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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
Contraindications for Chlorouine
ocular disease psoriasis porphyria
26
Artemisins
Artesunate and artemether
27
Artemisin qualities
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
ACT treatment
Artemisinin Combination Treatment; used for chloroquine resistant malaria
29
ACT combinations
1. Artesunate + Atovoquone-proguanil 2. Arthemeter + lumefantrine 3. Artesunate + mefloquine 4. Artesunate _+ sulfadoxine-pryimethamine
30
When is artesunate + sulfadoxine-pryimethamine used
empirical tx or in pregnancy
31
Inhibit folate metabolism
Proguanil | prymiethamine-sulfadoxine
32
Resistance to proguanil and sulfadoxine
mutations in DHFR
33
Proguanil; sulfadoxine mechanism
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
Atovaquone MOA
interferes w/ mitochondrial electron transport and ATP and pyrimidine biosynthesis
35
Proguanil
prodrug; converted to cycloguanil - dyhydrofolate reductase inhibitor
36
Atovaguone + proguanil
ORAL; synergistic; combined with artesunate for rapid clearance and decrease in resistance
37
When is artesunate + atovaquone + proguanil used
uncomplicated chloroquine resistant malaria and prophylaxis for resistant regions
38
Side effects of atovaquone + proguanil
rash, fever, vomiting, diarrhea | Caution in pregnant women- cycloquanil (active metabolite of proguanil) may be mutagenic (GIVE LEUCOVORIN)
39
Leucovorin
give with proguanil; allows folate synthesis to be rescued
40
Lumefantrine
used in combo with artemether; ORAL MOA unknown; long-acting
41
Toxicity of lumefantrine
H/A (56%), dizziness, anorexia, nausea | QT prolongation**
42
QT prolongation
chloroquine Lumefantrine Quinine
43
Stereoisomer of quinine
quinidine
44
Tx of COMPLICATED chloroquine-resistant plasmodia
Quinine + doxycycline, tetracycline or clindamycin (reduces length of tx and side effects)
45
Kinetics of quinine
oral half-life: 5-16 hours Quinidine gluconate - oral and IV (comatosed state) extensive liver metabolism
46
antimalaria for someone in coma
Quinidine gluconate
47
Toxicity of quinine
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
Tx of complicated, chloroquine resistance malaria in pregnant women/children
Quinine + clindamycin
49
Combo with quinine
``` tetracycline preferred (better than clindamycin) Doxycycline can be used for prophylaxis against MDR malaria - taken daily ```
50
Mefloquine
useful for chloroquine-resistant strains; unknown MOA | Resistance and TOXICITY limit use
51
Mefloquine kinetics
oral good bioavailability, absorbed from GI distributed to blood, urine, CSF, tissue and erythrocytes Metabolized by liver Eliminated SLOWLY- single dose treatment***
52
Mefloquine toxicity
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
Contraindication of mefloquine
Hx of mental illness or epilepsy | Pregnancy - teratogenicity
54
Severe aggravation of psychoses
Mefloquine
55
Mefloquine is combined with
Artesunate
56
Pyrimethamine plus sulfadoxine use
oral; empirical tx and preventative intermittent therapy in pregnant women; combined w/ artesunate
57
Pyrimethamine + sufadoxine toxicity
sulfa toxicities and allergic reactions; SJS, TEN
58
Only tissue schizonticide
Primaquine
59
primaquine facts
ONLY active against tissue forms (exoerythrocytic) and gametocytes Will not suppress disease once developed oral unknown MOA; increasing resistance
60
Radical cure for vivax and ovale
Primaquine; used for terminal prophylaxis (presumptive antirelapse therapy)
61
Primaquine toxicity
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
contraindications for primaquine
SLE, RA, granulocytopenia
63
Prolonged QT
Chloroquine Lumefantrine Quinine
64
Hemolytic anemia
Chloroquine Quinine Primaquine
65
Fetal hemolytic anemia
Primaquine

Pharm Final (6 decks)

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