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Flashcards in Antimalarials Deck (24):
1

Drugs that impair intra-parasitic heme polymerization

aka Hemazoin inhibitors (quinine derivatives)

 

Chloroquine

Mefloquine

Primaquine

Quinine/Quinidine

2

How do quinine drugs kill malaria?

By impairing their ability to carry out heme polymerization, parasites die from their own waste products

3

Is chloroquine safe in pregnancy?

Yes

4

How is P. falciparum resistant to chloroquine?

PfCRT

aka chloroquine pumps

 

Mefloquine was developed; however, P. falciparum soon developed PfMDR1 (Multi-Drug Resistance)

5

Taking into account P. falciparum's multi-drug resistance, where is chloroquine still considered useful?

Central America

Haiti

6

Mefloquine Side Effects

Neuropsychiatric

+

Vivid Dreams

7

Primaquine

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)

8

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

9

General side effects of quinolines

Cinchonism

Cardiotoxicity (esp., quinidine which caused long QT)

Hypoglycemia

10

Antifolate malarial drugs

Prymethamine

Proguanil

Sulfonamides

 

Inhibit nucleic acid synthesis (DHPS/DHFR)

11

What are antifolate drugs useful for in regards to malaria?

Nothing

 

They are not recommended because point mutations in DHPS/DHFR has lead to widespread resistance

12

Arteminisins

(wormwood derivatives)

Artesunate

Artemether/Lumefantrine (Coartem)

13

Why are artemisinins useful?

They have broader activity across the asexual life cycle of malaria

14

1st Line Drug for Severe Malaria

Artesunate (IV)

 

Note: Not FDA approved; however, available by request through the CDC

 

2nd line = Quinine (IV)

15

1st Line Drug for Uncomplicated P. falciparum in most of the world

Artemether/Lumefantrine

aka Coartem

 

Especially useful in Ghana

16

Atovaquone/proguanil (Malarone)

Doxycycline

Clindamycin

"other" antimicrobials

17

Atovaquone

Expensive for long term administration

Well-tolerated

Good for P. falciparum

 

Administer during primary liver/blood stage (attacks hypnozoites

18

Can doxycyline be given to pregnant women?

No

19

Can clindamycin be given to pregnant women?

Yes

20

What is doxycycline usually given in conjuction with?

Quinine

21

How can you spot an anopheles mosquitos?

(i.e., the one that transmit malaria)

They bite head first at a 45 degree angle

22

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

23

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

24

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?

  • Cut weeds in ponds: allows fish better access to malarial larvae 
  • Put oil in the water (kills larvae)
  • Paris green
  • Drain water
  • Mosquito nets