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Pharmacology Test #2 > Antimalarials > Flashcards

Antimalarials Flashcards

1
Q

Five human malaria parasites

A 
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
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2
Q

Which malaria parasite is responsible for the most malaria deaths?

A

Plasmodium falciparum

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3
Q

Which malaria parasites cause relapsing malaria?

A

Plasmodium vivax

Plasmodium ovale

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4
Q

Which malaria parasite has a 24 h life cycle?

A

Plasmodium knowlesi

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5
Q

Which malaria parasite is predominant in the tropics

A

Plasmodium falciparum

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6
Q

Which malaria parasite is common in subtropics and temperate regions?

A

Plasmodium vivax

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7
Q

Which malaria parasite is found in West Africa?

A

Plasmodium ovale

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8
Q

Which malaria parasites have 48 h life cycles in the blood?

A

P. falciparum
P. vivax
P. ovale

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9
Q

Which malaria parasite has a 72 h life cycle in the blood?

A

P. malariae

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10
Q

Which malaria parasite do you always treat with Primaquine because of hypnozoites in the liver?

A

P. vivax and P. ovale

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11
Q

What’s the name of the mosquito that does malaria?

A

anopheles mosquito

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12
Q

Classic symptoms of uncomplicated malaria?

A

cold stage, hot stage, sweating stage, fever and flu-like symptoms (chills, headache, myalgias, and malaise)
anemia and jaundice

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13
Q

Symptoms of severe malaria?

A 
serious organ failure, including kidney
cerebral malaria
severe anemia and hemoglobinuria
acute respiratory distress syndrome
placental malaria
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14
Q

Describe cerebral malaria

A

abnormal behavior, impairment of consciousness, seizures, coma or other neurologic abnormalitites

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15
Q

Describe placental malaria

A

Happens especially during first pregnancy

Causes low birth weight and miscarriage

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16
Q

Tissue schizonticides

A

kills liver stage parasites

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17
Q

Blood schizonticides

A

kills erythrocytic forms

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18
Q

Gametocytocides

A

Kills sexual stages

Blocks transmission

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19
Q

Factors to consider with malaria chemoprophylaxis

A

species present
level and type of drug resistance
lead time before travel

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20
Q

Malarone

A

Atovaquone + Proguanil
All areas
Start 1-2 d prior and continue 7 d after
daily admin + short pretreatment

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21
Q

Doxycycline

A

All areas

Start 1-2 d prior and continue 4 weeks

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22
Q

Chloroquine

A

Aralen and generic
Chloroquine sensitive areas (Central/South America)
start 1-2 wk prior and continue 4 wk after leave area

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23
Q

Mefloquine

A

Lariam and generic
Mefloquine sensitive areas
start >2 wk early and continue 4 wks
toxicity issues

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24
Q

Primaquine

A

if >90 P. vivax in area

start 1-2 d prior and continue 7 d after

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25
Q

Considerations for malaria treatment

A

type (species) of the infecting parasite
area where the infection was acquired and its drug-resistance status
clinical status of the patient

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26
Q

Treatment of uncomplicated malaria infection with P. vivax or P. ovale (hypnozoites in liver) in a CQ sensitive area?

A
  1. Chloroquine [Aralen and generic] or

2. Hydroxychloroquine sulfate [Plaquenil] + primaquine (14d)

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27
Q

Treatment of uncomplicated malaria infection with P vivax or P ovale in a CQ resistant area?

A
  1. Quinine sulfate + Doxycycline/Tetracycline + Primaquine OR
  2. Atovaquone + Proguanil [Malarone] + Primaquine OR
  3. Mefloquine [Lariam and generic] + Primaquine
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28
Q

Treatment of uncomplicated malaria with P. malariae or P. knowlesi?

A
  1. Chloroquine [Aralen and generic] OR

2. Hydroxychloroquine sulfate [Plaquenil]

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29
Q

In general, what do you use in chloroquine sensitive areas for uncomplicated/unidentified species?

