Antimalarials

Question 1

Drugs that impair intra-parasitic heme polymerization

Answer 1

aka Hemazoin inhibitors (quinine derivatives)

Chloroquine

Mefloquine

Primaquine

Quinine/Quinidine

Question 2

How do quinine drugs kill malaria?

Answer 2

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

Question 3

Is chloroquine safe in pregnancy?

Answer 3

Yes

Question 4

How is P. falciparum resistant to chloroquine?

Answer 4

PfCRT

aka chloroquine pumps

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

Question 5

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

Answer 5

Central America

Haiti

Question 6

Mefloquine Side Effects

Answer 6

Neuropsychiatric

+

Vivid Dreams

Question 7

Primaquine

Answer 7

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)

Question 8

Can primaquine be given to pregnant women?

Answer 8

No (do not know the G6PD status of the fetus)

Note: test all individuals for G6PD to avoid hemolytic reactions

Question 9

General side effects of quinolines

Answer 9

Cinchonism

Cardiotoxicity (esp., quinidine which caused long QT)

Hypoglycemia

Question 10

Antifolate malarial drugs

Answer 10

Prymethamine

Proguanil (used in prophylaxis)

Sulfonamides

Inhibit nucleic acid synthesis (DHPS/DHFR)

Question 11

Are antifolate drugs useful for treating malaria?

Answer 11

Not really

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

Question 12

Arteminisins

(wormwood derivatives)

Answer 12

Artesunate

Artemether/Lumefantrine (Coartem)

Question 13

Why are artemisinins useful?

Answer 13

They have broader activity across the asexual life cycle of malaria

Question 14

1st Line Drug for Severe Malaria

Answer 14

Artesunate (IV)

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

2nd line = Quinine (IV)

Question 15

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

Answer 15

Artemether/Lumefantrine

aka Coartem

Especially useful in Ghana

Question 16

Atovaquone/proguanil (Malarone)

Doxycycline

Clindamycin

Answer 16

“other” antimicrobials

Question 17

Atovaquone

Answer 17

Expensive for long term administration

Well-tolerated

Good for P. falciparum

Combined with Proguanil for prophylaxis (DOD 1st Line)

Administer during primary liver/blood stage (attacks hypnozoites)

Question 18

Can doxycyline be given to pregnant women?

Answer 18

No

Question 19

Can clindamycin be given to pregnant women?

Answer 19

Yes

Question 20

What is doxycycline usually given in conjuction with?

Answer 20

Quinine

Question 21

How can you spot an anopheles mosquitos?

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

Answer 21

They bite head first at a 45 degree angle

Question 22

How do Abx work against malaria?

Why are they not that useful?

Answer 22

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

Question 23

Drugs that can be used for prophylaxis

Answer 23

• 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 considers this 3rd Line

Question 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?

Answer 24

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