Anti-Parasitics Flashcards
Are there vaccines for parasites?
No
What is constantly a problem in dealing with parasites?
Resistance
From what genus is malaria from?
Plasmodium
What are the 5 malaria parasites?
1) Falciparum
2) Vivax
3) Ovale
4) Malariae
5) Knowlesi
Which malaria is responsible for most deaths?
Falciparum
Which malaria is known to be “relapsing” due to hypozoites in the liver?
Vivax
What is a hypnozoite?
Dormant form of malaria
What is a second type of “relapsing” malaria found primarily in West Africa?
Ovale
Which malaria has a 24 hour life cycle and causes zoonotic infections?
Knowlesi
What is the first stage in the life cycle of falciparum?
Mosquito injects sporozoites (motile sporelike organism that is typically the infective agent introduced in the host).
After injection (stage 1) where do the sporozoites go and what do they become?
Liver and they form merozoites
What do merozoites do after stage 2?
Invade red blood cells
What happens after the merozoites infects the RBC?
It becomes a trophozoite (growing stage where it saps nutrients)
What happens to the trophozoites in the RBCs?
They multiply producing new merozoites.
What happens when the multiplied merozoites cause the RBC to rupture?
They infect other RBCs
What else can merozoites do besides infect new cells?
Become gametocytes
What do the gametocytes do?
Get picked up by new mosquito where they grow into sporozoites.
Classic symptoms of uncomplicated malaria?
Cold stage, hot stage, sweating stage, 48 hour periodicity for Falciparum and Vivax
More usual symptoms of uncomplicated malaria?
Fever and flu symptoms, anemia and jaundice
Signs of cerebral malaria?
Abnormal behavior, consciousness impairment, seizures, coma, and other neurologic complications
In severe malaria what will be seen in the urine?
Hemoglobinuria
When and how can malaria affect pregnancy?
Especially first pregnancy and causes low birth weight and miscarriage.
What are the 3 types of drug classification for malaria?
Tissue schizonticides, blood schizonticides, and gametocytocides.
What do tissue schizontices do?
Kill liver stage parasites
What do blood schizontices do?
Kill erythrocytic forms
What do gametocytocides do?
Kill sexual stages and block transmission.
Best option to deal with malaria?
Prevention
When should chemoprophylaxis be taken?
Before, during, and after travel
What should you consider before traveling?
Species the area, level/type of resistance, and time before travel
Prevention 1-2 days prior and 7 days after
Malarone: Atovaquine + Proguanil
Prevention 1-2 days prior and 4 weeks after
Doxycycline
Prevention 1-2 weeks prior and 4 weeks after
Chloroquine
Prevention more than 2 weeks before and continue 4 weeks after
Mefloquine
Prevention if >90 Vivax in area w/ 1-2 days prior and 7 days after
Primaquine
Main treatment for complicated malaria?
Quinidine gluconate plus doxycycline, tetracycline, or clindamycin.
Drawbacks of quinidine gluconate?
Hypotension, wide QRS/long QTc interval, and hypoglycemia
If quinidine gluconate doesn’t work what then?
Artsunate followed by malarian, doxycycline, or mefloquine
How is Artsunate administered?
IV only
3 characteristics about Artemisinin drug?
1) Potent and fast acting (10,000 fold reduction of parasites in 48 hours)
2) Low Toxicity
3) Resistance observed in SE Asia
How is Artemisinin activated?
Via heme iron
How does Artemisinin function?
Forms free radicals that target parasite proteins and lipids
How is Artemisinin shut down/resisted?
Mutations in Kelch 13 gene
What parasites does Artemisinin work on?
Blood schizonticide, not liver stages
How long is the half life of Artemisinin?
1-2 hours
How can Artemisinin be taken?
Only orally so low bioavailability
What do you do to correct for the low bioavailability of Artsemisinin?
Administer a semisynthetic via different route of transmission.
What pharmacologically association determines the effectiveness of Artemisinin?
Cmax
What is another way to counteract the short acting characteristic of Artemisinin?
Combine it with a drug with a longer half life.
When can artemisinin affect pregnancy?
First trimester
What are adverse side effects of Artemisinin?
Nausea, vomiting, diarrhea, and dizziness.
How does Chloroquine work?
Inhibits hemoglobin metabolism
How do parasites metabolize hemoglobin?
Ingestion of HG, breakdown into free heme, heme (toxic) to hemozoin (nontoxic)
What do 4-substituted quinolines interfere with?
Heme polymerization
Half life of Chloroquine?
3-5 days
How is Chlorquine taken?
Orally
Main side effect of Chloroquine?
Itching
When do you not use Chloroquine?
Psoriasis or prophyria, retina or visual field abnormalities, and myopathy
What interferes with absorption of Chloroquine?
Antidiarrheals and antiacids
Which malaria has the most resistance to Chloroquine?
Falciparum and Vivax
Where is the mutation that grants the resistance to Chlorquine?
PfCRT1 in the food vacuole
What is the mechanism for Quinine?
Similar to Chloroquinine with inhibition of heme polymerization
When do we use Quinine?
Chloroquinine resistant strains
What specific Quinine do we use for Chloroquinine resistant falciparum?
Quinine sulfate via oral
What specific Quinine do we use for severe falciparum malaria?
Quinidine gluconate via IV
Why do we not use quinine for prophylaxis?
Short half life and toxicity
What is cinchonism?
OD of Quinine. Tinting, headache, nausea, dizziness, flushing, and visual problems
How can Quinine affect pregnancy?
Stimulate uterine contractions
How can Quinine affect blood?
G6PD deficiency and blackwater fever (marked by hemoglobinuria)
What metabolizes Quinine?
CYP3A4
How can Quinine cause hypotension?
Too rapid infusion.
What does Mefloquine target?
Erythrocytic forms of falciparum and vivax
What is Mefloquine used for?
Prophylaxis and treatment