A

Chloroquine [Aralen] and Hydroxychloroquine sulfate [Plaquenil]

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30
Q

In general, what do you use in chloroquine resistant areas for an uncomplicated/unidentified malaria infection?

A
  1. Malarone [Atovaquone + Proguanil]
  2. Coartem [Artemether + lumefantrine]
  3. Quinine sulfate + Doxycycline/Tetracycline/Clindamycin
  4. Lariam [Mefloquine]
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31
Q

Complicated (severe) malaria

A

impaired consciousness/coma, severe monocytic anemia, renal failure, pulmonary edema

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32
Q

Treatment for complicated (severe) malaria?

A

Quinindine glyconate (IV) + doxycycline/tetracycline/clindamycin

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33
Q

What should you monitor in severe/complicated malaria?

A 
blood pressure (hypotension)
cardiac function (widening of QRS complex and/or lengthening of the QTc interval)
blood glucose (hypoglycemia)
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34
Q

Treatment of complicated/severe malaria if quinidine gluconate not available or not tolerated?

A

Artesunate followed by malarone, doxycycline/clindamycine, or mefloquine

35
Q

Artemisinin

A

Sesquiterpene lactone endoperoxide

endoperoxide is the active group

36
Q

Mechanism of action for artemisinin?

A

must be activated likely via heme-iron

activated artemisinin may form free radicals (target parasite proteins and lipids)

37
Q

Mechanism of resistance for artemisinin?

A

mutations in Kelch 13 gene

delays progress through the life cycle and may alter stress response

38
Q

Why is artemisinin not appropriate for chemoprophylaxsis?

A

It has a short half-life (1-2 h) and recrudescence rate is high after short course of treatment

39
Q

Where in the body does artemisinin act?

A

rapidly acting blood schizonticide (no effect on liver stages)

40
Q

What is artemisinin commonly paired with?

A

Mefloquine or lumefantrine

41
Q

Semisynthetic artemisinins that have an oral route of administration?

A

dihydroartemisinin
artesunate
artemether

42
Q

Semisynthetic artemisinins that have an intramuscular route of administration?

A

artesunate

artemether

43
Q

Semisynthetic artemisinin that has an intravenous route of administration?

A

artesunate (available in US via CDC for treatment of severe malaria)

44
Q

Semisynthetic artemisinin that has a rectal route of administration?

A

artesunate

45
Q

What kind of drugs are artemisinin derivatives paired with?

A

paired with longer half-life drugs

46
Q

Common artemisinin combination therapies?

A

Lumefantrine [Coartem]
amodiaquine
mefloquine
Piperaquine

47
Q

Artemisinin adverse effects

A

well tolerated
nausea, vomiting, diarrhea, and dizziness
embryotoxic in animal studies (not recommended in 1st trimester for uncomplicated malaria)

48
Q

4-aminoquinolines

A

Quinine
Chloroquine [Aralen]
Mefloquine [Lariam]

49
Q

What does chloroquine do to hemoglobin metabolism?

A

chloroquine accumulates in food vacuoles and inhibits heme polymerization

50
Q

How do 4-substituted quinolines work?

A

interfere with heme polymerization

51
Q

Initial and terminal half lives of chloroquine?

A

Initial half-life: 3 - 5 days

Terminal half-life: 1 - 2 months

52
Q

Contraindications for chloroquine

A

psoriasis or porphyria
retina or visual field abnormalities
potential for hemolysis in G6PD deficient patients

53
Q

Which drugs can interfere with the absorption of chloroquine?

A

Kaolin (antidiarrheal agent) and antacids

54
Q

Adverse effects of Chloroquine?

A

usually well tolerated
pruritus is common, especially in people of African descent
G6PD deficiency patients

55
Q

Primary mechanism of chloroquine resistance?

