2: Antiparasitics - Not Malaria Flashcards Preview

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Flashcards in 2: Antiparasitics - Not Malaria Deck (56):
1

definitive host of toxoplasma gondii

cat

2

transmission of toxoplasma gondii

eating raw meat or cat feces

3

what is the 3rd most common food-borne illness?

toxoplasma gondii

4

describe the life cycle of T. gondii?

-sexual development only in cat!
-cysts develop in other mammals

5

who does toxoplasmosis usually effect?

-NOT people with functioning immune systems
-severe toxoplasmosis seen in : HIV, organ transplants, chemotherapy

6

how do babies get congenital toxoplasmosis?

fetus becomes infected via placenta in women who are infected for the first time

7

what is first line treatment for toxoplasmosis? alternate?

primethamine + sulfadiazine

alternate: atavaquone or pentamidine

8

what parasitic infections are associated with HIV in the US?

-pneumocystis jirovecii (pneumonia)
-toxoplasma gondii (encephalitis)
-cryptosporidium (cryptosporidiosis)

9

what parasitic infections are associated with HIV globally?

-malaria
-leishmania
-trypanosoma cruzi (Chagas disease)

10

structure of pentamidine

aromatic diamidine

11

administration of pentamidine and mechanism

-parenteral
-mechanism unknown, but preferentially accumulates in parasites

12

how toxic is pentamidine?

very - 50% of patients show side effects
-can cause hypoglycemia or hyperglycemia

13

what is pentamidine first line use for? what is an alternate treatment for?

first line: West African trypanosomiasis
alternate: visceral leishmania and pneumocystosis

14

what are 3 anaerobic protozoa that cause disease?

-entamoeba histolytica (amebiasis)
-giardia lamblia (giardiasis)
-trichomonas vaginalis

15

what is one of the most common water-borne diseases in the US?

giardia lamblia

16

describe entamoeba histolytica infection process

ingest cysts -> forms trophozoites in ileum -> penetrates intestinal wall -> multiplication of trophozoites w/i colon wall -> systemic invasion

some cysts (infective) and trophozoites (non-infective) pass with feces

17

what does entamoeba histolytica infection cause?

diarrhea + ulcers on the intestinal lining

18

how can one kill entamoeba cysts?

boiling, but NOT chlorination

19

what promotes the spread of amebiasis?

poor sanitation and fecal contamination of food and water

20

where is amebiasis more common?

Latin America, Africa, and Indian subcontinent

21

where does amebiasis initially infect?

intestine - sometimes reaches other organs, such as liver

22

symptoms of amebiasis

most asymptomatic, but if present:
-diarrhea
-increased flatulence
-abdominal cramps
-sometimes liver abscesses

23

symptoms of giardiasis

range from asymptomatic to severe diarrhea and malabsorption

24

treatments of choice for giardiasis

-metronidazole
-nitazoxanide

25

what is the most frequent cause of recreational water-related disease outbreaks?

cryptosporidium

26

what is the most common symptom of cryptosporidium? what are other symptoms?

watery diarrhea***
-stomach cramps/pain
-dehydration
-nausea/vomit
-fever
-weight loss
-more serious illness in immunocompromised people

27

drug of choice for cryptosporidium

nitazoxanide

28

where does trichomonas reside in males and females?

males: urethra and prostate
females: lower genital tract

29

how does trichomonas present in both genders?

males: often asymptomatic

females:
-vaginitis + purulent discharge
-vulvar and cervical lesions
-abdominal pain
-dysuria
-dyspareunia

30

what is metronidazole the drug of choice for? what does it kill?

-extraintestinal Entamoeba histolytica
-giardiasis
-trichomoniasis

kills trophozoites but not cysts

31

what is metronidazole treatment usually followed by and why?

luminal drug to eliminate asymptomatic infection

32

what is the mechanism of action of metronidazole

not definitively known - anaerobes have electron transport proteins with low redox potential - activate metronidazole

33

what is a drug similar to metronidazole? how does it differ slightly?

tinidazole - less toxicity

34

describe metronidazole + alcohol effects

may cause an antabuse effect (similar to disulfram + alcohol) -nausea, vomit, increased HR
-inhibits acetaldehyde DH -> accumulate acetaldehyde

35

drugs for intestinal forms of amebiasis

-paromomycin
-iodoquinol

36

what type of drug is paromomycin?

aminoglycoside
-not significantly absorbed in GI tract

37

effectiveness and other use for paromomycin

similar efficacy and less toxic than other drugs

also active against cryptosporidium

38

what is iodoquinol commonly used in combo with?

metronidazole

39

mechanism of iodoquinol

unknown

40

mechanism of action of nitazoxanide

prodrug - rapidly turned into active tizoxanide

mechaism uncertain:
-interferes with pyruvate:ferredoxin (PFOR) enzyme-dependent electron transfer rxn
-inhibits anaerobic metabolism

41

what is nitazoxanide effective against?

inhibits growth of sporozoites and oocysts of cryptosporidium parvum and trophozoites of giardia

42

what are the kinetoplastid parasites?

-leishmania
-african trypanosomes (brucei gambiense, brucei rhodesiense)
-american trypanosomes (cruzi)

43

what types of infection does leishmania cause?

skin, mucocutaneous, organ

44

what do african trypanosomes cause?

african sleeping sickness (95% gambiense)

45

what do american trypanosomes cause?

Chagas disease

46

what common features do kinetoplastid parasites share?

-unique organelles: kinetoplast, glycosome
-distinct mechanisms of gene expression

47

anti-kinetoplastid drugs for leishmaniasis

-sodium stibogluconate or Ampho B
-alternatives: pentamidine or MILTEFOSINE

48

anti-kinetoplastid drugs for african trypanosomiasis

-early stage: pentamidine (west) or suramin (east)
-late stage: melarsoprol (east and west) or eflornithine (west)

49

anti-kinetoplastid drugs for american trypanosomiasis

-nifurtimox or benznidazole

50

what type of drug is miltefosine?

phospholipid analog
-developed as an anticancer drug
-approved for use against visceral leishmaniasis (India)

51

miltefosine: mechanism, resistance, side effects, contraindications?

unknown - resistance has been observed, side effects tolerable
*don't use in preggers: teratogenic!

52

how many daily doses of miltefosine yields cure rates ~100%?

28 daily doses

53

MOA of nifurtimox and benznidazole

unknown - activated by an NADH-dependent mitochondrial nitroreductase -> generation of nitro radical anions

54

how much do nifurtimox and benznidazole reduce severity in acute phase?

eliminates parasite in 80% of acute infections and ~50% of chronic infections, but does not reverse tissue damage in chronic infections

55

how are nifurtimox and benznidazole administered?

-p.o.
-3-4 month course

56

toxicity of nifurtimox and benznidazole

common - hypersensitivity, GI complications -> leads to premature stoppage of treatment