Antimalarials Flashcards

1
Q

What do quinolines do?

A

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

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2
Q

Examples of quinolines

A
Quinine
Quinidine
Chloroquine
Hydroxychloroquine (Plaquinil) (although this is used more in rheumatology as an antimalarial)
Mefloquine
Primaquine
Lumefantrine
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3
Q

What does chloroquine not work on?

A

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

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4
Q

For quinolines, which are prophylactic vs therapeutic?

A

Chloroquine and mefloquine are the only ones for prophylaxis.

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

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5
Q

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

A

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)

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6
Q

What do we worry about with quinine and quinidine?

A

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

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7
Q

What do we tend to use chloroquine for?

A

P falciparum in Central America, Haiti, DR

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

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8
Q

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

A

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

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

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9
Q

What side effects and contraindications for mefloquine?

A
  • Cardiotoxic if used with quinine/quinidine/halofantrine (kinda dumb since quinidine already is cardiotoxic alone)
  • Neuropsychiatric side effects at treatment
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10
Q

Who do we give mefloquine to?

A

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

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11
Q

What is resistant to Mefloquine?

A

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.

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12
Q

What do we give primaquine for?

A

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

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13
Q

What big concern do we have for Primaquine?

A

Test for G6PD deficiency to avoid hemolytic reactions!

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14
Q

What antifolates and sulfas do we use?

A

Antifolate - Proguanil, pyrimethamine

Sulfa - Suldadoxine, trimethoprim

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15
Q

How do antifolates and sulfas work?

A

Inhibit dihydropterate synthase/reductase to stop nucleic acid synthesis.

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16
Q

How did resistance to sulfadoxine/pyrimethamine happen?

A

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

17
Q

How does atovoaquone work?

A

Inhibits parasite mitichondrial electron transport

Effect potentiated when paired with proguanil (together = Malarone)

18
Q

How is resistance developed for Atovaquone and Proguanil?

A

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

Treatment has failed in those who weigh more than 100 kg

19
Q

Typical use for Atovaquone and Proguanil?

A

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)

20
Q

What antibiotics do we use for Malaria?

A
  • Doxycycline
  • Tetracycline
  • Clindamycin
  • Azithromycin
  • Fluoroquinolones
21
Q

How do antibiotics work on malaria?

A

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

22
Q

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?

A

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.

23
Q

How do Artemesins work?

A

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.

24
Q

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

A

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)

25
Q

What do we use Artesunate for?

A

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.

26
Q

Why are Artemesins so good for use?

A

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

27
Q

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?

A

Artemether with lumafantrine isthe main one.

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

28
Q

For severe Malaria symptoms, what do we do?

A
  1. Artesunate IV
  2. Quinine IV

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

29
Q

For uncomplicated disease in pregnancy, what do we use?

A

Quinine + clinda or just mefloquine.

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

30
Q

Anyone with p.falciparum –>

A

ADMIT FOR 24HOURS to ensure response to therapy

31
Q

Causal vs. suppressive prophylactic review

A

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)