TB and Malaria Flashcards
TB transmission
droplet nuclei, when a person with infectious TB sneezes, speaks, sings, or coughs
general facts about mycobacterium tuberculosis
acid fast bacteria, slow generation time which makes it difficult to treat, facultative intracellular parasite
property of cell wall that is unique to mycobacterium
mycolic acid
first line TB drugs
isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, rifabutin, rifapentine
4 drugs to treat active TB
RIPE
isoniazid, rifampin, pyrazinamide, ethambutol
recommended dosing for a new positive TB case
2 months: isoniazid, rifampin, pyrazinamide, ethambutol
4 months: isoniazid, rifampin
drugs to treat latent TB infection
isoniazid, rifampin, or isoniazid + rifapentine
isoniazid MOA
static
inhibits biosynthesis of mycolic acid
prophylaxis for TB
isoniazid
isoniazid inactivation
acetylation in the liver
isoniazid toxicities
hepatitis in fast acetylators
peripheral neuritis in slow acetylators
hemolysis
lupus like syndrome
rifampin MOA
inhibits DNA dependent RNA polymerase inhibiting transcription
rifampin spectrum
BROAD, effective against leprosy and also G+ and G- microbes
rifampin toxicities
hepatic enzyme induction, of CYP450s
not recommended for HIV patients
body secretions are orange
decreases effectiveness of birth control
ethambutol MOA
inhibits arabinosyl transferases involved in the synthesis of arabinogalactan
CNS penetration for ethambutol?
YES
if TB meningitis, this is a good drug to give
ethambutol toxicities
decreased of visual acuity and loss of green-red perception
pyrazinamide MOA
prodrug, mechanism unknown
active at acidic pH
CNS penetration for pyrazinamide?
YES
toxicities of pyrazinamide
hepatic dysfunction
pyrazinamide resistance
high, so it must be used in combination with isoniazid and rifampin
streptomycin MOA
binds on 30s ribosome
bacteriocidal
toxicities of streptomycin
ototoxic and nephrotoxic
rifamycin family MOA
inhibits DNA dependent RNA polymerase
2 drugs in rifamycin family
rifabutin and rifapentine
side effects of rifamycin drugs
body secretions are orange colored
inducer of P450, use rifabutin before rifapentine
DOC for latent TB
isoniazid + rifapentine
one of the DOC for active TB in HIV individuals
rifabutin (replaces rifampin)
reasons why second line TB drugs are second line
lower potency and/or greater toxicity
treatment for MAC
- clarithromycin or azithromycin
- ethambutol
- rifabutin, rifampin, or ciprofloxacin
treatment for mycobacterium leprae
1-5 patches: dapsone and rifampin for 6 months
> 5 patches: dapsone and rifampin for 6-12 months
dapsone MOA
PABA antagonist as well as interference with the nutrition of M. leprae
dapsone route of administration
oral
dapsone toxicity
nasal obstruction is most common
DOC for erythema nodosum leprosum
Thalidomide
toxicity of thalidomide
teratogenic
what are the 4 causative organisms to infect humans with malaria
P. falciparum, P. vivax, P. ovale, P. malariae
what two organisms remain dormant in the liver stages of malaria
p. vivax and p. ovale
malaria is most commonly caused by what species
p. falciparum
what are you treating for a clinical cure
patients symptoms
what are you treating for a radical cure
patients symptoms + dormant tissue forms
what form does a blood schizonticide work on
erythrocytic forms of the parasite
what stages does a tissue schizonticide work on
hepatic stages, think vivax and ovale
top 2 DOC for cholorquine resistant malaria
1: artesunate + atovoquone/proguanil
2: artemether-lumefantrine
DOC for malaria
Chloroquine
mechanism of resistance for cholorquine
transport pump removes drug from parasite
MOA of cholorquine
interferes with lysosomal degradation of Hgb leading to parasite toxicity
areas of the body where chloroquine accumulates
melanin rich tissues: skin, retina
toxicity of chloroquine
retinal and corneal toxicity (high, chronic doses)
hemolysis, QT prolongation, contraindicated in patients with psoriasis and porphyria
artemisinins: name the two and what its used for
artesunate and artemether
most rapid action of all current drugs against p. falciparum
must give with another antimalarial due to short 1/2 life
MOA for proguanil and pyrimethamine + sulfadoxine
inhibition of folate metabolism
sulfadoxine: inhibits incorporation PABA into folic acid
pyrimethamine and proguanil: inhibit DHF to THF
relationship of malarone (atovaquone + proguanil)
synergistic
MOA of malarone
atovaquone: inhibits mitochondrial ETC and ATP synthesis
proguanil: DHF reductase inhibitor
what drug should be combined with malarone
artesunate
what drug is lumefantrine combined with
artemether
toxicity of lumefantrine
headache and QT prolongation
when would you use quinine or quinidine
complicated, chloroquine-resistant plasmodia
combine with doxy, tetra, clinda
quinine/quinidine toxicity
cinchonism, antiarrhythmic agent, QT elongation, diarrhea, hemolysis in G6PD deficient patients
what would you use to treat complicated, chloroquine-resistant plasmodia in children or pregnant women?
quinine + clindamycin
mefloquine toxicity
depression of myocardium, can cause seizures and may aggravate latent psychoses, vivid dreams
SHOULD NOT BE USED IN PATIENTS WITH HX OF MENTAL ILLNESS OR EPILEPSY
what drug should be used for empirical treatment and preventative intermittent therapy for malaria in pregnant women
pyrimethamine + sulfadoxine+ artesunate
what two drugs are tissue schizonticides
primaquine and tafenoquine
toxicity of primaquine
contraindicated in patients with SLE or RA, hemolytic anemia (caution for those with G6PD deficiency, avoid in pregnant/breastfeeding women, children < 6 months)
tafenoquine, blood or tissue stage?
BOTH
contraindications of tafenoquine
patients with G6PD deficiency or unknown G6PD status
