2: Antiparasitics - Not Malaria Flashcards
definitive host of toxoplasma gondii
cat
transmission of toxoplasma gondii
eating raw meat or cat feces
what is the 3rd most common food-borne illness?
toxoplasma gondii
describe the life cycle of T. gondii?
- sexual development only in cat!
- cysts develop in other mammals
who does toxoplasmosis usually effect?
- NOT people with functioning immune systems
- severe toxoplasmosis seen in : HIV, organ transplants, chemotherapy
how do babies get congenital toxoplasmosis?
fetus becomes infected via placenta in women who are infected for the first time
what is first line treatment for toxoplasmosis? alternate?
primethamine + sulfadiazine
alternate: atavaquone or pentamidine
what parasitic infections are associated with HIV in the US?
- pneumocystis jirovecii (pneumonia)
- toxoplasma gondii (encephalitis)
- cryptosporidium (cryptosporidiosis)
what parasitic infections are associated with HIV globally?
- malaria
- leishmania
- trypanosoma cruzi (Chagas disease)
structure of pentamidine
aromatic diamidine
administration of pentamidine and mechanism
- parenteral
- mechanism unknown, but preferentially accumulates in parasites
how toxic is pentamidine?
very - 50% of patients show side effects
-can cause hypoglycemia or hyperglycemia
what is pentamidine first line use for? what is an alternate treatment for?
first line: West African trypanosomiasis
alternate: visceral leishmania and pneumocystosis
what are 3 anaerobic protozoa that cause disease?
- entamoeba histolytica (amebiasis)
- giardia lamblia (giardiasis)
- trichomonas vaginalis
what is one of the most common water-borne diseases in the US?
giardia lamblia
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
what does entamoeba histolytica infection cause?
diarrhea + ulcers on the intestinal lining
how can one kill entamoeba cysts?
boiling, but NOT chlorination
what promotes the spread of amebiasis?
poor sanitation and fecal contamination of food and water
where is amebiasis more common?
Latin America, Africa, and Indian subcontinent
where does amebiasis initially infect?
intestine - sometimes reaches other organs, such as liver
symptoms of amebiasis
most asymptomatic, but if present:
- diarrhea
- increased flatulence
- abdominal cramps
- sometimes liver abscesses
symptoms of giardiasis
range from asymptomatic to severe diarrhea and malabsorption
treatments of choice for giardiasis
- metronidazole
- nitazoxanide
what is the most frequent cause of recreational water-related disease outbreaks?
cryptosporidium
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
drug of choice for cryptosporidium
nitazoxanide
where does trichomonas reside in males and females?
males: urethra and prostate
females: lower genital tract
how does trichomonas present in both genders?
males: often asymptomatic
females:
- vaginitis + purulent discharge
- vulvar and cervical lesions
- abdominal pain
- dysuria
- dyspareunia
what is metronidazole the drug of choice for? what does it kill?
- extraintestinal Entamoeba histolytica
- giardiasis
- trichomoniasis
kills trophozoites but not cysts
what is metronidazole treatment usually followed by and why?
luminal drug to eliminate asymptomatic infection
what is the mechanism of action of metronidazole
not definitively known - anaerobes have electron transport proteins with low redox potential - activate metronidazole
what is a drug similar to metronidazole? how does it differ slightly?
tinidazole - less toxicity
describe metronidazole + alcohol effects
may cause an antabuse effect (similar to disulfram + alcohol) -nausea, vomit, increased HR
-inhibits acetaldehyde DH -> accumulate acetaldehyde
drugs for intestinal forms of amebiasis
- paromomycin
- iodoquinol
what type of drug is paromomycin?
aminoglycoside
-not significantly absorbed in GI tract
effectiveness and other use for paromomycin
similar efficacy and less toxic than other drugs
also active against cryptosporidium
what is iodoquinol commonly used in combo with?
metronidazole
mechanism of iodoquinol
unknown
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
what is nitazoxanide effective against?
inhibits growth of sporozoites and oocysts of cryptosporidium parvum and trophozoites of giardia
what are the kinetoplastid parasites?
- leishmania
- african trypanosomes (brucei gambiense, brucei rhodesiense)
- american trypanosomes (cruzi)
what types of infection does leishmania cause?
skin, mucocutaneous, organ
what do african trypanosomes cause?
african sleeping sickness (95% gambiense)
what do american trypanosomes cause?
Chagas disease
what common features do kinetoplastid parasites share?
- unique organelles: kinetoplast, glycosome
- distinct mechanisms of gene expression
anti-kinetoplastid drugs for leishmaniasis
- sodium stibogluconate or Ampho B
- alternatives: pentamidine or MILTEFOSINE
anti-kinetoplastid drugs for african trypanosomiasis
- early stage: pentamidine (west) or suramin (east)
- late stage: melarsoprol (east and west) or eflornithine (west)
anti-kinetoplastid drugs for american trypanosomiasis
-nifurtimox or benznidazole
what type of drug is miltefosine?
phospholipid analog
- developed as an anticancer drug
- approved for use against visceral leishmaniasis (India)
miltefosine: mechanism, resistance, side effects, contraindications?
unknown - resistance has been observed, side effects tolerable
*don’t use in preggers: teratogenic!
how many daily doses of miltefosine yields cure rates ~100%?
28 daily doses
MOA of nifurtimox and benznidazole
unknown - activated by an NADH-dependent mitochondrial nitroreductase -> generation of nitro radical anions
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
how are nifurtimox and benznidazole administered?
- p.o.
- 3-4 month course
toxicity of nifurtimox and benznidazole
common - hypersensitivity, GI complications -> leads to premature stoppage of treatment
