Antimalarials

Question 1

What do quinolines do?

Answer 1

Impairs intra-parasitic heme polymerization into hemozoin. Parasites digesting hemoglobin need to compartmentalize their waste products, if they can’t, then they die by their own waste.

Thus this works only on life cycle stages that consume hemoglobin

Question 2

Examples of quinolines

Answer 2

Quinine
Quinidine
Chloroquine
Hydroxychloroquine (Plaquinil) (although this is used more in rheumatology as an antimalarial)
Mefloquine
Primaquine
Lumefantrine

Question 3

What does chloroquine not work on?

Answer 3

P falciparum has a PfCRT ( P falciparum chloroquine resistance transporter) that pumps chloroquine out of the digestive vacuole

Question 4

For quinolines, which are prophylactic vs therapeutic?

Answer 4

Chloroquine and mefloquine are the only ones for prophylaxis.

Rest are therapeutic, although Primaquine can be used as a “radical cure”

Question 5

What quinines CAN be used to fight P Falciparum since we can’t use chloroquine?

Answer 5

Severe: Parenteral quinine/quinidine (IV not available in U.S.)

Uncomplicated: Oral quinine + doxy/clindamycin

Chloroquine can still be used in places that don’t have resistance (central America, Haiti, DR)

Question 6

What do we worry about with quinine and quinidine?

Answer 6

Quinine can cause cinchonism (tinnitus, headache, nausea, bitter taste)

Quinidine is an older generation antiarrythic. The dose we need for antimalarial status causes prolonged corrected QT intervals, so only use this in ICU settings where heart monitors are available.

Both can induce insulin secretion with a resultant hypoglycemia

Question 7

What do we tend to use chloroquine for?

Answer 7

P falciparum in Central America, Haiti, DR

P.vivax, Povale and P.malariae in most locations

Question 8

When do we give mefloquine and why is it so great for patients?

Answer 8

They can be dumb and forget their meds (3 week half life)

We use it for chloroquine resistant P. falciparum. Also a prophylactic

Question 9

What side effects and contraindications for mefloquine?

Answer 9

• Cardiotoxic if used with quinine/quinidine/halofantrine (kinda dumb since quinidine already is cardiotoxic alone)
• Neuropsychiatric side effects at treatment

Question 10

Who do we give mefloquine to?

Answer 10

Highly effective but it has a lot of side effect damage.

Only consider for pregnant women (category B), long term travelers who want to save money, and young children (adherence) and usually only as prophylaxis

Question 11

What is resistant to Mefloquine?

Answer 11

P. Falciparum (what a dick, seriously dude, stop it)

Multidrug resistance protein-1 (PfMDR1). Efflux pump for mefloquine, quinine, quinidine. And to boot, this has polymorphisms, so we get varied phenotypes. Hooray.

Question 12

What do we give primaquine for?

Answer 12

Prevention of relapses “only for persons who have had prolonged exposure in malaria-endemic areas (missionaries, Peace Corps volunteers, etc.) - Force Health Protection

Question 13

What big concern do we have for Primaquine?

Answer 13

Test for G6PD deficiency to avoid hemolytic reactions!

Question 14

What antifolates and sulfas do we use?

Answer 14

Antifolate - Proguanil, pyrimethamine

Sulfa - Suldadoxine, trimethoprim

Question 15

How do antifolates and sulfas work?

Answer 15

Inhibit dihydropterate synthase/reductase to stop nucleic acid synthesis.

Question 16

How did resistance to sulfadoxine/pyrimethamine happen?

Answer 16

This mixture was GREAT for a long time, but it has a long half life, so low levels remained in folks for a while, allowing for point mutations on the enzymes to create resistance

Question 17

How does atovoaquone work?

Answer 17

Inhibits parasite mitichondrial electron transport

Effect potentiated when paired with proguanil (together = Malarone)

Question 18

How is resistance developed for Atovaquone and Proguanil?

Answer 18

Single Point mutation in the parasite cytochrome b gene confers resistance.

Treatment has failed in those who weigh more than 100 kg

Question 19

Typical use for Atovaquone and Proguanil?

Answer 19

We use it for prophylaxis and treatment upon return, not as a treatment in endemic areas because this is quite expensive to use (6$ per pill)

Question 20

What antibiotics do we use for Malaria?

Answer 20

• Doxycycline
• Tetracycline
• Clindamycin
• Azithromycin
• Fluoroquinolones

Question 21

How do antibiotics work on malaria?

Answer 21

Work during the blood stage with a slow killing effect (when the malaria is erupting from the liver to enter the blood stream). They target ribosomal function within the apicoplast organelle (special organelle in a malaria infected RBC).

Typically, doxy/tetra/clinda used in conjunction with quinine

Question 22

I know, guess what I’m thinking, but what do we have to remember about antibiotics as antimalarials in conjunction with treating traveler’s diarrhea?

Answer 22

If someone has malaria in them, and htey get traveler’s diarrhea (we use antibiotics to treat this), you may see a presentation where the traveler’s diarrhea goes away and then comes back with other “strange” symptoms. This is because malaria has kicked in after the antibiotic regiment ended. Keep Malaria in mind for strange presentations of common endemic gut stuff.

Question 23

How do Artemesins work?

Answer 23

Like antibiotics, these guys act during the blood stages, but they have a rapid effect vs. the slow effect of antibiotics. They act on the rings-schizonts, and the believed mechanism is through endoperoxide to produce free radicals.

Question 24

Artemether (an artemesin) combined with lumefantrime is known in the U.S. as Coartem. What do we use it for?

Answer 24

Artemesins are the most powerful thing we have against Malaria. Period. We use this combo for:
- 1st line for uncomplicated Falciparum

It’s FDA approved (yay)

Question 25

What do we use Artesunate for?

Answer 25

1st line for severe Malaria in most of the world, given IV. Not yet FDA approved (WAHHH) but we can use it thanks to the IND protocol from the CDC.

Question 26

Why are Artemesins so good for use?

Answer 26

They act on all parts of the life cycle, so it can act quickly and effectively at all times.

Question 27

For uncomplicated Malaria (the one that LOOKS complicated, i.e., fever chills headache myalgias, but the patient is still mentally with it and can tolerate meds), what ACTs do we use?

Answer 27

Artemether with lumafantrine isthe main one.

Can also use artesunate + amodiaquine, artesunate + mefloquine, and artesunate + sulfadoxine/pyrimethamine

Question 28

For severe Malaria symptoms, what do we do?

Answer 28

1. Artesunate IV
2. Quinine IV

Those are your two options, but use quinine if you need to.

Question 29

For uncomplicated disease in pregnancy, what do we use?

Answer 29

Quinine + clinda or just mefloquine.

In severe disease, use quinidine, or artesunate if they are intolerant.

Question 30

Anyone with p.falciparum –>

Answer 30

ADMIT FOR 24HOURS to ensure response to therapy

Question 31

Causal vs. suppressive prophylactic review

Answer 31

Causal –> Kills parasite in primary liver stage and blood stage (Atovaquone proguanil). Only have to use for 1 week after departure from risk area.

Suppressive –> Kills parasites in erythrocytic phase only (Mefloquine, Doxy, chloroquine). MUST HAVE DRUG IN SYSTEM AS PARASITE EMERGES (2+ week after infection)