malaria pharmacology Flashcards
most common strains of malaria
P.falciparum ~75%
P.vivax/ovale
p.falciparum characteristics
- most common cause of mortality
- symptoms appear after 5-15 days after RBC lysis
p.vivax/ovale characteristics
- look very similar
- exoerythrocytic (liver) stage lasts for long
infection sequence of malaria
- female mosquito deposits spores
- spores collect in liver where they multiply for days to weeks
- spores enter RBCs, multiply
- RBCs lyse and spread more spores
symptoms of malaria
- anemia
- fever
- chills
- nausea
- flu-like symptoms
- hypoglycemia
- seizures
- multiple organ failure
stages of infection
- exoerythrocytic stage (liver)
- erythrocytic stage (RBC)
- latent (only P.vivax/ovale)
drug for exoerythrocytic stage
palurdrine (proguanil)
drug for latent exoerythrocytic
primaquine
rapid acting drugs for erythrocytic stage
chloroquine
quinine
mefloquine
artemisinin
slow acting drugs for erythrocytic stage
pyrimethamine
tetracyclines
sulfonamides
combo therapy drug
atovaquone/proguanil
proguanil MOA
inhibit plasmodial dihydrofolate reductase, inhibiting DNA synthesis
proguanil use
prophylaxis primarily, sometimes treatment
proguanil adverse effects
diarrhea
nausea
primaquine use
hepatic and latent p.vivax/ovule
primaquine adverse effects
mild GI
methemoglobinemia
primaquine contraindications
glucose-6-phosphate deficiency
chloroquine MoA
prevents parasite from inactivating heme
why isn’t chloroquine used much
resistance in p.falciparum is common enough
chloroquine adverse effects
- GI disturbances
- blurred vision
- possibly hypotension and cardiac arrest
chloroquine contraindications
psoriasis or porphyria, can cause flares
quinine MoA
interference with heme metabolism
quinine use
- treatment of choice for chloroquine resistant strains of p.falciparum
- NO Prophylaxis
quinine adverse effects
GI
vision
hypoglycemia
mefloquine MoA
unknown, maybe similar to chloroquine
mefloquine unique ADME
really long half life - 12-33 days
mefloquine use
prophylaxis and treatment
mefloquine adverse effects
GI
rarely neuropsychiatric effects
mefloquine contraindications
epileptic patients
psychiatric disorders
pregnant women
artemisinin MoA
produce reactive oxygen species that damage parasitic macromolecules
artemisinin use
initial treatment of p.falciparum
artemisinin adverse effects
very few reported
maybe allergic reaction
pyrimethamine MoA
inhibits plasmodial dihydrofolate reductase
pyrimethamine use
treatment only of chloroquine resistant strains of p.falciparum
or
in combo with sulfonamide
pyrimethamine adverse effects
GI
hypersensitivity reaction
pyrimethamine contraindications
megaloblastic anemia
tetracyclines use
- prophylaxis and acute treatment of p.falciparum
- often used in combo with quinine
most commonly used tetracyclines
tetracylcine
doxycycline
tetracyclines adverse effects
photosensitivity
GI
sulfonamides use
used in combo with pyrimethamine and quinine for resistant strains of p.falciparum
sulfonamides MoA
dihydrofolate reductase inhibitor
sulfonamides effectiveness
better at p.falciparum than vivax
atovaquone/proguanil MoA
inhibit mitochondrial function AND dihydrofolate reductase
atovaquone/proguanil counseling
eat with fatty meal once a day
atovaquone/proguanil use
prophylaxis and treatment of p.falciparum and p.vivax
atovaquone/proguanil adverse effects
uncommon
GI
atovaquone/proguanil contraindications
small children
pregnancy/lactation
malaria vaccine
RTS,S
how long after infection does malaria become symptomatic
1-3 weeks
phases of malaria infection
prodrome (HA, fatigue, ~10-21 days after infection) paroxysm (high fever, chills) cold phase hot phase (severe fever) sweating phase
fever is most common in which malaria strain
p.falciparum
important complication of p.falciparum
severe anemia
how to ensure positive diagnosis of malaria
thick and thin blood smears ever 12-24 hours for 3 days
what does thick smear detect
if parasite is present
what does thin smear detect
if plasmodium is present
giemsa stain
stain of the blood that makes thick and thin blood smears more reliable
treatment for uncomblicated malaraia
chloroquine
treatment for p.falciparum and vivax infection or severe illness
- admit to ICU
- quinidine for at least 24 hours and until PO can be started
- quinine + doxy
treatment for chloroquine-R p.falciparum, vivax, and ovale
mefloquine
treatment for p.falciparum if hx of seizure, cv issues or psychiatric issues
atovaquone/proguanil 2 BID for 3 days
monitoring for quinidine
EKG for long QT
hypoglycemia
monitoring for mefloquine
EKG
neurologic effects like hallucinations, psychosis
what to do with quinidine if QT interval is >0.6 sec
slow infusion
how often to check blood smears for parasitemia
every 12 hours until <1%
