Antimalarials

Question 1

P. Vivax Incubation Period

Answer 1

2-17 days

Question 2

P. Falciparum incubation Period

Answer 2

9-14 days

Question 3

P. ovale Incubation Period

Answer 3

16-18 days

Question 4

P. malarial incubation period

Answer 4

18-40 days

Question 5

Lab diagnosis for Malria

Answer 5

Thick or thin smear. Thick for parasite, thin for gametocytes

Question 6

Antimalarial Drugs

Answer 6

• Chloroquine
• Quinine and Quinidine
• Mefloquine
• Primaquine
• Atovaquone
• Sulfadoxine-pyrimethamine • Doxycycline
• Artemisinins

Question 7

Chloroquine Clinical Applications

Answer 7

1. Drug of choice in the treatment of non-falciparum and sensitive uncomplicated falciparum malaria
2. Preferred chemoprophylactic agent in areas without resistant falciparum malaria

Question 8

Chloroquine MOA

Answer 8

Prevents biocrystallization of hemoglobin breakdown product heme to non-toxic hemozoin

Question 9

Chloroquine Resistance

Answer 9

P. falciparum: mutations in putative transporter, PfCRT

Question 10

Chloroquine AE

Answer 10

1. Pruritus (common in Africans)
2. Nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, urticaria (uncommon)
3. Hemolysis (G6PD-deficient people)
4. Can cause electrocardiographic changes

Question 11

Chloroquine Contraindications

Answer 11

• psoriasis or porphyria (may precipitate attacks), retinal or visual field abnormalities.
SAFE IN PREGNANCY & YOUNG CHILDREN

Question 12

Quinine & Quinidine Clinical Applications

Answer 12

1. Parenteral treatment of severe falciparum malaria (Quinidine)
2. Oral treatment of falciparum malaria (alternative in chloroquine-resistant areas) (Quinine)

Question 13

Quinine & Quinidine MOA

Answer 13

1. Depresses O2 uptake and carbohydrate metabolism

2. Intercalates into DNA, disrupting parasite’s replication and transcription

Question 14

Quinine & Quinidine Adverse Effects

Answer 14

• Cinchonism: tinnitus, headache, nausea, dizziness, flushing & visual disturbances
• Hypersensitivity: skin rashes, urticaria, angioedema, bronchospasm
• Hematologic abnormalities: hemolysis (G6PD deficiency), leukopenia, agranulocytosis, thrombocytopenia
• Hypoglycemia: stimulation of insulin release
• Uterine contractions: still used in treatment of severe falciparum malaria in pregnancy
• Severe hypotension: too rapid IV infusion
• ECG abnormalities: QT prolongation
• Blackwater fever: hemolysis & hemoglobinuria (likely hypersensitivity reaction)

Question 15

Quinine & Quinidine Contraindications

Answer 15

1. Do not use concurrently with mefloquine
2. Can raise plasma levels of warfarin & digoxin
3. Reduce dose in renal insufficiency
4. FDA category C in pregnancy

Question 16

Mefloquine Clinical Applications

Answer 16

Effective against many chloroquine-resistant strains
• Chemoprophylaxis: effective against most strains of P. falciparum and P.vivax
• Currently only medication recommended for chemoprophylaxis in pregnant women in chloroquine-resistant areas
• Treatment : can be used to treat mild to moderate acute malaria caused by P.falciparum and P.vivax
• Mefloquine + artesunate used in treatment of uncomplicated malaria in regions of Southeast Asia

Question 17

Mefloquine AE

Answer 17

1. Serious neurological and psychiatric toxicities:
   Dizziness, loss of balance, ringing in the ears, anxiety, depression, hallucinations
2. Weekly dosing: Nausea, vomiting, diarrhea, dizziness, sleep & behavioral disturbances, rash
3. Higher treatment doses:
   Leukocytosis, thrombocytopenia, aminotransferase elevations, arrhythmias, bradycardia

Question 18

Mefloquine Contraindications

Answer 18

1. Patients with history of:
   Epilepsy, psychiatric disorders, arrhythmia, cardiac conduction defects, sensitivity to related drugs
2. DO NOT coadminister with quinine, quinidine or halofantrine

Question 19

Primaquine Clinical Applications

Answer 19

Drug of choice for eradication of dormant liver forms of P. vivax and P. ovale.

