Anti-Malarials Flashcards
Ancient Chinese herbal remedy (sweet wormwood)
Artemisinins
Paired together because one has a short half life and one has a long half life. Both are blood schizontizides.
ACT with Lumefantrine (Coartem) Artemether+Lumefantrine.
Mainstay for chloroquine-R and MDR P. falciparum asexual blood stages; gametocyticidal against P.vivax and P.ovale
Quinine Sulfate
Highly effective against P. vivax, P.ovale, P. malaria and P. knowlesi and Chloroquine-S P. falciparum asexual blood stages, with some gametocytocidal activity.
Chloroquine Phosphate
Acts on primary and latent hepatic stages of plasmodia; effective against P. vivax and P. ovale.
Primaquine
Antibiotic that can be used in conjunction with anti-malarials.
Doxycycline
Antibiotic used in conjunction with anti-malarials to treat other protozoal infections like babesiosis, amebiasis and pneumocystitis jiroveci.
Clindamycin
Active against P. falciparum asexual blood stages and liver stages.
Atovaquone-Proguanil
Do anti-malarials work singly or do they have to be used in combination?
No single anti-malarial is effective against all liver and blood stages of the plasmodium life-cycle so you have to use a combination of drugs.
Active against P. falciparum and asexual blood stages of P. vivax as a gametocytocidal.
Artemisinins
Anti-malarial activity due to endoperoxide moiety
Artemisinins
Not useful for prophylaxis because of a short t 1/2 life. Results in increased failure as a monotherapy
Artemisinins
Artemisinin-based Combination Therapy (ACT) results in…
Increased efficacy and decreased resistance
Artemisinin’s MOA
Toxic adducts- Peroxide “bridge” potentially reduced by heme.
Substantial drug-drug interactions with anti-retrovirals/protease inhibitors (need to increase the anti-malarial dose)
ACT- Artemether-lumefantrine
Artemisin Adverse Effects
Generally well tolerated
Not recommended in 1st trimester of pregnancy or in children under 5kg.
Interferes with heme digestion
Quinine Sulfate
Resistance reported in SE Asia, South America from the Pfmdr1 gene amplification
Quinine Sulfate
Quinine Adverse Effects
Fatal oral dose (adults) 2-8 grams
Cinchonism: tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, flushing.
Hematologic abnormalities: hemolysis with G6PDH deficiency.
Quinine C/I
Caution in pts. with hypersensitivity
C/I in pts. with tinnitus/optic neuritis
Caution in pts. with cardiac dysrhythmias
Quinine DDI’s
Aluminum containing antacids delay GI absorption
Increased plasma warfarin and digoxin levels
Decrease dose in pts. with renal insufficiency
Interferes with Heme Digestion best to take Orally b/c parenteral routes can result in potentially lethal Cp
Chloroquine
Chloroquine MOA
Binds hemazoin in parasitized erythrocytes, causing cell lysis. pfcrt mutations associated with resistance (drug efflux also with CRT)
Chloroquine Adverse Effects
Narrow safety margin Acute toxicities in CV and CNS IV doses >5g usually fatal hemolysis with G6PDH deficiency Pruritis in persons of African descent
Hemolysis in G6PDH deficiency, screen before giving drug.
Don’t give IV b/c of risk of HoTN
C/I in pregnant women, screen babies for G6PDH deficiency before giving to a breast feeding mom.
Primaquine
Inhibits parasite mitochondrial ETC- inhibits CoQ turning on cytochrome b.
High cure rates when combined with proguanil.
Proguanil inhibits dihyrdofolate reductase. Synergistic with atovaquone.
Atovaquone-proguanil
Used for chemoprophylaxis/uncomplicated P. falciparum
Atovaquone-proguanil
