anti-protazoan parasitic drugs Flashcards
what are some protazoal infections of the blood and tissue
plasmodium (malaria) babesia (babesiosis) leishmania (chronic ulcers/viceral) trypanosoma toxoplasma gondii
what are some protozoal infections of the intestines
etamoeba histolytica (liver abcess, dysentery) giardia lamblia (chronic diarrhea) cryptosporidium parvum (OI, diarrhea)
what are some urogenital protozoal infections
trichomaonas vaginalis (STD)
what are the key characteristics of plasmodium falciparum
can infect all RBCs
causes agglutination, blood gets stuck in microcirculation
sleeping form occurs for 6-12 months
causes more severe disease (more RBC able to be infected)
associated with drug resistance
only early ring form trophozoites found in blood smears
banana shaped gametocytes
high parasitemia index involving all ages of RBC
what are the key characteristics of plasmodium vivax
persistant exoerythrocytic stage - can relapse up to 40 years after initial infection
ca’t infect all peripheral RBCs
tinidazole - mechainsm
forms free radical that leads to cell destruction by inhibition of acetyl coA synthesis
tinidazole - metabolsm
p450, 3a4
can induce and inhibit
tinidazole - use
trichomoniasis, giardiasis, systemic E histolytica infection
drug of choice for trichomonas vaginalis
tinidazole
drug of choice for giardiasis
tinidazole
metonidazole - mechanism
same as tinidazole, more GI distress
form free radical that leads to cell destruction by inhibition of acetyl coA synthesis
giardiasis symptoms
sometimes asymptomatic
symptoms are mild diarrhea to abdominal pain to severe malabsorption syndrome
ingestion of cyst
trichomoniasis symptoms
persistant vaginal imflammation, discharge, itching and burning
infection in males is generally asymptomatic
sometimes asymptomatic
symptoms are mild diarrhea to abdominal pain to severe malabsorption syndrome
giardiasis
persistant vaginal imflammation, discharge, itching and burning
infection in males is generally asymptomatic
trichomoniasis
amoebiasis symptoms
majority are asymptomatic
vague non-specific abdominal symptoms to dystentery, abdominal pain, anorexia, weight loss, chronic fatigue
sometimes can produce abscesses of the liver and lungs
majority are asymptomatic
vague non-specific abdominal symptoms to dystentery, abdominal pain, anorexia, weight loss, chronic fatigue
sometimes can produce abscesses of the liver and lungs
amoebiasis
amoebiasis is caused by
Entamoeba histolytica
ingesting cyst
treatment of amoebiasis is with:
luminal drugs - paromomycin
systemic drugs - tinidazole (followed by paromomycin)
paromomycin - mechanism
binds 30S ribosome and prevents protein synthesis
paromomycin - clinical uses
drug of choice for asymptomatic luminal amebiasis
- iodoquinol used to be drug of choice for amebiasis but studies have shown association with optic atrophy and blindness
drug of choice for asymptomatic luminal amebiasis (e histolytica, extracellular)
paromomycin
paromomycin - drug interactions
decreases digoxin serum concentration by 30-80 percent
drug of choice for active intestianl and systemic infection
tinidazole
followed by course of paromomycin due to how much is absorbed in upper GI tract; T alone fails to eradicate trophozoites in lower GI tract
sleeping sickness is caused by:
african trypanosomiasis
what are the two subspecies that are human parasites
trypanosoma brucei gambiense
t. b. rhodesiense
infection by t b gamiense causes what symptoms?
fever, lymph node enlargement, generalized pain, muscle weakness
parasitic invasion of CNS leads to sleepiness
—> apathy, prgressive loss of coordiantion, tremor, paralysis, coma, finally death
fever, lymph node enlargement, generalized pain, muscle weakness
parasitic invasion of CNS leads to sleepiness –> apathy, prgressive loss of coordiantion, tremor, paralysis, coma, finally death
intense itching in late stage disease
usually greater than 2 years for full progression
t b gamiense
fever, lymph node enlargement, generalized pain, muscle weakness
parasitic invasion of CNS leads to sleepiness –> apathy, prgressive loss of coordiantion, tremor, paralysis, coma, finally death
intense itching in late stage disease
all occuring within the first few months of infection
t b rhodesiense
the non CNS stage of tryptanosomiasis is called
hemolymphatic stage
treatment of hemolymphatic stage of tryptanosomiasis is
suramin
suramin - mechanism
inhibits energy metabolism
mechanism isnt quite clear
suramin - resistance
no resistance after 80 years of usage
suramin - admin
IV only, no oral
suramin - use
drug of choice for tryptanosomiasis (t b gambiense, t b rhodeiense) in early stages before CNS involvement
rarely used on its own for tb gambia - often give with pentamidine
drug of choice for tryptanosomiasis in early stages before CNS involvement
rarely used on its own - often give with pentamidine
suramin
pentamidine - use
non CNS t b gambia with suramin
not useful against t b rhodeiense
doesnt cross the BBB so not useful for infections inbrain or spinal cord
pentamidine - mechanism
binds/causes DNA deletion via topoisomerase II
pentamidine - side effects
adverse effects in about half patients
-headaches, dizziness, breathlessness, tachycardia
impaired renal function in about a quarter of patients
damages pancreatic islet cells - can cause hypoglycemia and diabetes
what drugs are used to treat t. b. rhodeiense/gambia when there is CNS involvement (late stages)
melarsoprol
eflornithine
melarsoprol - mechanism
thought to inactivate many enzymes by reactive sulfhydryl groups
mammalian cells can deactivate drug faster than trypanosomas
