Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
67 Cards in this Set
- Front
- Back
malaria afflicts __ people and causes more than __ deaths per year
|
500 million people
2 million deaths |
|
why has malarial incidence been on the rise since the 1960's
|
removal of DDT from world market
|
|
form of malaria that is highly fatal but not chronic
|
p. falciparum
|
|
form of malaria that is uncommonly fatal but has a chronic recurrent stage
|
p. vivax
|
|
describe 3 categorical uses of antimalarial drugs;
|
1. prevention of DISEASE (not infection)
2. treatment- reduce blood stage parasite numbers until the patient is well 3. eradication- after return from exposure (not for endemic populations) |
|
what type of prophylaxis (prevention) kills parasite at liver stage
|
causal
|
|
what type of of prophylaxis kills or suppresses parasites in the early erythroyctic stage
|
suppressive
|
|
3% p. falciparum parasitemia
organ failure HCT <20 |
complicated malaria- medical emergency
|
|
quinine
QUINIDINE MEFLOQUINE halofantrine MOA? |
aryl-amino-alcohols
rapidly kill blood stage p. falciparum |
|
DOC for acute severe disease- cardiotoxicity
|
quinidine
|
|
DOC for most p. falciparum regions- neuropsychiatric concerns
|
mefloquine
|
|
CHLOROQUINE
amodiaquine mepacrine pyronaridine MOA? |
4-aminoquinolines
kills blood stage parasites |
|
DOC for Rx and Px for non-p. falciparum malaria
|
chloroquine
|
|
primaquine
tafenoquine MOA? |
8-aminoquinolines
non-growing parasite stages- hypnozoites in liver terminal prophylaxis |
|
contraindcated in G6PD def and pregnancy
|
8-aminoquinolines
|
|
doxycycline
clindamycin floroquinolones MOA? |
antibiotics, (I should know that, right?)
blood stage RX slow acting but effective |
|
DOC for prophylaxis in mefloquine resistant p. falciparum areas
|
doxycycline
|
|
MALARONE
fansidar maloprim |
combination chemicals
|
|
NEW drug for uncomplicated MDR p. falciparum
concerns of development of proguanil resistance |
malarone (proquanil and atovaquone)
|
|
remote Rx in Africa
|
fansidar (sulfadoxine and pyrimethamine)
|
|
given to europeans in Africa
|
maloprim (dapsone and pyrimethamine)
|
|
artemisinin and derivatives
MOA? FDA approved? |
endoperoxides
quin hao plant rapid killing blood stage parasites not FDA approved |
|
the primary regimen used to tx uncomplicated falciparum malaria in the US
|
oral quinine w/ doxycycline
|
|
diastereomers isolated from the bark of cinchona spp tree
|
quinine and quinidine
|
|
what else is quinine often used for
|
tx of leg cramps
|
|
quinidine was originally used as
|
an antiarrhythmic drug
|
|
why is quinidine the only treatment for malaria requiring parenteral therapy
|
i.v. quinine is not available in the US
|
|
what else is needed when giving quinidine i.v.
|
ICU environment- electrocardiogram and cardiovascular parameters need to be continuously monitored
|
|
quinine and quinidine are both metabolized by...
