Antimalarial Agents Flashcards
What are the 4 plasmodia species that are known to infect humans?
Falciparum
Vivax
Ovale
Malariae
Which two plasmodium species go dormant in the liver?
Vivax
Ovale
What are hypnozoites?
Dormant liver stage of vivax and ovale
Are falciparum and malariae ever dormant?
No
What is meant by secondary tissue forms of malaria?
It means the dormant liver phase
What does a clinical cure do?
Eradicates erythrocytic forms of the parasite
Secondary tissue forms in the liver not affected
What is a radical cure?
Eradicates all forms of the parasite, including secondary tissue forms
What do blood schizonticides do?
Give a “clinical cure” by acting on the erythrocytic form of the parasite
What do tissue schizonticides do?
Eliminate the hepatic stages of the parasite, and prevent relapses from vivax and ovale
Will tissue schizonticides suppress symptoms once erythrocytic stages have been established?
No
What is the most effective way to control malaria?
Don’t get bit by mosquitos
What 3 things do you need to take into consideration when choosing a treatment for your pt’s malaria?
- What species do they have?
- Do they have complicated or uncomplicated malaria: oral v parenteral
- Drug susceptibility of the infecting parasite (what area did they get it in, were they on chemoprophylaxis)
What are the blood schizonticides?
Chloroquine and hydroxychloroquine
Quinine sulfate and quinidune gluconate
Doxycycline and clindamycin
Artemisinin- artesunate OR artemether can be COMBINED with: Atovaquone-proguanil Lumefantrine Pyrimethamine-sulfadoxine Mefloquine
If there is no resistance, what is the DOC for a blood schizonticide?
Chloroquine
What is the main way malaria becomes resistant to chloroquine?
Transport pump
Can chloroquine be used prophylactically?
Yes, for organisms that are sensitive
What is the MOA of chloroquine?
It gets concentrated inside the parasite that is inside a RBC. Then it keeps the bug from degrading hemoglobin
How is chloroquine administered
Orally
In what tissues does chloroquine accumulate, and what are the side effects this causes?
Melanin-rich tissues: skin and retina
Causes skin discoloration and eye damage
How often do you need to administer chloroquine for prophylaxis?
Once a week (long duration of action)
What are the main toxicities of chloroquine?
QT prolongation
Eye and ear toxicity
Hemolysis-caution in G6PD patients
Exacerbates psoriasis and porphyria
Who is chloroquine contraindicated for?
Psoriasis
Porphyria
Which malaria drugs have the most rapid action?
The Artemisinins: artesunate and artemether
Why do you always combine the Art drugs with other antimalarials?
They have a very quick clearance, so any leftover malaria needs to be knocked out with another drug
What is the difference between artemisinin, artesunate, and artemether?
Artesunate and artemether and derivatives of artemisinin that have higher potency and bioavailability
When do we use ACT (artemisinin combination therapy)?
For chloroquine-resistant falciparum and vivax
Which ACT combos do we use first and are equally recommended?
Artesunate+ atovoqione-proguanil
Artemether+ lumefantrine
Which ACT combo is a drug of last resort?
Artesunate+ mefloquine
Which ART combo is reserved for pregnant women or IPT?
Artesunate+ sulfadoxine-pyrimethamine
Which drugs inhibit folate metabolism?
Proguanil
Pyrimethamine+sulfadoxine
How does malaria develop resistance to proguanil and pyrimethamine+sulfadoxine?
Mutations in DHFR (dihydrofolate reductase)
Remember, they inhibit folic acid metabolism
Why do we combine atovaquone and proguanil?
They have a synergistic effect!
Proguanil-targets folate via DHFR
Atovaquine- interferes with ATP
PLUS we then combine it with artesunate for rapid clearance and decrease in resistance
What do we have to give with proguanil when we give it to pregnant women?
Leucovorin, so that we can rescue the folate
What are the main side effects of lumefantrine+ artemether?
One of the main treatments for chloroquine resistant malaria
Headache in 56%
QT prolongation***
When would we use quinine and quinidine?
Complicated, chloroquine resistant malaria
VERY TOXIC
What do we have to combine quinine or quinidine gluconate with?
Doxycycline, tetracycline, or clindamycin
(Clindamycin is the only one safe for kids and pregant women)
By combining it with one of these, we reduce the length or treatment, and therefore, adverse side effects
What is the difference between quinine and quinidine?
Quinine-oral
Quinidine- oral AND IV- comatose pt gets IV quinidine
Quinine and quinidine are VERY TOXIC! What are the main toxicities?
Cinchonism (tinnitus, headache, dizziness, flushing, visual disturbances)
Antiarrythmic agent class 1A (quinidine only)
QT elongation (careful combining w mefloquine)
If a pregnant woman has chloroquine-resistant malaria, what do we have to avoid?
Quinine+ doxycycline/tetracycline
Mefloquine
Primaquine (tissue schizonticide)
(If giving proguanil, you must also give leucovorin to rescue folate)
What forms of malaria does mefloquine act on?
Erythrocytic
Is mefloquine a drug of absolute last resort?
Yes, it is toxic to another level
What are the main toxicities of mefloquine?
Depression of heart muscle (DON’T COMBINE with quinine)
Seizures
PSYCHOSIS**
Vivid dreams
Who should you never ever ever ever give mefloquine to?
history of mental illness
History of epilepsy
Pregnant
What drug is used for empiriacla treatment and preventative intermittent therapy in pregnant women?
Pyrimethamine+sulfadoxine
(Combined with artesunate)
Prevents spread from mom to baby
What forms of malaria is primaquine active against?
Tissue forms (it is a tissue schizonticide)
Can we use primaquine + a blood schizonticide as as radical cure/terminal prophylaxis?
Yes
What are the main toxicities of primaquine?
Hemolytic anemiaespecially if G6PD deficient**
Who should we NOT give primaquine to?
Pregnant women
Infants under 6 months
Breastfeeding women
G6PD deficient with extreme caution
Do pregnant moms get radical cures for malaria?
No, they can get clinical cure until the baby is delivered. We can’t give them primaquine due to the huge risk of fetal hemolytic anemia. (We don’t know if the baby is G6PD deficient)
What is the MOA of chloroquine?
It accumulates in the plasmodia and causes hemoglobin to accumulate, which is toxic
Are there a lot of side effects for atovaquone + proguanil?
No because it is a new drug
