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Antimalarial Flashcards

1
Q

Cause of malaria

A

Plasmodia species

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2
Q

4 plasmodia species

A

P. vivax, P. ovale, P. falciparum, P. malariae

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3
Q

Malaria transmission cycle

A

Inject sporozoites –> Liver/tissue stage: schizont infect hepatocyte, replicate and then rupture (vivax and ovale can remain dormant in hepatocyte) –> all 4 go into blood stream, infect RBC and go through asexual stages and rupture RBC (stage where u see sx) –> cycle continues, mosquito can infect someone else

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4
Q

What causes sx of malaria (fever/chills)

A

RBC rupture

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5
Q

Clinical cure

A

getting rid of sx.; eliminating schizont in blood stream

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6
Q

Radical cure

A

eliminating all plasmodia in blood and liver stage

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7
Q

Plasmodia in liver stage

A

vivax and ovale

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8
Q

Most lethal form

A

P. falciparum

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9
Q

Most common form

A

P. vivax

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10
Q

Hypnozoites

A

Vivax and ovale

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11
Q

Blood plasmodia

A

falciparum, malariae

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12
Q

Malaria sx

A

H/A, fever, fatigue, pain, chills, sweating, dry cough, splenomegaly, N/V

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13
Q

Blood schizonticides

A

can on erythrocytic forms of the parasite; provide clinical cure; do not effect 2ndary tissue forms (vivax and ovale)

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14
Q

Tissue schizonticide

A

eliminate from tissue; act on hepatic stages; don’t suppress symptoms once erythrocytic stages have been established; prevent relapse

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15
Q

Prevention of mosquito bites

A

permethrin - cover netting, tents, clothes etc.

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16
Q

Blood Schizonticide examples

A

chloroquine, hydroxychloroquine
quinine sulfate and quinidine gluconate
doxycycline, clindamycin
Artemisinin - Artesunate OR artemether + atovagquone-proguanil, lumefantrine, pyrimethamine-sulfadoxine, mefloquine

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17
Q

DOC for malaria

A

Chloroquine - but big drug resistance

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18
Q

Chloroquine resistant malaria

A
  1. Artesunate + atovoquone/proguanil OR artemether-lumefantrine
  2. Quinine
  3. Artesunate + mefloquine
  4. Artesunate + sulfadoxine-pyrimethamine
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19
Q

Chloroquine

A

DOC for sensitive organisms;
prophylaxis for sensitive org.
Resistant forms (falciparum)

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20
Q

Resistance to chloroquine

A

transport pump

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21
Q

Chloroquine MOA

A

actively concentrated w/i plasmodia that reside w/i erythrocytes; may interfere w/ lysosomal degradation of Hb (hemazoin builds up and is detrimental)

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22
Q

Chloroquine kinetics

A

oral
Well absorbed from GI (Mg and Ca inhibit)
Accumulates in melanin-rich tissues (skin, retina)
metabolized by liver; substrate of CYP3A4
Excreted in urine
Long duration of action - once weekly for prophylaxis

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23
Q

Chloroquine toxicity

A 
CNS
GI
Retinal and corneal toxicity*** ototoxicity (seen w/ high, chronic dose - rheumatologic disease; contra in ocular disease)
immunologic- skin rash, pruritis
Hemolysis**- G6PD
QT prolongations
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24
Q

Hemolysis in G6PD

A

INH, Chloroquine

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25
Q

Contraindications for Chlorouine

A

ocular disease
psoriasis
porphyria

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26
Q

Artemisins

A

Artesunate and artemether

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27
Q

Artemisin qualities

A

most rapid action of all drugs against P. falciparum; always combine w/ other antimalarial to avoid high recrudescence
oral
unknown MOA
Not on market in US - can get formulations (combo)

28
Q

ACT treatment

A

Artemisinin Combination Treatment; used for chloroquine resistant malaria

29
Q

ACT combinations

A
  1. Artesunate + Atovoquone-proguanil
  2. Arthemeter + lumefantrine
  3. Artesunate + mefloquine
  4. Artesunate _+ sulfadoxine-pryimethamine
30
Q

When is artesunate + sulfadoxine-pryimethamine used

A

empirical tx or in pregnancy

31
Q

Inhibit folate metabolism

A

Proguanil

prymiethamine-sulfadoxine

32
Q

Resistance to proguanil and sulfadoxine

A

mutations in DHFR

33
Q

Proguanil; sulfadoxine mechanism

A

inhibit folate metabolism;
sulfadoxine inhibits incorporation of PABA into folic acid
Pyrimethamine & proguanil: inhibit DHFR, blocking convertion of DHFA to THFA; plasmodial enzyme more sensitive than human enzyme

