hemolytic anemia, malaria, G6PD, and pharm - Stillwell/Lee Flashcards

1
Q

malaria

A
  • single cell protozoa
  • deaths usually due to P. falciparum –> stick to endothelial cells obstructing microcirculation (ex. cerebral malaria)**
  • anopheles mosquito
  • P. vivax in US
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2
Q

malaria life cycle

A
  • sporozoite (mosquito saliva) –> exoerythrocytic form in liver (schizonts –> merozoites) –> erythrocytic phase (merozoites –> trophozoites –> schizonts –> merozoites)
  • vivax and oval can live dormant in liver (hypnozoite)** –> high risk of reinfection
  • merozoites can infect gametocytes (taken up by mosquitos)
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3
Q

which forms banana gametocytes?

A

P. falciparum

-all of them have ring forms

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4
Q

malaria signs/symptoms

A
  • paroxysms = cyclic fevers, chills, sweats (from schizont rupture and cytokine response)
  • vivax and ovale –> tertian fever (2 days)**; can also lie dormant for months
  • malariae –> quartan fever (3 days)**
  • falciparum –> irregular fevers; no dormancy
  • sever infection –> hemolytic anemia (from parasite) and blackwater fever (bilirubin, Hb, and renal failure)**
  • blackwater only from P. falciparum*
  • other sever symptoms with P. falciparum –> pulmonary edema, cerebral malaria, stillbirth, miscarriage
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5
Q

malaria protection

A
  • sickle cell disease trait (HbS trait)**
  • Hb C, E trait
  • G6PD deficiency
  • thalassemia
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6
Q

malaria diagnosis

A
  • thick/thin blood smears on Wright/Giemsa stain**
  • thick more sensitive (identify parasites), thin for speciation
  • smears every 12-24 hr 3x**
  • only do PCRs 1x
  • serology antibodies take a long time to turn +
  • ringforms on thin smear**
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7
Q

P. falciparum on smears

A
  • banana gametocyte and high parasitemia (lot of RBCs infected)
  • may have >60% parasitemia
  • transfusions with >10% parasitemia
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8
Q

malaria treatment and prophylaxis

A

-slide 22,23

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9
Q

malaria treatment

A
  • artemisinins and combined coartem –> for very sick people; obtained through CDC
  • malarone –> for mild-moderate malaria in US (GI side effects)**
  • mefloquine –> CNS side effects**
  • chloroquine –> for malaria in Central America, haiti, Dominican, and Middle East (everywhere else is resistant)**
  • quinine –> toxicity called cinchoism (tinnitus, nausea, headaches, dizziness, hemolytic anemia)
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10
Q

terminal therapy for malaria**

A
  • used to eliminate dormant hypnozoites of ovale/vivax in liver to prevent relapse**
  • give primaquine (daily for 2 weeks) or tafenoquine (1x)**
  • these drugs can cause hemolytic anemia with G6PDH deficiency**
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11
Q

babesia

A
  • can mimic malaria; parasite
  • cause hemolytic anemia
  • ring forms - Maltese cross**
  • spread by ticks
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12
Q

bartonella bacilliformis

A
  • cause hemolytic anemia; bacteria
  • spread by sandflies** –> Oroya fever/Carrion’s disease**
  • look like spikes
  • hemolytic phase –> skin lesion phase (verruga peruana)**
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13
Q

toxoplasma gondii

A
  • cause hemolytic anemia; parasite

- undercooked meat and cat feces**

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14
Q

liver stage drugs

A
  1. atovaquone-proguanil (malarone)

2. primaquine

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15
Q

blood stage drugs

A
  1. artemether + Lumefantrine (Coartem) - an artemisinin
  2. antifolates
  3. quinolones (chloroquine, quinine, mefloquine)
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16
Q

gametocyte drugs

A
  1. primaquine

2. coartem - artemisinin

17
Q

interferes with heme polymerization?

