clearance of Isoniazid
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-slow/rapid inactivators (metabolizers)
-bimodal distrubution; genetic polymorphism |
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Drug interactions of isoniazid
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inhibits CYP 3A4, 2E1, 2D6, 2C19
-can inhibit metabolism of many drugs (esp with 3A4) |
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Adverse Effects of isoniazid
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Inhibits Neurons and Hepatocytes
-drug induced hepatitis (pot'l fatal) -distinct from typical ALT elevation -age most important risk factor* -peripheral neuropathy and CNS toxicity --causes vit. B6 deficiency |
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Rifampin for latent infections
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this is the back-up to latent infections, after isoniazid. use if that can't be tolerated.
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MoA of rifampin
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RNA polymerase inhibitor (inhibit RNA synthesis)
effective against many Gram positives but not effective against gram negatives |
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Rifampin and CYP450...
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potent cyp450 INDUCER
-increases the elimination of lots of drugs -immunocompromised/HIV pts are susceptible to TB infections |
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Side effects for rifampin
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-generally well tolerated, but most common side effects are rash, fever, NVD, abdo pain
-rare to get hepatitis -flu-like symptoms - red-orange color to body secretions, etc |
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What is Rifabutin?
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alternative to rifamycin, which is a big problem to HIV patients (since it'll wipe out HIV drugs).
Since rifampin decreases NNRTI and PI levels (which is what you need for HIV therapy), rifabutin is a less potent inducer of the CYPs, so you can use this drug on the HIV patients, and they can keep using their HIV drugs |
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Pyrazinamide MoA
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MoA unclear. But it needs to be converted to active form by mycobacterial enzyme
-works well when microbacteria is in an acidic environment |
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Out of all the drugs, which is the most hepatotoxic?
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this one. pyrazinamide. so when in combination, you're able to use a lower dose and not kill you.
-it can also give you hyperuriciemia. --inhibit uric acid excretion. --may cause acute gouty arthritis |
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Which are the bacteriocidal drugs?
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RIP.
Rifampin Isoniazid Pyrazinamide -all three are hepatotoxic and RIP the liver. -all three are 'cidal' agents |
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Ethambutol unique characteristic
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it's bacteriostatic. the other first line drugs are bacteriocidal.
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MoA of ethambutol
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inhibits arabinosyl transferases (part of cell wall biosynthesis)
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Ethambutol may not be as effective of a first line drug, but what's the big thing about it?
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HELPS DECREASE THE EMERGENCE OF RESISTANCE
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Unique side effects of ethambutol
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Optic Neuritis
-loss of visual acuity -impaired red-green vision decreases uric acid excretion -also like pyrazinamide |
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Streptomycin use
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reserved for more serious TB infections
-severe, possibly life-threatening eg meningitis, disseminated disease |
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MoA Strepomycin
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-protein synthesis inhibitor
-bactericidal -IV, given parenterally (all others are oral) -limited distribution --crosses BBB --penetrates cells poorly --acts mainly against extracellular bacilli |
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Adverse for Strepomycin
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Ototoxicity
-vertigo and hearing loss Nephrotoxicity Dose related toxicities |
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When can you stop taking Ethambutol?
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can be discontinued if your testing comes back and shows that there's no drug resistance.
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What do you do if you're resistant to isoniazid?
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give them the other three drugs for 6 months. that's the standard therapy.
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