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Pharm Exam 2 > Malaria (and Toxo) > Flashcards

Malaria (and Toxo) Flashcards

1
Q

The one exception to the “No vaccines” claim that was given in class

A

RTSS vaccine for malaria

(50% reduction in cases)

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2
Q

Malaria is caused by the genus ______

A

Plasmodium

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3
Q

Most severe Plasmodium?

Common in ____

A

falciparum

common in tropics

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4
Q

Less common plasmodium species?

Why is it less common?

Where is it found?

A

Vivax

Infection is limited to reticulocytes

Common in subtropics and temerate regions

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5
Q

Third and fourth common plasmodiums?

What are the types of infections they cause?

A

Ovale = Relapsing malaria

knowlesi = 24 hour life cycle, zoonotic infections

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6
Q

Where is plasmodium ovale found?

A

West africa

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7
Q

What is the fastest-replicating plasmodium species?

A

Knowlesi

It has a 24 hour lifecycle, which means it can increase the population very quickly

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8
Q

Plasmodium Life cycle:

  1. Infected mosquito injects____
  2. They go to the liver and become _____
  3. They are released and invade ___ cells
  4. Once in the cell, these become ______
  5. This multiplies, giving more ______
  6. These are released and become _____
  7. Female mosquito picks them up and _____ are formed
A
  1. Sporozoites
  2. Merozoites
  3. Red blood cells
  4. Trophozoites
  5. New merozoites
  6. gametocytes
  7. sporozoites
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9
Q

Which plasmodium forms hypnozoites?

How/where does this form live?

How do you treat for this?

A

Vivax

Lies dormant in the liver

It only responds to Primaquine

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10
Q

How does plasmodium bind to the placenta?

A

It binds to chondroitin sulfate A

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11
Q

Three conditions covered in malaria pathogenesis

A

Cerebral malaria

Severe anemia

Metabolic acidosis

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12
Q

Cerebral malaria pathogenesis

A

Blood brain barrier disruption (from ROS) = Edema and hemorrhage

Tissue hypoxia (from Microvascular obstruction) = Parenchymal and axonal damage

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13
Q

What causes severe anemia in malaria pathogenesis

A

Hemolysis of immature RBCs

(Rosetting)

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14
Q

What causes the metabolic acidosis in malaria?

A

Tissue hypoxia causes lactic acid from anaerobic glycolysis

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15
Q

Three stages of classic, uncomplicated malaria

A

Cold stage

hot stage

sweating stage

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16
Q

The symptoms of uncomplicated malaria are generally _______

A

Flu-like

(Chills, headache, myalgias and malaise)

also ANEMIA and JAUNDICE

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17
Q

5 major symptoms of severe malaria

A

Organ failures (renal)

Cerebral malaria

Anemia

Hemoglobinuria

Acute respiratory distress syndrome

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18
Q

What is malaria during pregnancy called?

Features?

A

Placental Malaria

Especially during first pregnancy, causes low birth weight and miscarriage

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19
Q

Antimalarials, three categories and what they target:

A

Tissue schizonticides = kill liver stage

Blood schizonticides = kill erythrocytic forms

Gametocytocides = kill sexual stages and block transmission

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20
Q

All antimalarial compounds are effective against ______

A

Asexual blood stages

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21
Q

Antimalarials that target Liver stage

A

Artemisinins

Primaquine

Pyrimethamine

Atovaquone

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22
Q

Antimalarials that target the hypnozoites

A

Primaquine

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23
Q

Antimalarials that target gametocytes

A

Artemisinins

Mefloquine

Amodiaquine

Primaquine

Pyrimethamine

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24
Q

Four methods of malaria prevention

A

Insect repellent

Insecticides

Bed nets

Chemoprophylaxis

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25
Q

5 drugs for prevention of clinical disease

A

Malarone (atovaquone + proguanil)

Doxycycline

Chloroquine

Mefloquine

Primaquine

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26
Q

Malarone area and preventive course

A

All areas

start 1-2 days before, continue one week after

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27
Q

Doxy area and preventive course of treatment

A

All areas

start 1-2 days before, continue 4 weeks after

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28
Q

Chloroquine areas and preventive course

A

Chloroquine sensitive areas

start 1-2 weeks before and continue 4 weeks after

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29
Q

Mefloquine area and Pretreatment course

A

Mef-sensitive areas

start more than two weeks before, continue more than four weeks after

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30
Q

Primaquine area and course of pretreatment

A

If >90 P. vivax in the area

Start 1-2 days before, continue one week after

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31
Q

Uncomplicated malaria (or unidentified species) can be treated with _____ agents

Examples? (area-based)

A

Oral

Chloroquine sensitive areas:

  • chloroquine and hydroxychloroquine sulfate

Chloroquine resistant areas:

  • Malarone
  • Coartem (artemether + Lumefantrine)
  • Quinine Sulfate PLUS Doxy/Tetra//Clinda
  • Mefloquine
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32
Q

Treatment for uncomplicated malaria?

