Anti Malarials Flashcards
Quinolines and related cmpds ( 3)
Quinine
Chloroquine
Primaquine
Artemesins (2)
Artemether
ACT with lumefantrine
Adjunctive with quinolines
Doxycycline
Clindamycin
Atovaquone-proguanil
Artemesins work against
P. Falcifarum
Asexual blood stages of p. Vivax
Artemisinins’ anti malarial activity attributed to:
Endoperoxide moiety
Artemisinins are not useful as prophylaxis (or mono therapy) due to
Short t 1/2
ACT (artemisinin based combo therapy) increases ___ and decreases ___
Efficacy
Resistance
Eg of ACT
Artemether-lumefantrine
ACT has drug-drug interactions with
Antiretrovirals/ protease inhibitors
May need to increase ACT dose
Artesunate provided by CDC only for
Pts with severe malaria dz, high level of malaria parasites in blood, inability to take oral meds, lack of access to IV quinidine, quinidine failure or contraindications
Quinine indications
- Chloroquine-R and MDR p. Falciform asexual blood stages
- gametocyte- cidal against p. Vivas and p. Ovale
Quinine interferes with ____ digestion
Heme
Quinine resistance in SE Asia and SA due to
Pfmdr1 gene amplification
Quinine adult fatal oral dose
2-8mg
Quinine toxicities
Generally well-tolerated
-cinchonism, tinnitus, deafness, visual disturbance, HA, NVD, flushing
Quinidine SE w/ G6PD deficiency
Hemolysis
Quinidine CI and drug interactions
- hypersensitivity
- hemolysis
- tinnitus, optic neuritis
- caution w/ cardiac dysrythmias
- aluminum antacids delay GI abs
- increases warfarin and dig levels
- decrease dose for renal dz
Quinine adjunctive therapies
Doxy, tetracycline, Clindamycin inhibit protein translation (kill progeny)
Chloroquine can be given ____. IM/IV/SC can be given with caution!
Oral
Chloroquine resistance associated w/
Pfcrt mutation
Chloroquine adverse effects
CV, CNS, pruritis, hemolysis with G6PD deficiency
Primaquine indications
- Acts on primary and latent hepatic stages of plasmodia
- effective against relapse of p vivax and p ovale
Primaquine adverse effects
- hemolysis (MUST screen for g6pd deficiency)
- hypoTN with parenteral routes
- CI in pregnancy
- must r/o g6pd for breast feeding infants
Primaquine mechanism
Electrophilic intermediates/ redox rxn
Atovaquone active against
P falciform blood and LIVER stages
Atovaquone mechanism
Inhibits electron transport
Atovaquone has high cure rates when combined with
Proguanil
Malaria prophylaxis
Atovaquone plus proguanil
Activations adverse effects
Decreased levels with rifampin/ tetracycline
Proguanil mechanism
Inhibits dihydrofolate reductase
Drugs that can target liver stage
- Atovaquone plus proguanil
- primaquine