A

mutations in PfCRT1
localized to food vacuole
causes reduced accumulation of chloroquine
over-expression of PfMDR1 (drug transporter)

56
Q

What kind of drug is quinine?

A

Blood schizonticide

57
Q

When is quinine the treatment of choice?

A
  1. Chloroquine-resistant falciparum malaria (quinine sulfate - oral)
  2. Severe falciparum malaria (quinidine gluconate - IV)
58
Q

Why is quinine inappropriate for chemoprophylaxsis?

A

short half-life and toxicity

59
Q

Adverse effects of quinine?

A
  1. cinchonism: tinnitis, headache, nausea, dizziness, flushing and visual disturbances
  2. can stimulate uterine contractions
  3. hemolysis (G6PD deficiency)
  4. blackwater fever - severe, rare, marked by hemoglobinuria
60
Q

What can occur from too-rapid infusion of quinine?

A

severe hypotension

61
Q

What is Mefloquine [Lariam] effective against?

A

erythrocytic forms of P. falciparum and P. vivax

62
Q

Adverse effects of Mefloquine [Lariam]

A

Neuropsychiatric toxicity: seizures, toxic psychosis, sleep disturbance

63
Q

Name the other chloroquine-related compounds

A

Lumefantrine
Piperaquine
Amodiaquine
Halofantrine

64
Q

What is primaquine metabolized by?

A

CYP2D6

metabolism required for activity and may involve free radicals

65
Q

What is the drug of choice for liver stages of P. vivax and P. ovale (in combination with chloroquine)?

A

Primaquine

66
Q

Which antimalarial drug is gametocidal aginst all four malaria parasites?

A

Primaquine

67
Q

Contraindications for primaquine?

A

G6PD deficiency (hemolytic anemia)
pregnancy
breast feeding

68
Q

What stages does malarone kill?

A

kills liver and blood stages (but NOT hypnozoites)

69
Q

Which two drugs is malarone made of?

A

proguanil and atavaquone

70
Q

What is atavaquone also used to treat?

A

Toxoplasma gondii and Pneumocystis jiroveci

71
Q

What is atavaquone a selective inhibitor of?

A

selective inhibitor of malaria mitochondrial cytochrome bc1 complex (inhibits electron transport, mitochondrial membrane potential collapses)

72
Q

What is the main role for mitochondrial electron transport in P. falciparum?

A

regenerate ubiquinone

73
Q

What is atavaquone an analog of?

A

ubiquinone analog

electron acceptor for parasite dihydroorotate deydrogenase - essential for pyrimidine biosynthesis in the parasite

74
Q

What is proguanil converted to?

A

cycloguanil

75
Q

What is proguanil a selective inhibitor of?

A

selective inhibitor of the bifunctional plasmodial dihydrofolate reductase-thymidylate synthetase (crucial for parasite purine and pyrimidine synthesis)

76
Q

What does proguanil do when paired with atavaquone?

A

enhances mitochondrial toxicity of atavaquone

77
Q

What does Pyrimethamine-Sulfadoxine [Fansidar] inhibit?

A

folate synthesis inhibitor

slow acting erythrocytic schizonticide

78
Q

What does Pyrimethamine specifically inhibit?

A

inhibits plasmodia DHF-reductase (1000-fold selectivity for Plasmodium)

79
Q

First-line therapy for toxoplasmosis?

A

pyrimethamine + sulfadiazine (can be replaced with clindamycin)

80
Q

First-line therapy for pneumocystis?

A

trimethoprim + sulfamethoxazole

81
Q

What type of antimalarial drugs are tetracycline/doxycycline/clindamycin?

A

blood schizonticides

82
Q

What do antibiotics as antimalarial drugs target?

A

target components of the apicoplast (plant-like organelle that carries out many biochemical processes)

83
Q

What is doxycycline commonly paired with?

A

Commonly paired with quinine or quinidine for treatment of falciparum malaria

Pharmacology Test #2 (13 decks)

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