also selective permeability of the parasite membrane
melarsoprol - use
t b rhodeiense and t b gambia
if t b rhodeiense relapse, use eflornithine
if t b gambia are not cured by melarsoprol, they rarely will respond to a second treatment
melarsoprol - side effects
ver toxic encephalopathy phlebitis peripheral neuritis anemia in patients with G6P deficiency
eflornithine - mechanism
irreversible inhibition of ornithine decarboxylase - interferes in production of necessary macromolecules (polyamines, putrescine, spermine, spermidine)
eflornithine - use
for treatment of late stage trypanosomiasis with CNS involvement caused by t b gambiense
not effective against t b rhodesience
what drug would be used to treat trypanosomiasis with CNS involvement caused by t b gambiense
elfornthine
what drug would be used to treat trypanosomiasis with CNS involvement caused by t b rhodesience
melarsoprol
America trypanosomiasis is also called
chagas disease
american trypanosomiasis is caused by:
the flagellate trypanosoma truzi transmitted by the reduviid bug (kissing bug)
describe how a person is infected with america trypanosomiasis
deposition of bug feces containing trypomastigotes (trypanosomes) onto skin
the trypanosomes get transmitted into skin, into blood by the bite or itching, or scratching skin with fingers contaminated with bug feces
trypanosomes then become amastigote (loss of flagella)
replication
then turn back to trypanosomes which lyse the cell and emerge to invade other cells or reinfect reduviid bug
-exhibit preference for cardiac, smooth, skeletal muscle and nerve cells
what is the presentation of chagas disease
acute phase - anemia, weakness, nervous disorders, chills, muscle and bone pain, variable heart failure
-most severe in children, death might result in a matter of weeks
chronic phase - more common in adults
-central and peripheral nervous system dysfunction and damage to heart and maybe esophagus, colon
what is the drug of choice for chagas disease
nifurtimox
nifurtimox - use
useful for treating trypomastigote but not amastigote phase of chagas disease
(ineffective for treating chronic, intracellular t. cruzi)
nifurtimox - mechanism
produces oxygen free radicals
parasite does not have enzymes to inactivate these ROS and is more sensitive to human host
leishmania is trasmitted by:
promastigote through the pite of a sandfly
the systemic form of leishmaniasis caused by leishmania donovani is called
kala azar - parasite gets into macrophages and lyses them
the two cutaneous forms of leishmaniasis are:
L tropica (old world cutaneous) l braziliensis (new world cutaneous)
the drug of choice for leishmaniaiss (cutaneous and systemic)
sodium stibogluconate
sodium stibogluconate - mechanism
interferes with glycolysis and fatty acid oxidation, inhibiting energy production
malaria is caused by
protozoa from plasmodiidae
falciparum (malignant tertian)
vivax (benign tertian)
malariae, ovale (mild)
what is the alternative treatment for kala azar
pentamidine
plasmodiidae - life cycle
sporozoites are injected into blood stream
form schizonts in the liver
asexual reproduction –> merozoites (pre-erythrocytic phase)
merozoites enter RBC, initiating erythrocytic phase
transforms back into schizont, asexual repro –> merozoites that invade other erythrocytes
what drugs are used to treat malaria caused by plasmodiidae
chloroquine mefloquine pyrimethamine and sufodoxine atovaquone and proguanil artemether and lumefantrine primaquine
what drug is used to treat the exo-erythrocytic cycle (of p vivax, p ovale)
primaquine
what drugs can be used to treat the erythrocytic phase of p vivax, ovale, faciparum, and malariae
chloroquine
mefloquine
what drugs are used to treat the erythrocytic phase of p falciparum (resistant forms)
pyrimethamine + sulfadoxine
artemether + lumefantrine
what drugs are used to treat the erythrocytic phase of malaria
chloroquine mefloquine pyrimethamine + sulfadoxine artemether + lumefantrine atovaquone + proguanil
what other non-protozoan parasitic drugs are used to treat chloroquinon-resistant strains of malaria int he exo-erythrocytic phase
tetracycline
doxycycline
chloroquine - use
erythrocytic phase of p vivax, ovale, falciparum, malariae
cloroquine, mefloquine - mechanism
blocks heme polymerization
chloroquine, mefloquine - toxicity
hemolysis in patients with G6P deficiency
mefloquine - use
erythrocytic phase of p vivax, ovale, falciparum, malariae
pyrimethamine + sulfoxadine - use
erythrocytic phase of p falciparum
pyrimethamine + sulfoxadine - mechanism
blocks folic acid synthesis
pyrimethamine - inhibits reduction of FH2 to FH4
sulfoxadine - inhibits synthesis of precursor to FH2
pyrimethamine + sulfoxadine - side effects
bone marrow suppression
stevens johnsons syndrome
atovaquone + proguanil - mechainsm
selective inhibitor of parasite mit ETC (atovaquone)
inhibition of dihydrofolate reductase (proguanil)
atovaquone + proguanil - use
use of atovaquone alone = 30% faulure
use of the two together = 100% cure rate
against erythrocytic phase of
artemether + lumefantrine - mechanism
free radicals and inhibition of heme polymerization
primaquine - mechanism
interfers with pyrimidine synthesis and mitochondrial ETC
primaquine - toxicity
hemolysis in patients with G6P deficiency
primaquine - use
exo-erythrocytic phases of p vivax and p ovale
has ability to prevent drug relapses
steven-johnson syndrome is also known as
exfoliative dermatitis
hemolytic anemia occurs in patients with G6P DH mutation
many children play piano softly
melarsoprol chloroquine primaquine pyrimethamine sulfadoxine
