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Pharm > 2: Antiparasitics - Not Malaria > Flashcards

2: Antiparasitics - Not Malaria Flashcards

1
Q

definitive host of toxoplasma gondii

A

cat

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2
Q

transmission of toxoplasma gondii

A

eating raw meat or cat feces

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3
Q

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

A

toxoplasma gondii

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4
Q

describe the life cycle of T. gondii?

A
  • sexual development only in cat!

- cysts develop in other mammals

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5
Q

who does toxoplasmosis usually effect?

A
  • NOT people with functioning immune systems

- severe toxoplasmosis seen in : HIV, organ transplants, chemotherapy

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6
Q

how do babies get congenital toxoplasmosis?

A

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

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7
Q

what is first line treatment for toxoplasmosis? alternate?

A

primethamine + sulfadiazine

alternate: atavaquone or pentamidine

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8
Q

what parasitic infections are associated with HIV in the US?

A
  • pneumocystis jirovecii (pneumonia)
  • toxoplasma gondii (encephalitis)
  • cryptosporidium (cryptosporidiosis)
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9
Q

what parasitic infections are associated with HIV globally?

A
  • malaria
  • leishmania
  • trypanosoma cruzi (Chagas disease)
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10
Q

structure of pentamidine

A

aromatic diamidine

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11
Q

administration of pentamidine and mechanism

A
  • parenteral

- mechanism unknown, but preferentially accumulates in parasites

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12
Q

how toxic is pentamidine?

A

very - 50% of patients show side effects

-can cause hypoglycemia or hyperglycemia

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13
Q

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

A

first line: West African trypanosomiasis

alternate: visceral leishmania and pneumocystosis

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14
Q

what are 3 anaerobic protozoa that cause disease?

A
  • entamoeba histolytica (amebiasis)
  • giardia lamblia (giardiasis)
  • trichomonas vaginalis
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15
Q

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

A

giardia lamblia

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16
Q

describe entamoeba histolytica infection process

A

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

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17
Q

what does entamoeba histolytica infection cause?

A

diarrhea + ulcers on the intestinal lining

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18
Q

how can one kill entamoeba cysts?

A

boiling, but NOT chlorination

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19
Q

what promotes the spread of amebiasis?

A

poor sanitation and fecal contamination of food and water

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20
Q

where is amebiasis more common?

A

Latin America, Africa, and Indian subcontinent

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21
Q

where does amebiasis initially infect?

A

intestine - sometimes reaches other organs, such as liver

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22
Q

symptoms of amebiasis

A

most asymptomatic, but if present:

  • diarrhea
  • increased flatulence
  • abdominal cramps
  • sometimes liver abscesses
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23
Q

symptoms of giardiasis

A

range from asymptomatic to severe diarrhea and malabsorption

24
Q

treatments of choice for giardiasis

A
  • metronidazole

- nitazoxanide

25
Q

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

A

cryptosporidium

26
Q

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

A

watery diarrhea***

  • stomach cramps/pain
  • dehydration
  • nausea/vomit
  • fever
  • weight loss
  • more serious illness in immunocompromised people
27
Q

drug of choice for cryptosporidium

A

nitazoxanide

28
Q

where does trichomonas reside in males and females?

A

males: urethra and prostate
females: lower genital tract

29
Q

how does trichomonas present in both genders?

A

males: often asymptomatic

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

30
Q

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

A
  • extraintestinal Entamoeba histolytica
  • giardiasis
  • trichomoniasis

kills trophozoites but not cysts

31
Q

what is metronidazole treatment usually followed by and why?

A

luminal drug to eliminate asymptomatic infection

32
Q

what is the mechanism of action of metronidazole

A

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

33
Q

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

A

tinidazole - less toxicity

34
Q

describe metronidazole + alcohol effects

A

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

35
Q

drugs for intestinal forms of amebiasis

A
  • paromomycin

- iodoquinol

36
Q

what type of drug is paromomycin?

A

aminoglycoside

-not significantly absorbed in GI tract

37
Q

effectiveness and other use for paromomycin

A

similar efficacy and less toxic than other drugs

also active against cryptosporidium

38
Q

what is iodoquinol commonly used in combo with?

A

metronidazole

39
Q

mechanism of iodoquinol

A

unknown

40
Q

mechanism of action of nitazoxanide

A

prodrug - rapidly turned into active tizoxanide

mechaism uncertain:

  • interferes with pyruvate:ferredoxin (PFOR) enzyme-dependent electron transfer rxn
  • inhibits anaerobic metabolism
41
Q

what is nitazoxanide effective against?

A

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

42
Q

what are the kinetoplastid parasites?

A
  • leishmania
  • african trypanosomes (brucei gambiense, brucei rhodesiense)
  • american trypanosomes (cruzi)
43
Q

what types of infection does leishmania cause?

A

skin, mucocutaneous, organ

44
Q

what do african trypanosomes cause?

A

african sleeping sickness (95% gambiense)

45
Q

what do american trypanosomes cause?

A

Chagas disease

46
Q

what common features do kinetoplastid parasites share?

A
  • unique organelles: kinetoplast, glycosome

- distinct mechanisms of gene expression

47
Q

anti-kinetoplastid drugs for leishmaniasis

A
  • sodium stibogluconate or Ampho B

- alternatives: pentamidine or MILTEFOSINE

48
Q

anti-kinetoplastid drugs for african trypanosomiasis

A
  • early stage: pentamidine (west) or suramin (east)

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

49
Q

anti-kinetoplastid drugs for american trypanosomiasis

A

-nifurtimox or benznidazole

50
Q

what type of drug is miltefosine?

A

phospholipid analog

  • developed as an anticancer drug
  • approved for use against visceral leishmaniasis (India)
51
Q

miltefosine: mechanism, resistance, side effects, contraindications?

A

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

52
Q

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

A

28 daily doses

53
Q

MOA of nifurtimox and benznidazole

A

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

54
Q

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

A

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

55
Q

how are nifurtimox and benznidazole administered?

A
  • p.o.

- 3-4 month course

56
Q

toxicity of nifurtimox and benznidazole

A

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

Pharm (19 decks)

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