Antimycobacterials Flashcards
First line antimycobacterial drugs:
ethambutol, isoniazid, pyrazinamide, rifampin, rifabutin, refapentine
Mycobacteria morphology
rod-shaped bacteria with unusually waxy cell walls containing mycolic acid (fatty acids)
What do mycobacteria infections result in?
slow-growing, granulomatous lesions that cause tissue destruction and become resistant to antibiotics easily
T/F mycobacteria are resistant to most antibiotics
true
What are characteristics of mycobacteria?
grow slowly, can be dormant, cell wall impermeable to many drugs, intracellular pathogens, can develop resistance
What is the most widely encountered mycobacterial infection? (and leading cause of death from infection)
tuberculosis
What action of tuberculosis is responsible for pulmonary tissue distruction?
granulomatous lesions
What mycobacterium condition is treated in a similar way to tuberculousis?
leprosy
What organism causes tuberculosis and where is the most common site of infection?
Mycobacterium tuberculosis, lungs
How long does it take to treat tuberculosis?
months to years, partially because of delayed diagnosis
Why does TB become resistant quickly?
prior treatment and pt failure to adhere to protocol
What is characteristic of a latent TB infection?
no symptoms, noninfectious, positive TB skin test, should be treated
What is characteristic of an active TB infection?
patient is sick (chest pain, cough, weakness, fatigue, weight loss), can be spread, more aggressive treatment
How many people worldwide are infected with TB and how many die each year?
1/3 of the world’s population, 2 million die
What are strategies for addressing drug resistance of TB?
multi-drug therapy that is continued well beyond the disappearance of clinical disease
What is directly observed therapy?
patient reports to doctor’s office for medication, increases compliance and decreases mortality rates
Which agent is the most potent?
isoniazid
What is Isoniazid’s MOA?
bactericidal, inhibits mycolic acid synthesis in the cell wall (resistance develops quickly if used alone)
Describe the development of resistance to isoniazid
associated with several chromosomal mutations (cross resistance does not occur)
What is isoniazids pharmacokinetics?
readily absorbed orally but impaired with food, effective against intracellular bacteria, metabolized by P450 (liver), excreted by kidney
What are the adverse effects of isoniazid?
hepatitis/idiosyncratic hepatotoxicity, peripheral neuropathies, mental abnormalities, convulsion, optic neuritis, hypersensitivity
Why does isoniazid create hepatitis?
when broken down in the liver, the metabolite is toxic and incidence increases with age and those who drink alcohol daily
What peripheral neuropathies does isoniazid cause?
paresthesia (numbness) of hands and feet
What are the three rifamycins?
rifampin, rifabutin, rifapentine
Which drugs are considered the first line therapy for mycobacterium?
rifamycins
T/F rifamycins can be given alone
false, never given as a single agent
Do rifamycins have broader or narrower antimicrobial activity than isoniazid?
broader
What is the MOA of rifamycins?
interact with bacterial RNA polymerase to block transcription
What does rifampin treat?
gram -/+ bacteria, mycobacteria, leprosy, prophylactic meningitis
How is resistance to rifampin created?
mutation decreasing affinity of RNA polymerase for the drug or decreased permeability of the drug
How is rifampin excreted?
liver metabolism and excretion!!
What are drug considerations with rifampin?
may require dose adjustments, it is a potent inducer of CYP450 enzymes and can shorten the half-life of many drugs
Which drug creates orange-red secretions?
rifampin
What are the adverse effects of rifampin?
nausea, vomiting and rash
How is rifabutin different than rifampin?
less CYP450 induction which leads to fewer drug interactions
What is a unique side effect to rifabutin not in rifampin?
uveitis
Which rifamycin is preferred for HIV patients?
rifabutin
Which rifamycin has the longest half life?
rifapentine (weekly dosing after 2 months)
What is the MOA of pyrazinamide?
bactericidal to actively dividing organisms, lowers intracellular pH and inhibits growth
What are adverse effects of pyrazinamide?
liver dysfunction (when combined w/ isoniazid or rifampin) and hyperuricemia (precipitate gout)
What is the MOA of ethambutol?
interferes with cell wall synthesis probably by inhibition of mycolic acid synthesis
T/F resistance is not a problem with ethambutol when given with other drugs
true
What are the adverse effects of ethambutol?
unilateral optic neuritis with decreased vision and loss of R/G, reversed upon discontinuation
