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Module 3 Term 4 > Antimalarials > Flashcards

Antimalarials Flashcards

1
Q

P. Vivax Incubation Period

A

2-17 days

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2
Q

P. Falciparum incubation Period

A

9-14 days

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3
Q

P. ovale Incubation Period

A

16-18 days

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4
Q

P. malarial incubation period

A

18-40 days

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5
Q

Lab diagnosis for Malria

A

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

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6
Q

Antimalarial Drugs

A
  • Chloroquine
  • Quinine and Quinidine
  • Mefloquine
  • Primaquine
  • Atovaquone
  • Sulfadoxine-pyrimethamine • Doxycycline
  • Artemisinins
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7
Q

Chloroquine Clinical Applications

A
  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
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8
Q

Chloroquine MOA

A

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

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9
Q

Chloroquine Resistance

A

P. falciparum: mutations in putative transporter, PfCRT

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10
Q

Chloroquine AE

A
  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
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11
Q

Chloroquine Contraindications

A

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

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12
Q

Quinine & Quinidine Clinical Applications

A
  1. Parenteral treatment of severe falciparum malaria (Quinidine)
  2. Oral treatment of falciparum malaria (alternative in chloroquine-resistant areas) (Quinine)
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13
Q

Quinine & Quinidine MOA

A
  1. Depresses O2 uptake and carbohydrate metabolism

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

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14
Q

Quinine & Quinidine Adverse Effects

A
  • 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)
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15
Q

Quinine & Quinidine Contraindications

A
  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
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16
Q

Mefloquine Clinical Applications

A

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

17
Q

Mefloquine AE

A
  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
18
Q

Mefloquine Contraindications

A
  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
19
Q

Primaquine Clinical Applications

A

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)
20
Q

Primaquine AE

A
  1. Infrequent (nausea, epigastric pain, abdominal cramps,
    headache)
  2. Rare (leukopenia, agranulocytosis, leukocytosis, cardiac arrhythmias)
  3. Hemolysis or methemoglobinemia (especially in G6PD deficient patients)
21
Q

Primaquine Contraindications

A
  • G6PD deficiency

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

22
Q

Malarone

A

atovaquone + proguanil

23
Q

Malarone Clinical Applications

A

Treatment & prophylaxis of P. falciparum

24
Q

Malarone MOA

A

Disrupts mitochondrial electron transport

25
Q

Malarone AE

A

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

26
Q

Inhibitors of Folate Synthesis

A
  1. Pyrimethamine
  2. Proguanil
  3. Sulfadoxine
27
Q

Inhibitors of Folate Synthesis Clinical Applications

A
  1. Chemoprophylaxis: only in combination.
  2. Treatment of chloroquine-resistant falciparum malaria : pyrimethamine-sulfadoxine commonly used. DO NOT use for severe malaria
28
Q

Inhibitors of Folate Synthesis MOA

A
  • Pyrimethamine + proguanil = inhibit plasmodial dihydrofolate reductase
  • Sulfonamides = inhibit dihydropteroate synthase
29
Q

Inhibitors of Folate Synthesis AE

A

• 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

30
Q

Doxycycline Clinical Applications

A
  • 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
31
Q

Doxycycline AE

A

• 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)

32
Q

Artemisinin Drugs

A
  • Artesunate : oral, IV, IM & rectal admin • Artemether: oral, IM & rectal admin
  • Dihydroartemisinin: oral admin
  • Coartem = artemether + lumefantrine
33
Q

Artemisinin Clinical Applications

A

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

34
Q

Artemisinin MOA

A

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

35
Q

Artemisinin AE

A
  • 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
36
Q

Clindamycin

A

Can be used as an alternative to doxycycline

37
Q

Halofantrine

A

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

38
Q

Lumefantrine

A

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

Module 3 Term 4 (3 decks)

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