34
Q

Atovaquone MOA

A

interferes w/ mitochondrial electron transport and ATP and pyrimidine biosynthesis

35
Q

Proguanil

A

prodrug; converted to cycloguanil - dyhydrofolate reductase inhibitor

36
Q

Atovaguone + proguanil

A

ORAL; synergistic; combined with artesunate for rapid clearance and decrease in resistance

37
Q

When is artesunate + atovaquone + proguanil used

A

uncomplicated chloroquine resistant malaria and prophylaxis for resistant regions

38
Q

Side effects of atovaquone + proguanil

A

rash, fever, vomiting, diarrhea

Caution in pregnant women- cycloquanil (active metabolite of proguanil) may be mutagenic (GIVE LEUCOVORIN)

39
Q

Leucovorin

A

give with proguanil; allows folate synthesis to be rescued

40
Q

Lumefantrine

A

used in combo with artemether; ORAL
MOA unknown;
long-acting

41
Q

Toxicity of lumefantrine

A

H/A (56%), dizziness, anorexia, nausea

QT prolongation**

42
Q

QT prolongation

A

chloroquine
Lumefantrine
Quinine

43
Q

Stereoisomer of quinine

44
Q

Tx of COMPLICATED chloroquine-resistant plasmodia

A

Quinine + doxycycline, tetracycline or clindamycin (reduces length of tx and side effects)

45
Q

Kinetics of quinine

A

oral
half-life: 5-16 hours
Quinidine gluconate - oral and IV (comatosed state)
extensive liver metabolism

46
Q

antimalaria for someone in coma

A

Quinidine gluconate

47
Q

Toxicity of quinine

A

VERY TOXIC: narrow margin b/w effective dose and toxic dose

cinchonism- tinnitus, H/A, dizziness, flushing, visual disturbance
Antiarrhythmic agent - class 1A
QT elongation
GI, Diarrhea*, N/V
Hemolysis (G6PD)
Stimulate insulin release- caution in those with hypoglycemia

48
Q

Tx of complicated, chloroquine resistance malaria in pregnant women/children

A

Quinine + clindamycin

49
Q

Combo with quinine

A 
tetracycline preferred (better than clindamycin)
Doxycycline can be used for prophylaxis against MDR malaria - taken daily
50
Q

Mefloquine

A

useful for chloroquine-resistant strains; unknown MOA

Resistance and TOXICITY limit use

51
Q

Mefloquine kinetics

A

oral
good bioavailability, absorbed from GI
distributed to blood, urine, CSF, tissue and erythrocytes
Metabolized by liver
Eliminated SLOWLY- single dose treatment***

52
Q

Mefloquine toxicity

A

N/V
Ab pain, anorexia, diarrhea
arthralgia, myalgia, chills gatigue, fever
DEPRESSION OF MYCOCARDIUM (cardic toxicity; do not combine with quinine)
Can cause seizures and may aggravate latent psychoses **
vivid dreams

53
Q

Contraindication of mefloquine

A

Hx of mental illness or epilepsy

Pregnancy - teratogenicity

54
Q

Severe aggravation of psychoses

A

Mefloquine

55
Q

Mefloquine is combined with

A

Artesunate

56
Q

Pyrimethamine plus sulfadoxine use

A

oral; empirical tx and preventative intermittent therapy in pregnant women; combined w/ artesunate

57
Q

Pyrimethamine + sufadoxine toxicity

A

sulfa toxicities and allergic reactions; SJS, TEN

58
Q

Only tissue schizonticide

A

Primaquine

59
Q

primaquine facts

A

ONLY active against tissue forms (exoerythrocytic) and gametocytes
Will not suppress disease once developed
oral
unknown MOA; increasing resistance

60
Q

Radical cure for vivax and ovale

A

Primaquine; used for terminal prophylaxis (presumptive antirelapse therapy)

61
Q

Primaquine toxicity

A

mild, but increases with chronic usage:

GI
CNS- H/A, dizzy
Contra: SLE, RA, granulocytopenia
HEMOLYTIC ANEMIA** (G6PD- not contra though)
Not recommended for prego, infants >6 months, breastfeeding- fetal hemolytic anemia (treat prego with chloroquine until birth then give radical cure)

62
Q

contraindications for primaquine

A

SLE, RA, granulocytopenia

63
Q

Prolonged QT

A

Chloroquine
Lumefantrine
Quinine

64
Q

Hemolytic anemia

A

Chloroquine
Quinine
Primaquine

65
Q

Fetal hemolytic anemia

A

Primaquine

Pharm Final (6 decks)

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