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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
5 drugs for prevention of clinical disease
Malarone (atovaquone + proguanil) Doxycycline Chloroquine Mefloquine Primaquine
26
Malarone area and preventive course
All areas start 1-2 days before, continue one week after
27
Doxy area and preventive course of treatment
All areas start 1-2 days before, continue 4 weeks after
28
Chloroquine areas and preventive course
Chloroquine sensitive areas start 1-2 weeks before and continue 4 weeks after
29
Mefloquine area and Pretreatment course
Mef-sensitive areas start more than two weeks before, continue more than four weeks after
30
Primaquine area and course of pretreatment
If \>90 P. vivax in the area Start 1-2 days before, continue one week after
31
Uncomplicated malaria (or unidentified species) can be treated with _____ agents Examples? (area-based)
**Oral** _Chloroquine sensitive areas:_ * chloroquine and hydroxychloroquine sulfate _Chloroquine resistant areas:_ * Malarone * Coartem (artemether + Lumefantrine) * Quinine Sulfate PLUS Doxy/Tetra//Clinda * Mefloquine
32
Treatment for uncomplicated malaria?
_P. vivax/ovale_ (hypnozoites in liver) \*\*Basically add **primaquine** to any of the treatments of uncomplicated malaria _P. malariae or Knowlesi_ **Chloroquine** or **Hydroxychloroquine**
33
Tx for severe/complicated malaria
Quinidine gluconate (I.V.) PLUS Doxy/Tetracycline/Clinda Cardio consult!
34
Alternative Tx for Severe/complicated malaria
**Artesunate** (= IV only alternative if QG not available or tolerated) Followed by one of: * **Malarone** * **Doxy** (**Clinda** in pregnant women) * **Mefloquone**
35
Artemisinin type
Sesquiterpene lactone endoperoxide (endoperoxide is the active group)
36
Artemisinin has low ___ but high \_\_\_\_
Low toxicity High counterfeit rate
37
Artemisinin resistance has been observed in \_\_\_\_\_
SE Asia
38
Artemisinin MOA
Must be **activated** (via heme-iron) Activated artemisinin forms **free radicals** that target parasite proteins/lipids
39
Artemisinin Mechanism of Resistance
Mutations in **Kelch 13 gene** --\>Delays life cycle, alters stress response
40
Artemisinin has no effect on ___ stage
Liver
41
Artemisinin half life
1-2 hours
42
Artemisinin is commonly paired with ______ and \_\_\_\_\_\_
Mefloquone or Lumefantrine
43
Artemisinin is ______ because of the required frequency of dosing
not appropriate for chemoprophylaxis
44
Artemisinin ROA It is also _____ with a low \_\_\_\_\_\_
Oral only insoluble with a low bioavailability
45
Semisynthetic artemisinins are available that allow...
different ROA's | (oral, IV, IM, rectal)
46
What is artesunate, what is the ROA, what does it treat?
Semisynthetic artemisinin IM, IV, rectal Treatment of severe malaria
47
Artemisinin antimalarial effect is associated with \_\_\_
C-max
48
Artemisinin derivatives are paired with \_\_\_\_\_
Longer half life drugs
49
3 Common combos for artemisinin
Amodiaquine mefloquine piperaquine
50
Artemisinin combos are standard of care for \_\_\_\_\_\_\_
uncomplicated falciparum in most areas
51
Artemisinin adverse effects
N/V/D Dizziness EMBRYOTOXIC in animal studies (not recommended for first trimester for uncomplicated malaria)
52
Malaria parasites ingest ____ from host cell This is degraded into ___ and \_\_\_\_\_, which is toxic Parasite also polymerizes it to \_\_\_\_\_,which is nontoxic
Hb amino acids and heme hemozoin
53
Chloroquine accumulates in _____ and inhibits \_\_\_\_\_\_\_
food vacuole inhibits heme polymerization
54
Antimalarials generally inhibit \_\_\_\_\_\_\_\_\_
The detoxification of heme
55
4-substituted quinolines interfere with \_\_\_\_\_\_\_\_\_\_ Resistance is associated with lack of \_\_\_\_\_\_\_\_\_
Heme polymerization Lack of accumulation in food vacuole
56
Hemozoin + Heme/quinoline complex --\>
Capped polymer
57
Chloroquine * ROA? * Has a large\_\_\_\_\_ * Initial/Terminal half-life?