1. Therapy of acute vivax and ovale malaria
2. Terminal prophylaxis of vivax and ovale malaria
3. Chemoprophylaxis: protection against falciparum & vivax (toxicities are a concern – reserved for when other drugs cannot be used)

Question 20

Primaquine AE

Answer 20

1. Infrequent (nausea, epigastric pain, abdominal cramps,
   headache)
2. Rare (leukopenia, agranulocytosis, leukocytosis, cardiac arrhythmias)
3. Hemolysis or methemoglobinemia (especially in G6PD deficient patients)

Question 21

Primaquine Contraindications

Answer 21

• G6PD deficiency

* Pregnancy: fetus is relatively G6PD deficient DO NOT use during pregnancy

Question 22

Malarone

Answer 22

atovaquone + proguanil

Question 23

Malarone Clinical Applications

Answer 23

Treatment & prophylaxis of P. falciparum

Question 24

Malarone MOA

Answer 24

Disrupts mitochondrial electron transport

Question 25

Malarone AE

Answer 25

Abdominal pain, nausea, vomiting, diarrhea, headache, rash. Do not use in pregnancy

Question 26

Inhibitors of Folate Synthesis

Answer 26

1. Pyrimethamine 2. Proguanil 3. Sulfadoxine

Question 27

Inhibitors of Folate Synthesis Clinical Applications

Answer 27

1. Chemoprophylaxis: only in combination. 2. Treatment of chloroquine-resistant falciparum malaria : pyrimethamine-sulfadoxine commonly used. DO NOT use for severe malaria

Question 28

Inhibitors of Folate Synthesis MOA

Answer 28

* Pyrimethamine + proguanil = inhibit plasmodial dihydrofolate reductase * Sulfonamides = inhibit dihydropteroate synthase

Question 29

Inhibitors of Folate Synthesis AE

Answer 29

• Well tolerated (GI problems, rashes, itching) • Proguanil (mouth ulcers, alopecia = rare) • Pyrimethamine-Sulfadoxine (erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis) • Sulfadoxine (hematologic, GI, CNS, dermatologic & renal toxicity) Pregnancy • Proguanil = safe • Pyrimethamine-sulfadoxine = safe

Question 30

Doxycycline Clinical Applications

Answer 30

* Used to complete treatment for severe falciparum malaria (given along with quinine) after initial treatment with quinine, quinidine or artesunate * Chemoprophylaxis against most forms: must be taken daily

Question 31

Doxycycline AE

Answer 31

• GI, candidal vaginitis, photosensitivity • Discoloration & hypoplasia of teeth, stunting of growth • Fatal hepatotoxicity (in pregnancy) • DO NOT use in pregnancy or children < 8y (FDA Category D)

Question 32

Artemisinin Drugs

Answer 32

* Artesunate : oral, IV, IM & rectal admin • Artemether: oral, IM & rectal admin * Dihydroartemisinin: oral admin * Coartem = artemether + lumefantrine

Question 33

Artemisinin Clinical Applications

Answer 33

• Treatment of severe falciparum malaria (given IV). Should not be used as single agent to protect against resistance

Question 34

Artemisinin MOA

Answer 34

Binds iron, breaking down peroxide bridges leading to generation of free radicals that damage parasite proteins.

Question 35

Artemisinin AE

Answer 35

* Overall remarkably safe (nausea, vomiting, diarrhea) * Very high doses: neurotoxicity, QT prolongation * More evidence for use in 2nd and 3rd trimesters of pregnancy * In 1st trimester can be used for treatment of severe malaria

Question 36

Clindamycin

Answer 36

Can be used as an alternative to doxycycline

Question 37

Halofantrine

Answer 37

• Use is limited by irregular absorption & cardiac toxicity • Teratogenic

Question 38

Lumefantrine

Answer 38

• Available only as fixed-dose combination with artemether • Causes minor QT prolongation (clinically insignificant)