Drugs that impair intra-parasitic heme polymerization
aka Hemazoin inhibitors (quinine derivatives)
How do quinine drugs kill malaria?
By impairing their ability to carry out heme polymerization, parasites die from their own waste products
Is chloroquine safe in pregnancy?
How is P. falciparum resistant to chloroquine?
aka chloroquine pumps
Mefloquine was developed; however, P. falciparum soon developed PfMDR1 (Multi-Drug Resistance)
Taking into account P. falciparum's multi-drug resistance, where is chloroquine still considered useful?
Mefloquine Side Effects
Target = Liver (good for P. vivax/ovale)
Useful after primary treatment to kill hypnozoites
NEEDS CYP2D6 to be converted to active form (people who do not have this enzyme, cannot make use of the drug)
Can primaquine be given to pregnant women?
No (do not know the G6PD status of the fetus)
Note: test all individuals for G6PD to avoid hemolytic reactions
General side effects of quinolines
Cardiotoxicity (esp., quinidine which caused long QT)
Antifolate malarial drugs
Inhibit nucleic acid synthesis (DHPS/DHFR)
What are antifolate drugs useful for in regards to malaria?
They are not recommended because point mutations in DHPS/DHFR has lead to widespread resistance
Why are artemisinins useful?
They have broader activity across the asexual life cycle of malaria
1st Line Drug for Severe Malaria
Note: Not FDA approved; however, available by request through the CDC
2nd line = Quinine (IV)
1st Line Drug for Uncomplicated P. falciparum in most of the world
Especially useful in Ghana
Expensive for long term administration
Good for P. falciparum
Administer during primary liver/blood stage (attacks hypnozoites
Can doxycyline be given to pregnant women?
Can clindamycin be given to pregnant women?
What is doxycycline usually given in conjuction with?
How can you spot an anopheles mosquitos?
(i.e., the one that transmit malaria)
They bite head first at a 45 degree angle
How do Abx work against malaria?
Why are they not that useful?
Target ribosomal fx within APICOPLAST ORGANELLE
Work too slowly for acutely ill
Use of these drugs for other reason may alter/delay the clinical presentation of malaria
Drugs that can be used of prophylaxis
- Chloroquine: 1 x wk (1-2 wks prior and 4 wks after)
Atovaquone/proguanil: 1 x daily (1-2 days prior and 1 wk after)
- DOD considers this First Line
- Doxycycline: 1 x daily (1-2 prior and 4 wks after)
- DOD conisders this 3rd Line
Youtube video at the end of the lecture (Walt Disney) had the 7 dwarves talk about ways to prevent malaria from spreading, what are they?