A

P. vivax/ovale (hypnozoites in liver)

**Basically add primaquine to any of the treatments of uncomplicated malaria

P. malariae or Knowlesi

Chloroquine or Hydroxychloroquine

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33
Q

Tx for severe/complicated malaria

A

Quinidine gluconate (I.V.) PLUS Doxy/Tetracycline/Clinda

Cardio consult!

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34
Q

Alternative Tx for Severe/complicated malaria

A

Artesunate (= IV only alternative if QG not available or tolerated)

Followed by one of:

  • Malarone
  • Doxy (Clinda in pregnant women)
  • Mefloquone
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35
Q

Artemisinin type

A

Sesquiterpene lactone endoperoxide

(endoperoxide is the active group)

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36
Q

Artemisinin has low ___ but high ____

A

Low toxicity

High counterfeit rate

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37
Q

Artemisinin resistance has been observed in _____

A

SE Asia

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38
Q

Artemisinin MOA

A

Must be activated (via heme-iron)

Activated artemisinin forms free radicals that target parasite proteins/lipids

39
Q

Artemisinin Mechanism of Resistance

A

Mutations in Kelch 13 gene

–>Delays life cycle, alters stress response

40
Q

Artemisinin has no effect on ___ stage

A

Liver

41
Q

Artemisinin half life

A

1-2 hours

42
Q

Artemisinin is commonly paired with ______ and ______

A

Mefloquone or Lumefantrine

43
Q

Artemisinin is ______ because of the required frequency of dosing

A

not appropriate for chemoprophylaxis

44
Q

Artemisinin ROA

It is also _____ with a low ______

A

Oral only

insoluble with a low bioavailability

45
Q

Semisynthetic artemisinins are available that allow…

A

different ROA’s

(oral, IV, IM, rectal)

46
Q

What is artesunate, what is the ROA, what does it treat?

A

Semisynthetic artemisinin

IM, IV, rectal

Treatment of severe malaria

47
Q

Artemisinin antimalarial effect is associated with ___

A

C-max

48
Q

Artemisinin derivatives are paired with _____

A

Longer half life drugs

49
Q

3 Common combos for artemisinin

A

Amodiaquine

mefloquine

piperaquine

50
Q

Artemisinin combos are standard of care for _______

A

uncomplicated falciparum in most areas

51
Q

Artemisinin adverse effects

A

N/V/D

Dizziness

EMBRYOTOXIC in animal studies (not recommended for first trimester for uncomplicated malaria)

52
Q

Malaria parasites ingest ____ from host cell

This is degraded into ___ and _____, which is toxic

Parasite also polymerizes it to _____,which is nontoxic

A

Hb

amino acids and heme

hemozoin

53
Q

Chloroquine accumulates in _____ and inhibits _______

A

food vacuole

inhibits heme polymerization

54
Q

Antimalarials generally inhibit _________

A

The detoxification of heme

55
Q

4-substituted quinolines interfere with __________

Resistance is associated with lack of _________

A

Heme polymerization

Lack of accumulation in food vacuole

56
Q

Hemozoin + Heme/quinoline complex –>

A

Capped polymer

57
Q

Chloroquine

  • ROA?
  • Has a large_____
  • Initial/Terminal half-life?
A

Oral

Large volume of distribution

Initial = 3-5d

Terminal = 1-2d

58
Q

Chloriquine (CQ) antimalarial effect is associated with…

A

T>MIC

59
Q

CQ might cause ____ in pts of african descent

It is contraindicated for which 4 conditions?

