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Flashcards in Antimalarials Deck (70)
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1

describe plasmodiums pre-erythrocytic stage in its life cycle, 

what is the infective form?

  • sporozoite = infective form
  • asymptomatic for up to 1 month
  • invades and matures in hepatocytes → schizonts

2

describe plasmodiums erythrocytic stage in its life cycle

  • ​schizonts rupture into merozoites
  • merozoites go into blood stream → invade RBC's where they form trophozoites
  • trophozoites mature into schizonts 
  • schizonts digest hemoglobin and rupture into merozoites again → RBC lysis releases them

3

describe "cyclic fevers" 

  • "cyclic fevers" → plasmodium stages cycles occur every 2-3 days
  • vivax/ovale: 48 hr cycles (fever on days 1 + 4)
  • malaria/falciparum: 72 hr cycles 

4

describe p. falciparum & p. malariae life cycle 

  • only 1 cycle of liver cell invasion 
  • liver infection stops in < 4 weeks
  • only erythrocytic parasites have to be eliminated 

5

describe p. vivax & p. ovale life cycle 

  • have a dormant hepatic stage
  • erythrocytic and hepatic parasites have to be eliminated 

6

describe malarial paroxysm 

  • occurs every 2-3 days once infection is established
    • ​fever
    • anemia
    • jaundice
    • splenomegaly
    • hepatomegaly

7

describe p. falciparum and its symptoms 

  • most severe disease (microvascular effects)
  • fatal if untreated
  • cerebral malaria (irritability → seizures → coma)
  • symptoms
    • respiratory distress syndrome 
    • diarrhea
    • severe thrombocytopenia
    • spont. abortion
    • hypoglycemia 

8

when treating malaria, treatment should be guided by:

  1. type of plasmodium species infected 
    • falciparum: rapid illness/death
    • vivax/ovale: treat hypnozoites dormant in liver 
  2. clinical status of the patient
    • uncomplicated malaria: treat w/ oral antimalarials
    • complicated malaria: treat aggressively with parenteral antimalarials 
  3. drug susceptibility of infecting parasite 
    • falciparum/vivax: different resistance patterns in different geographic areas 

9

DOC for treatment, prophylaxis of p. vivax/ovale, and sensitive uncomplicated p. falciparum malaria 

chloroquine

10

Chloroquine is highly effective against ____ parasites but not ____ parasites 

Chloroquine is highly effective against blood parasites but not liver parasites 

11

describe chloroquine's MOA 

  • concentrates in parasite food vacuoles
  • blocks heme polymerase → hemoglobin breakdown of heme cannot be made into non-toxic hemazoin

12

describe chloroquine PK and resistance

  • oral, half life: 3-5 days → taken once weekly 
  • P. falciparum: mutations in putative transporter PfCRT

13

describe chloroquine AEs

  • generally well tolerated
  • pruritis (common in africans) 
  • nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, urticaria (uncommon)
  • hemolysis (G6PD-deficient people)
  • can cause electrocardiographic changes

14

Chloroquinine is contraindicated in patients with

  • psoriasis or porphyria (may precipitate attacks)
  • retinal or visual field abnormalities

15

is chloroquine safe to use in pregnancy or children? 

yes! 

16

what is 1st line therapy for severe falciparum disease? 

quinine / quinidine 

17

what is the difference between quinine and quinidine? 

  • quinine
    • oral treatment of falciparum malaria 
  • quinidine 
    • parenteral treatment for severe falciparum malaria (D for death! = more severe!) 

18

quinine/quinidine are rapidly-acting, highly effective against ___ parasites, but NOT active against ___ parasites

quinine/quinidine are rapidly-acting, highly effective against blood parasites, but NOT active against liver parasites

19

describe quinine/quinidine MOA 

  • Depresses O2 uptake and carbohydrate metabolism
  • Intercalates into DNA, disrupting parasite replication and transcription

20

describe quinine/quinidine AEs

  • 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
  • QT prolongation
  • Blackwater fever: hemolysis & hemoglobinuria

21

quinine/quinidine contraindications

  • Discontinue if signs of: severe cinchonis, hemolysis, hypersensitivity
  • Avoid in pts with visual or auditory problems
  • Use with caution in patients with:
    • underlying cardiac abnormalities
  • Can raise plasma levels of warfarin & digoxin
  • Reduce dose in renal insufficiency
  • Pregnancy category C however use in complicated malaria b/c benefits outweight risks

22

quinine/quinidine should NOT be used concurrently with

mefloquine

23

mefloquine is effective against _____ strains 

mefloquine is effective against chloroquine-resistant strains

24

describe mefloquines MOA 

destruction of the asexual blood forms of malarial pathogens

details unknown (thank god..) 

25

___ is the only medication recommended for chemoprophylaxis in pregnant women in chloroquine-resistant areas

mefloquine is the only medication recommended for chemoprophylaxis in pregnant women in chloroquine-resistant areas

26

___ and ____ are used in treatment of uncomplicated malaria in regions of Southeast Asia

mefloquine and artesunate are used in treatment of uncomplicated malaria in regions of Southeast Asia

27

describe mefloquine pharmokinetics 

  • oral only
  • t1/2 = 20 days 
    • weekly prophylactic dosing 

28

describe mefloquine AEs

  • serious neurological and psychiatric toxicities:
    • dizziness, loss of balance
    • ringing in the ears
    • anxiety, depression
    • hallucinations

29

contrast mefloquine AEs with weak vs high dosing 

  • weak dose
    • nausea, vomiting, diarrhea
    • dizziness
    • sleep and behavioral disturbances
    • rash
  • high dose
    • leukocytosis
    • thrombocytopenia
    • aminotransferase elevations
    • arrhythmias
    • bradycardia

30

mefloquine is contraindicated in patients with history of

  • epilepsy
  • psychiatric disorders
  • arrhythmia, cardiac conduction defects
  • sensitivity to related drugs