anti-malarials Flashcards
chloroquine
tx and prophylaxis
P. vivax and P. ovale - active against blood parasites - NOT liver stage
DOC for p.vivax and ovale
chloroquine
DOC in tx in non-falciparum and sensitive uncomplicated falciparum malaria
chloroquine
chloroquine MOA
concentrates in parasite food vaculoes
prevents biocrystallization of Hgb breakdown product heme to non-toxic hemozin = accum of heme results in lysis of parasite and RBC
chloroquine resistance
putative transporter: PfCRT
chloroquine AE
fatal = most common drug used for suicide
pruritus
hemolysis - G6PD
chloroquine contraindication
psoriasis, porphyria, retinal abnormalities
parenteral tx of severe falciparum
quinidine
oral tx of falciparum (alt in chloroquine resistant areas)
quinine
first line for severe falciparum
quinine/quinidine
quinine/quinidne use
good against BLOOd - not liver stages
depresses O2 uptake and carb metabolism
intercalates into DNA = disrupting replication/transcription
quinine/quinidine AE
cinchonism - tinnitus, HA, nausea
HS
hematological abnl: thrombocytopenia, agranulocytosis
hypoglycemia - stimulates insulin release
uterine contractions: still used in pregnant pt (benefits outweigh risks)
hypotension
QT prolongation
blackwater fever: likely HS rxn - hemolysis and hemolgobinuria
quinine/quinidine contraindications
visual/auditory problems cardiac don't use with mefloquine can inc levels of warfarin and digoxin renal insuff (dec dose)
Category C pregancy
mefloquine
works against chloroquine resistant strains
related to quinine
MOA: destroys asexual blood forms
only medication recommended for chemoprophylaxis in pregannt women in chloroquine resistant areas
mefloquine
mefloquine use
effective against most strains of p. falciparum and vivax
what combo is used in uncomplicated malaria in south east asia
mefloquine + artesunate
mefloquine AE
neuro and psych: ringing, anxiety, depression, hallcuination
weekly dosing: n/v/d, beahviro disturbances
higher dosing: leukocytosis, thrombocytopenia, aminotransferase, arrhythmias
mefloquine contraindications
hx of epilepsy, psych disorders, arrhythmia, cardiac conduction defects
DONT GIVE WITH quinine/quinidine, halofantrine
safe in young and pregant
DOC eradication of dormant liver forms in vivax and ovale
primaquine
Primaquine use
acute vivax and ovale and terminal prophylaxis of vivax and ovale
chemoprophylaxis against falciparum and vivax
primaquine MOA
not understood - maybe oxidants disrupting mitochondria binding to DNA
primaquine AE
rare - leukopenia, agranulocytosis, leukocytosis, cardiac arrhtymias
**hemolysis or methemoglbinemia - esp in G6PD pt’s
what to test for before administering primaquine
G6PD - if deficient, must deal with dormant stages, cannot take at all
primaquine contraindications
DO NOT USE DURING PREGNANCY - until fetus is born and found if deficient
malarone
(combo of atovaquone + proguanil)
tx and prophylaxis of falciparum
NOT SAFE IN PREGANCY
malarone MOA
disrupt mitochondrial electron transport
pyrimethamine
folate synth inhibitor
proguanil
folate synth inhibitor
sulfadoxine
folate synth inhibitor
folate synth inhibitor application
chemoprophylaxis - only in combo of proguanil + chloroquine (not recommended)
intermittent therapy - high risk pt’s recieve intermittent therapy regardless of infection status
tx chloroquine resistant falciparum - NOT used in severe malaria
pyrimethamine + proguanil
act slowly against RBC form of malaria
inhibit plasmodial dihydrofolate reductase
proguanil active against which form/s
only active against some hepatic forms
sulfonamides active against which form
weakly against RBC schizonts
inhibit dihydropteroate synthase
folate synthesis inhibitors AE
well tolerated
proguanil - mouth ulcers
pyrimethamine-sulfadoxine = steven johnson
sulfadoxine - blood, GI,CNS,derm, renal toxic
proguanil and pyrimethamine-sulfadoxine = safe in pregancy
doxycycline
active against RBC schizonts NOT liver stage
complete tx for severe facliparum (alongside quinine) after initial tx
must be taken daily as chemoprophylaxis
doxycycline AE
photosensitive
discoloration/hypoplasia of teeth
not safe in pregnancy
fatal hepatoxicity (in pregnancy(
artemisin
artesunate
artemether
dihydroartemesinin (oral only)
coartem (artemether + lumefantrine)
artemesin use
IV severe falciparum malaria - don’t use alone to protect against resistance
only active in blood stage - not liver stage
artemesin MOA
binds iron, breaks down peroxide bridges = generates free radicals that damage parasites
very short t 1/2 - IV therapy + logner acting agent
artemisin AE
neurotoxicity, QT prolongation
safer in 2nd and 3rd trimersters
only use in 1st if severe
other antimalarials:
clindamycin - doxy alternative
halofantrine (RBC stages, teratogenic)
lumefantrine (RBC stages, minor QT prolongation)
DOC chemophrophylaxis in pregnant women
chloroquine
if chloroquine resistant: mefloquine
DOC SEVERE malaria tx in pregancy 1st trimester
quinidine or artesunate
DOC SEVERE malaria tx in pregnancy 2-3rd trimester
1st: artesunate
2nd: artemether
p. falciparum uncomplicated DOC
1) chloroquine/hydrochloroquine
chloroquine resistant:
1) atovoquone-proguanil/malarone
2) co-artem
3) quinine+doxycycline
4) mefloquine
P. malariae DOC
chloroquine/hydroxychloroquine
P. vivax/ovale DOC
1) chloroquine + primaquine
2) hydroxychloroquine + primaquine
P. vivax DOC in chloroquine resistant
1) quinine + doxycycline + primaquine
2) atovaquone - progaunil + primaquine
3) mefloquine + primaquine
uncomplicated malaria in pregnancy DOC
1)chloroquine/hydrochloroquine
- chloroquine resistant (falciparum)
1) mefloquine
2) quinine + clindamycin - chloroquine resistant (vivax)
Mefloquine
DOC severe malaria in all species
1) Quinidine + doxycycline or clindamycin
2) artesunate, followed by atovaquone-proguanil, clindamycin, or mefloquine