A

prutitis

  1. psoriasis
  2. porphyria
  3. Retina/Visual field abnormalities
  4. Myopathy
60
Q

_____ and ____ interfere with the absorption of CQ

A

Kaolin and antacids

61
Q

Two possible mechanisms of CQ resistance

A

Primary = mutation in Pf-CRT1

(localized to food vacuole, causes reduced accumulation of CQ, no cross resistance to mefloquine or quinine)

Secondary = over-expression of Pf-MDR1

(drug transporter)

62
Q

Quinine isolated from _______

A

bark of cinchona tree

63
Q

Mechanism of Quinine is similar to _____

A

Chloroquine

64
Q

Quinine’s general catergory

A

Blood schizontiide

65
Q

Quinine is the treatment of choice for…

A
  • Chloroquine resistant falciparum (quinine sulfate- oral)
  • Severe falciparum (IV only with concurrent cardiac monitoring)
66
Q

Quinine dosing schedule for chemoprophylaxis?

A

N/A

Its short half life and higher toxicity make it an inappropriate option for chemoprophylaxis.

67
Q

Quinine major adverse effect

A

Cinchonism

(tinnitus, headache, nauses, dizziness, flushing, visual disturb.)

68
Q

Quinine may result in cell _____. Cause and Effects of this?

A

Cell hemolysis

  • G6PD deficiency
  • Blackwater fevere (hemoglobinuria)
69
Q

Quinine DDI

A

May raise warfarin and digoxin levels

Metabolized by CYP3A4

*** Severe HoTN***

70
Q

Mefloquine effective against…

What’s its use?

A

Effective against erythrocytic forms of falciparum and vivax

(Used for both prophylaxis and Rx)

71
Q

Major Mefloquine side

A

Neuropsychiatric toxicity

72
Q

Other chloroquine drugs

A

Lumefantrine

Piperaquine

Amodiaquine

Halofantrine

73
Q

Primaquine metabolism

A

2D6 metabolism

Required for activity

74
Q

Primaquine mechanism may involve ____

A

Free radicals

75
Q

Primaquine is the drug of choice for _______

A

Liver stages (ACTIVELY GROWING and HYPNOZOITES)

Of Vivax and Ovale

*** Combo with Chloroquine

76
Q

Primaquine is a _______ drug against ______

A

gametocidal

all four parasites

77
Q

Contraindications for Primaquine

A

G6PD deficiency

Pregnancy/Breastfeeding

78
Q

What compound has the same spectrum of activity and toxicity as Primaquine

A

Tafenoquine

79
Q

Malarone is a combo of ______

A

proguanil and atavaquone

(atavaquone bad at monotherapy)

80
Q

Malarone kills ______ stages, but not ______

A

liver and blood

NOT hypnozoites

81
Q

Malarone is effective Tx for __________

A

uncomplicated malaria and chemoprophylaxis

82
Q

Atavaquone is used to treat __________

A

Toxoplasma and P. jiroveci

83
Q

Atavaquone is a _____ analog that is an inhibitor of ______

A
  • Ubiquitin
    • Electron acceptor for paraste dihydroorotate dehydrogenase
  • Cytochrome bc1
84
Q

Atavaquone works synergisyically with ____

How?

A

Proguanil

Proguanil is converter to cycloguanil = an inhibitor of plasmodium dihydrofolate reductase-thymidylate synthetase (crucial for purine and pyrim. synthesis)

–> Enhances mitochondrial toxicity of atavaquone

85
Q

Antibiotics as antimalarial drugs?

What do they target?

A

Tetracycline/ Doxycycline/ Clindamycin

–> Target Apicoplast

86
Q

Doxy is paired with ___ or ____ for treatment of ________

A

Quinine/Quinidine

Falciparum

87
Q

Doxy is also used for…

A

chemoprophylaxis in areas with high mefloquone resistance

88
Q

Third most common food borne illness

A

Toxo

89
Q

Toxo life cycle?

Transmission routes?

A
  • -sexual development in cat
  • -cysts develop in other mammals
    • Oocysts and tissue cysts –> tachyzoites –> neural/muscle –> Bradyzoites

Can be infected by eating raw meat (cysts) or from shedding from cats (oocysts)

90
Q

DIagnostic stages of toxo (2)

A
  1. Serological diagnosis
  2. Direct ID of parasite from peripheral blood, amniotic fluid, or tissue section
91
Q

Severe toxoplasmosis common with what diseases?

A

HIV/AIDS

Transplants

Chemotherapy

92
Q

Congenital toxo occurs when?

A

First infection in mom

93
Q

Drug treatment for toxo

A

First line = Pyrimethamine + Sulfadiazine

Alternatives: atavaquone or pentamidine

Pharm Exam 2 (12 decks)

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