Oral Large _volume of distribution_ Initial = 3-5d Terminal = 1-2d
58
Chloriquine (CQ) antimalarial effect is associated with...
T\>MIC
59
CQ might cause ____ in pts of african descent It is contraindicated for which 4 conditions?
_prutitis_ 1. psoriasis 2. porphyria 3. Retina/Visual field abnormalities 4. Myopathy
60
\_\_\_\_\_ and ____ interfere with the absorption of CQ
Kaolin and antacids
61
Two possible mechanisms of CQ resistance
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
Quinine isolated from \_\_\_\_\_\_\_
bark of cinchona tree
63
Mechanism of Quinine is similar to \_\_\_\_\_
Chloroquine
64
Quinine's general catergory
Blood schizontiide
65
Quinine is the treatment of choice for...
* **Chloroquine resistant falciparum** (quinine sulfate- oral) * **Severe falciparum** (IV only with concurrent cardiac monitoring)
66
Quinine dosing schedule for chemoprophylaxis?
N/A Its short half life and higher toxicity make it an inappropriate option for chemoprophylaxis.
67
Quinine major adverse effect
**Cinchonism** (tinnitus, headache, nauses, dizziness, flushing, visual disturb.)
68
Quinine may result in cell \_\_\_\_\_. Cause and Effects of this?
**_Cell hemolysis_** - G6PD deficiency - Blackwater fevere (hemoglobinuria)
69
Quinine DDI
May raise _warfarin_ and _digoxin_ levels **Metabolized by CYP3A4** \*\*\* Severe HoTN\*\*\*
70
Mefloquine effective against... What's its use?
Effective against **erythrocytic forms** of *falciparum* and *vivax* (Used for both prophylaxis and Rx)
71
Major Mefloquine side
Neuropsychiatric toxicity
72
Other chloroquine drugs
Lumefantrine Piperaquine Amodiaquine Halofantrine
73
Primaquine metabolism
2D6 metabolism Required for activity
74
Primaquine mechanism may involve \_\_\_\_
Free radicals
75
Primaquine is the drug of choice for \_\_\_\_\_\_\_
_Liver stages_ (*ACTIVELY GROWING* and *HYPNOZOITES*) Of **Vivax** and **Ovale** \*\*\* Combo with Chloroquine
76
Primaquine is a _______ drug against \_\_\_\_\_\_
gametocidal all four parasites
77
Contraindications for Primaquine
G6PD deficiency Pregnancy/Breastfeeding
78
What compound has the same spectrum of activity and toxicity as Primaquine
Tafenoquine
79
Malarone is a combo of \_\_\_\_\_\_
proguanil and atavaquone (atavaquone bad at monotherapy)
80
Malarone kills ______ stages, but not \_\_\_\_\_\_
liver and blood NOT hypnozoites
81
Malarone is effective Tx for \_\_\_\_\_\_\_\_\_\_
uncomplicated malaria and chemoprophylaxis
82
Atavaquone is used to treat \_\_\_\_\_\_\_\_\_\_
Toxoplasma and P. jiroveci
83
Atavaquone is a _____ analog that is an inhibitor of \_\_\_\_\_\_
* **Ubiquitin** * Electron acceptor for paraste dihydroorotate dehydrogenase * **Cytochrome bc1**
84
Atavaquone works synergisyically with \_\_\_\_ How?
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
Antibiotics as antimalarial drugs? What do they target?
**Tetracycline/ Doxycycline/ Clindamycin** --\> Target **Apicoplast**
86
Doxy is paired with ___ or ____ for treatment of \_\_\_\_\_\_\_\_
Quinine/Quinidine Falciparum
87
Doxy is also used for...
chemoprophylaxis in areas with high mefloquone resistance
88
Third most common food borne illness
Toxo
89
Toxo life cycle? Transmission routes?
* -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
DIagnostic stages of toxo (2)
1. Serological diagnosis 2. Direct ID of parasite from peripheral blood, amniotic fluid, or tissue section
91
Severe toxoplasmosis common with what diseases?
HIV/AIDS Transplants Chemotherapy
92
Congenital toxo occurs when?
First infection in mom
93
Drug treatment for toxo
First line = **Pyrimethamine** + **Sulfadiazine** Alternatives: atavaquone or pentamidine

Pharm Exam 2 (12 decks)

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