Antimalarials

Question 1

Clinical cure is

Answer 1

Getting rid of symptoms by eliminating blood schizonts

Question 2

Radical cure means

Answer 2

Eliminating all plasmodia, both in the blood and liver stage

Required for ovale and vivax

Only the tissue schizonticide primaquine can provide a radical cure for these two.

Question 3

P. falciparum

Answer 3

Most common and also most lethal form of malaria

Fever recurs every 3rd day

Can cause cerebral malaria by clogging small blood vessels in brain

No secondary tissue forms (radical cure with blood schizonticide)

Question 4

P. vivax

Answer 4

Benign tertian malaria

Has secondary tissue form (hypnozoites) —> relapses

Question 5

P. ovale

Answer 5

Rare

has hypozoite as well

Question 6

P. malaria

Answer 6

Rare, no secondary tissue form

Question 7

Three guiding factors for malaria treatment

Answer 7

1. What plasmodium species?
2. Clinical status of the patient (complicated or uncomplicated? Oral v Parenteral)
3. Drug susceptibility of infecting parasites? Travel Hx and whether they were on prophylaxis

Question 8

DOC* blood schizonticide for malaria

Answer 8

Chloroquine (Aralen) - declining in use b/c of resistance

Question 9

For the treatment of chloroquine-resistant malaria:

Answer 9

DOC:
ACT drug AND either Atovoquone/proguanil (Malarone) or Lumefantrine (Coartem)
Next:
Quinine AND either doxycycline, tetracycline, or clindamycin
ACT + mefloquine
ACT + sulfadoxine-pyrimethamine (Fandisar)

Question 10

Chloroquine MOA

Answer 10

Actively concentrated within plasmodia food vacuole —> interferes with lysosomal degradation of hemoglobin

Oral, well absorbed (though inhibited by Mg2+ and Ca2+)

Accumulates in melanin-rich tissues (skin, retina)

Metabolized by liver, substrate of CYP3A4

Can be used once weekly for prophylaxis b/c long duration of action

Question 11

Chloroquine toxicity

Answer 11

Retinal and corneal toxicity
Hemolysis - caution in G6PD deficient patients
Increased risk for QT prolongation
Contraindicated for pt with psoriasis and porphyria (b/c increases attacks)

Question 12

ACT drugs

Answer 12

Artemisinins: Artesunate and Artemether
Almost TOO good - work really well and eliminated really quickly, therefore high risk for resistance so ALWAYS use in combo

Cannot be obtained INDIVIDUALLY in the US but CDC has some

Question 13

Artemisinin Combination Treatment (ACT)

Answer 13

NEVER monotherapy
DOC: Artesunate + Atovoquone-proguanil (malarone)
Artemether + lumefantrine (coartem)
Drug of last resort: Artesunate + mefloquine
In pregancy: Artesunate + sulfadoxine-pyrimethamine (Fansidar)

Question 14

Sulfadoxine and proguanil both work on the same pathway as sulfa drugs

Answer 14

PABA in folate metabolism

Question 15

Atovaquone + proguanil (Malarone)

Answer 15

Atovaquone - interferes with mitochondrial electron transport, ATP, and pyramiding biosynthesis
Proguanil - prodrug that is a folate reductase inhibitor
Synergistic combo - great in areas of chloroquine resistance
Combined with Artesunate for rapid clearance and decrease in resistance

Caution when used by pregnant women (need leucovorin supplement)

Question 16

Lumefantrine (Coartem)

Answer 16

Given in combo with Artemether
Long-acting, oral

Toxicity - headache in 56%, QT prolongation

Question 17

Quinine and Quinidine Gluconate

Answer 17

Quinidine (given IV) is a stereoisomers of quinine (oral)
An option for treatment of complicated, chloroquine-resistant malaria
Combine with doxy, tetracycline, or clindamycin to reduce the length of treatment

VERY toxic (narrow margin between therapeutic and toxic dose)

Question 18

Quinine toxicity

Answer 18

Cinchonism - tinnitus, headache, dizziness, flushing, visual disturbances
Antiarrhythmic agent - class1A
QT elongation
Diarrhea
Hemolysis in G6PD deficient patients

Question 19

Antibiotics for malaria treatment

Answer 19

Tetracycline, doxycycline, clindamycin
Not for use in pregnant women or children
Combined with quinidine gluconate or quinine for the treatment of complicated, chloroquine-resistant malaria
Tetracyclines more effective than clindamycin
Doxy can be used for prophylaxis (daily)

Question 20

Mefloquine (Lariam)

Answer 20

Used for treatment of chloroquine-resistant malaria
Orally, very slowly excreted (single dose treatment)

TOXIC - depression of the myocardium, seizures, aggravate latent psychoses
DO NOT USE in any patient with mental illness or epilepsy

Question 21

Pyrimethamine plus sulfadoxine (Fansidar)

Answer 21

Used for empirical treatment and preventative intermittent therapy in PREGNANT WOMEN

Combined with Artesunate

Potential for toxicity and allergic reactions like other sulfas

Not available in US

Question 22

Primaquine

Answer 22

The ONLY tissue schizonticide, for use vs. vivax or ovale to achieve radical cure (terminal prophylaxis)

Must also use with blood schizonticide to treat symptoms (won’t suppress disease once developed)

Question 23

Primaquine contraindications and toxicities

Answer 23

Contra in SLE or rheumatoid arthritis —> granulocytes Elia

Hemolytic anemia in G6PD deficiency (use at low dose for longer period)

DO NOT use in pregnancy because you don’t know the G6PD status of the fetus