quinidine is a potent inhibitor of... |
CYP450
CYP2D6 |
|
what does severe malaria do to the pharmacokinetics of cinchonal alkaloids
|
1. clearance and volume of distribution are decreased
2. both drugs bind a-1-acid glycoproteins that are greatly increased during infection -> reduces the free drug fraction -> decreased efficacy and toxicity |
|
tinnitus
blurred vision headache nausea and dysphoria from quinine and quinidine |
cinchonism
('si[ng]-k&-"ni-z&m) |
|
what does quinidine do to QTc
|
prolongation
|
|
in what patient population is hypoglycemia from stimulation of insulin secretion from quinine and quinidine more likely
|
pregnant women and severe malaria patients
|
|
MCC of drug induced ITP
|
quinine
|
|
massive hemolysis
hemoglobinemia AND hemoglobninuria |
blackwater fever
(from quinine and quinidine) |
|
treatment of non falciparum malaria and treatment of autoimmune diseases
|
chloroquine
|
|
chloroquine MOA
|
accumulates in acidic food vacuole of parasite -> becomes protonated and entrapped -> interferes w/ heme polymerase -> inhibits polymerization of toxic heme -> accumulates to levels that kill parasite
|
|
what is the chloroquine active metabolite
|
desethylchlorquine
|
|
fansidar MOA
|
pyrimethamine (a benzylpyrimadine)- inhibits dihydrofolate reductase
sulfadoxine (a sulfonamide)- inhibits conversion of PABA by dihydropteroate synthetase -> impacts THF synthesis |
|
what happens when fansidar is used widespread
|
resistance develops rapidly
|
|
why isn't fansidar a prophylactic drug
|
sulfonamide induced blood dyscrasias- hypersensitivity reax- hepatitis, vasculitis, exfoliative dermatitis (Steven's Johnson)
|
|
drug developed to replace chloroquine; widespread publicity for associated neuropsychiatric disorders
|
mefloquine
|
|
uses of mefloquine
|
1. first line for MDR malaria prophylaxis
2. second line for MDR uncomplicated malaria |
|
contraindicated in patients w/ hx of seizure disorders, or neuropsychiatric disturbances
sinus bradycardia QTc prolongation |
mefloquine
|
|
mefloquine resistance is widespread in ...
|
Thailand (mechanism is an efflux pump)
|
|
why isn't it recommend that halofantrine be given with food, even though absorption is significantly increased in the presence of dietary lipid
|
cardiotoxicity
prolongation of QTc and arrhythmia assoc death |
|
patients on halofantrine previously treated w/ ___, are more likely to have their QT interval prolonged
|
mefloquine
|
|
why can't doxycylcine and tetracycline be used as single agents for tx
|
slow acting!
|
|
when does doxycycline compliance become most difficult
|
when it must be given for 4 weeks after leaving the endemic area (not causally prophylactic- doesn't kill liver stage)
|
|
doxycycline MOA
|
inhibits protein synthesis by binding 30S and inhibits binding of aminoacyl-t-RNA
|
|
why are tetracylcines contraindicated in pregnant women and children
|
tooth and bone problems
|
|
an old drug used for the radical curative treatment of hypnozoites during or following treatment of relapsing malaria
|
primaquine
|
|
how is primaquine unique
|
it affects all species of plasmodia
is causally prophylactic (kills liver stages)- so doesn't need to be taken long after leaving endemic area) |
|
what special screening is needed before giving primaquine
|
G6PD screening
|
|
what dosing regimen of primaquine is needed for the p.vivax Chesson strain of the Southwest Pacific
|
twice the dose
|
|
weekly dosing regimens possible but only in phase III/IV trials
|
tafenoquine
|
|
proguanil (in atovaquone-proguanil = Malarone) must be metabolized to what active metabolite?
|
cycloguanil
|
|
is malarone causally prophylactic?
|
yes- both agents
|
|
tx and prevention of PCP and toxo
|
atovaquone alone
|
|
atovaquone MOA
|
inhibits mitochondrial electron transport at level of cytochrome bc1 complex
-> plasmodia have pyrimidine biosynthesis obligatorily coupled to electron transport, humans have a salvage pathway |
|
proguanil MOA
|
enhances the ability of atovaquone to collapse mito membrane potential
cycloguanil inhibits parasite dihydrofolate reductase |
|
what metabolizes proguanil to cycloguanil
|
CYP2C19
->10% of Caucasians are poor metabolizers |
|
resistance to atoquavone
|
point mutations in mito cytochrome B gene (Tyr268Asn mutation from Nigeria)
|
|
cycloguanil resistance
|
single point mutation in DHFR gene
|
|
artemether and artesunate
|
two artemisinin drugs used in Asia
|
|
most rapidly acting of all antimalarials
|
artemisinin derivatives
|
|
why is water solubility of artemisinin derivatives handy
|
can be administered by any route- even rectally
|