Anti-Malarials Flashcards
what is the first-line anti-malarial?
chloroquine, but resistance is widespread
What is WHO’s first-line treatment for malaria if chlorquine resistant P. falciparum?
artemether-lumefantrine (Coartem)
target blood stages
which species of malaria cause a relapsing form (live in liver)
ovale - least common (Africa)
vivax - most common
P. vivax and falciparum make up what percentage of malaria infections?
95%
Where do the various agents act?
what is the only agent that acts at the hypnozoite stage?
primiquine
what are the only agents that acts at the hepatic schizont stages
primiquine
atovoquone-proguanil
(this occurs within 30 minutes of bite)
what agents only act at the blood schizont stage (not the gametocyte stage)
mefloquine
doxycycline
clindamycin
what agents act at the gametocyte stage (blood)
ACT
quinine
chloroquine
primaquine
atoquavone-proguanil
where do the artemesinins act?
blood stages of falciparum
some gametocyte of falciparum
asexual blood stages of vivax
what are the artemisinins?
artemether (PO/IM)
artesunate (rectal/IV)
what is the ADME of the artemesinins?
1-2 hr 1/2 life - not useful for prophylaxis
biliary excretion
what is the mechanim of action of the artemisinins?
peroxide bridge reduced by heme results in free radical production
What are the contraindications of the artemesinins?
1st trimester of pregnancy
children < 5kg
what are the S/E of the artemesinins?
decrease in RBC and neutrophils
transient heart block
*rare, dose, related; reversible
What is the ADME of Coartem?
Large Vd
t1/2= 4-5 days
absorption increased with high fat meal
drug-drug with antiretroviral/protease inhibitors
What are contraindications to ACT?
cardiac arrhythmias
cardiac disease
(kids and pregos)
what are the adverse effects of ACT?
Adults: GI distress, headache
Kids: fever, cough, vomiting, headache, anorexia
cardiac arrhythmias/neurologic symptoms with high doses
TAKE with fatty food or whole milk
what is the MOA of chloroquine?
inteferes with heme digestion
what is the ADME of chloroquine?
CYP3A4 metabolism
renal excretion
loading does required - high doses usually fatal
what’s the greatest thing about chloroquine?
It is safe in pregnancy!
What are the AEs of chloroquine?
GI distress
headache
visual disturbances
urticaria
rare hemolysis (increased with G6PD deficiency)
What are the contraindications of chlorquinolone?
epilepsy/myasthenia gravis
psoriasis/poryphia cutanea
advanced liver disease, blood disorders, severe GI or neurological disorders
can prolong QT
antacids delay absorption
decreases efficacy of yellow fever vaccine
quinine acts on what stages?
falciparum asexual blood stages
gemetocyticidal against vivax and ovale
What is the ADME of quinine?
oral, IM, IV (more toxicity)
readily absorbed, extensive tissue distribution
t1/2=11 hours
what are the AEs of quinine?
Cinchonism: tinnitus, hearing loss, visual disturbance, headache, nausea, vomiting, dizziness, postural hypotension
rash, angiodema, bronchospasm
blackwater fever: severe hemolysis (STOP)
IV - hypoglycemia, hypotension
fatal arrythmia and ITP at 2-8 g
what are the contraindications/cautions with quinine?
D/c if evidence of hemolysis
tinnitus/optic neuritis
caution: cardiac dysrhythmias
decrease dose in renal insufficiency
potentially safe in pregnancy (monitor glucose)
inhibits CYP3A4 (digoxin and warfarin)
what are doxycycline, clindamycin and tetracycline good for?
adjunct therapy with quinine/quinidine
they act slowly in killing blood schizonts by inihibiting protein translation in protozoa
when is primaquine active?
only agent that can eradicate liver stages of vivax and ovale
gametocytocial against falciparum
what must you do before giving primiquine?
screen for G6PD deficiency
What’s the MOA of primiquine?
interferes with mitochondrial ETC in parasite
what is the ADME of primiquine?
large Vd
t1/2=3-8 h
rapid hepatic metabolism and renal excretion
what are the contraindications of primiquine?
- pregnant women
- lupus and rheumatoid arth (if active)
- hemolytic anemia in G6PD deficiency (x-linked)
- 11% of AA males
- Sardinians, Sephardic Jews, Greeks, Iranians
what is the MOA of atovaquone?
inhibits mitochondrial ETC
what is atovoquone active against?
asexual blood stages and primary liver stages in falciparum (ONLY)
what is the ADME of atovoquone?
oral, lipophilic
slow absorption (increased with fatty meal)
t 1/2 2-3 days
no sig. metab, bilary excretion
what is the mechanism of resistance to atovoquone?
cytochrome b mutations inhibit drug binding
what are the AEs of atovoquone?
GI distress
headache
rash
risk can not be ruled out for pregos
rifampin/tetracycline reduce plasma levels
what is proguanil active against?
asexual blood and primary liver stages of falciparum and vivax
what is the MoA of proguanil?
inhbits dihydrofolate reductase
(enhances atovaquone effect)
what is the ADME of proguanil?
slow absorption
t1/2=18-20 hours
hepatic metabolism (CYP2C19)
renal excretion
is proguanil safe in pregnancy?
risk cannot be ruled out
where does mefloquine act?
against asexual blood stages
what is mefloquine used for?
prophylaxis and treatment of drug-resistant
falciparum
(best for prophylaxis)
MOA Unknown
what is the ADME of mefloquine?
rapidly absorbed (variable)
extensive Vd
t/12-13-24 days (extensive protein binding(
CYP3A4 metabolism mainly biliary excretion
what are the AE’s and contraindications of mefloquine?
GI distress and dizziness (short-term)
vivid dreams
black box: severe and permanent neuro and psych effects (10%)
2011: pregnant women, all trimesters CDC recommended
NO in seizures, depression bipolar