A

quinolones –> prevent sequestering of heme in hemosome –> toxicity to malaria**

  1. chloroquine
  2. quinine
  3. mefloquine
18
Q

disrupt electron transport chain?

A
  1. atovaquone
19
Q

inhibit folate synthesis?

A

antifolates

  1. sulfadoxine
  2. pyrimethamine
20
Q

inhibit protein synthesis?

A

antimicrobials

  1. clindamycin
  2. doxycycline
  3. tetracycline
21
Q

production of free radicals?

A

oxidative stress

1. artemether + lumefantrine (coartem) - an artemisinin

22
Q

chloroquine

A
  • against erythrocytic form**
  • action: in food vacuoles and inhibits heme polymerization (hemozoin) –> heme toxicity to malaria**
  • indications: effective against non-falciparum and sensitive falciparum**
  • resistance high for falciparum (maybe vivax)**
  • contraindications: psoriasis, porphyria, retinal deficits, myopathy
  • not effective in exoerythrocytic forms –> relapse of vivax and ovale (even malariae)**
23
Q

primaquine

A
  • hydroxylated metabolites form free radicals and reactive oxygen species** –> oxidative stress
  • effective against liver forms (hypnozoites from ovale/vivax) and gametocytes; not erythrocytic form**
  • prevents relapse
  • combined with chloroquine for erythrocyte form
  • contraindications/side effects: pregnancy (G6PD deficiency)** –> can form malaria if deficient**; also rheumatoid arthritis or lupus
24
Q

G6PD

A
  • enzyme used to make NADPH for GSH to remove oxidative stress
  • X linked deficiency –> can’t remove oxidative stress
  • see Heinz bodies and bite cells
25
Q

tafenoquone

A
  • derivative of primaquine but 2x longer half life
  • adverse effects if G6PD deficient
  • give one dose
26
Q

atovaquone-proguanil (malarone)

A
  • effective against both erythrocytic and hepatic forms of malaria
  • atovaquone –> disrupts electron transport chain, rifampin reduces levels*
  • proguanil –> inhibitor of dihydrofolate reductase thymidylate synthase (enhance mitochondrial toxicity), GI side effects
  • both effective against falciparum in combination
27
Q

mefloquine

A
  • only effects erythrocytic form –> against schizont activity**
  • effect heme polymerization
  • drug of choice for chloroquine resistant malaria**
  • contraindications/adverse effects: epilepsy, psychiatric disorder, GI, seizures, psychosis
28
Q

quinine and quinidine

A
  • affects the erythrocyte form
  • heme polymerization to prevent detoxification –> toxic to malaria
  • no effect on sporozoites or hepatic forms**
  • 1st line of defense for falciparum malaria (especially severe disease)**
  • standard for parenteral treatment**
  • contraindications: sever cinchonism (tinnitus, headache, nausea), hemolysis, hypersensitivity, renal problems
  • adverse effects: cinchonism, cardiac arrhythmia, antimuscarinic
  • avoid mefloquine
  • can raise plasma levels of warfarin and digoxin**
29
Q

artemisinin

A
  • only erythrocytic forms

- get from CDC

30
Q

artemether-lumefantrine

A
  • an artemisinin
  • inhibit nucleic acid and protein synthesis** (prophylaxis does not always work)
  • treat severe P. falciparum**
  • adverse effects: teratogen in animals
31
Q

pyrimethamine

A
  • only against erythrocytic forms
  • inhibit DHFR (folate pathway)**
  • combined with sulfdoxin (inhibits DHPS in folate path)**
  • both inhibit folate –> no DNA –> cell death
  • against erythrocytic forms of ALL 4 P. malaria species**
  • contraindications: not given to someone who is folate deficient (ex. pregnancy)
  • adverse effects: GI, skin rashes (ex. SJS, TEN)
  • falciparum sometimes resistant to folate antagonists and sulfonamides