Antiparasitics Flashcards
Random US parasites
Helminth infections in over 1 million Toxocara (roundworms) from dogs and cas are 14%pop malaria~2000 year trichonomas vag~ 3 million Giardia: 10% population
Infection of parasites associated with
poor economic conditions
encysted tapes in 25% inner city children and leading cause of seizures in kinds in hispanice
Cure vs control
have to eradicate several staes of parasite in host
-enZ unique to host and indespendible only to parasite
Nematode (roundworm) cycle
see eggs in feces–> then will hatch into a filiraform to pentrate skin and hang in our small intestine
Damages microtulbes
inhibits glycogen uptake
can’t move or get E… DEATH you nasty roundworm!
Mebendazole
mictrotubule destruction… now they can get glycogen and they can’t move!
effective for many intestinal roundworms and kills some ova… damages microtubules
Mebendazole
Use of Mebendazole
kills intestinal roundworms and some ova
Absorption of Mebendazole
low systemic bioavailability = low systemic toxicity
Albendazole uses
Echinococcus or cuteanous larval migrans and neurocystocerosis d/t Taenia solium
Used for echinoccosus or cutaneous larval migrans or neurocysticercosis due to Taenia solium
Albendazole
EICK.. they’re all bendy under my skin and in my BRAIN!
same as mebendazole, liver –>albendazole sulfoxide (active)
good systemic distribution
Albendaozle
EICK.. they’re all bendy uder my skin and in my BRAIN!
How is albendazole differenet from mebendazole
converted quickly be liver to active form for better distribution which is why is
Mech of Albendazole in depth
fuck with microtubules
inhibits glucose uptake
can’t get food or move = die
What is special about albendazole metabolite
more activated by liver and great distribution
Side effects of Albendazole
duh.. elevates hepatic enZ bc converted in liver… and makes tummy hurt
affects energy metabolism via inhibition of mitochondrial fumarate reductase in HOOKWORMS
Thiabendazole
tHiabendazole has an H… hookworms
MEch of Thiabendazole for HOOKWORMS
I’d be FUMING if i had hookworms
affects E metabolism
inhibiting mitochondiral fumarate reductase in hookworms
(I’ld be FUMING if i had hookworms)
Mech of Thiabendazole for Strongyloidesl
inhibits assembly of parasitic microtubules.
Thiabendazole uses:
Strongyoids
cuteanous larva migrans from dog or cat hookworms
Strongyloides
cuteanous larva migrans from dog or cat hookworms
Thiabendazole
absorption of Thiabendazole
oral form rapidly absorbed
side effects of thiabendazole
nauseua, vomit, dizzy
Pyrantel Pamoate mechanism
depolarizing neuromuscular blocker, causing spastic paralysis of worm
Pyrantel Pamoate causes dePPPPPolarization and PPPPParalysis
uses of Pyrantel Pamoate
hookworm, pinworm, roundworm
increase Ca++ permeability.. causes muslce cnx… spastic paralysis
Praziquantel causes PPPPPPermeability
Mech of Praziquantel
increase Ca++ permeability.. causes muslce cnx… spastic paralysis
(PPPPPraziquantel… increase PPPPermeability)
drug of choice for Schisotosoma
Praziquantel
I pray this Schits over soon”
Use of Praziquantel
Schistosomiasis (also for taneia solium to prevent neurocysteriocorcosis)
Tape worm drugs
Praziquantel, Albendazole, Paromomycin sulfate
good activity for schistosomiasis but also for tania solium bc kills eggs to you can avoid cysticercosis
Praziquantel
Used to treat neurocysticercosis
Albendazole (be careful in poeople with seizures)
Used as 3rd choice for those that don’t tolerate Praziquantel or Albendazole for tapeworms
Paromomycin sulfate
“MOM.. i have tape worms”
Key with anti-malarials
don’t prevent infection.. they only prevent progression to symptomatic malaira
____ in mosquito salivary gland are injected into human blood
Sporozoites
Exoerythrocytic stage—
sporozoites multiply in liver to form tissue schizonts
Escape from liver into bloodstream as_____, which begins the erythrocytic stage; the merozoites invade red blood cells and multiply in them to form
merozoites
blood schizonts
Infected erythrocytes eventually rupture releasing a new crop of ______ this erythrocytic cycle may be repeated several times
merozoites;
What form are we always going to target with anti-malarial drugs
always the blood schizonts
• have only one cycle of liver cell invasion and multiplication (liver infection ceases
spontaneously in
P. falciparum and P. malariae
have dormant hepatic stage (hypnozoite) that can cause relapses
• treatment requires elimination from both the liver and blood
P. vivax and P. ovale •
Liver has 5 letters and so do these malaria
Blood schizonticide:
parazitized erythrocytes concentrate the drug 25 fold by pH dependent mechanism into acidic vacuoles
Chloroquine
(think chloride because its negatve and will go to low pH
which trophozoites are suspeptible to Chloroquine (quine sounds like 4… all are suspetible and stops heme quads!)
ones actvely degrading hemaglobin… the chloroquine inhibits heme polymerization and the heme accumulate to toxic levels === death!
Use of Chloroquine
all 4 species
will eradiate P. malariae and P. falciparum but wont cure P. vivax and ovale (still have liver form)
Tx all 4 species
will eradiate P. malariae and P. falciparum but wont cure P. vivax and ovale (still have liver form)
Chloroquine
careful for P.falciparum resistance
Side effect of chloroquine
visual impairment
chloroquine… 4 eyes!!!! b’c quine sounds like quad… also for all four… alsp think stops heme from going to 4
Mech of Mefloquine
sim to chloroquine
use to tx chloroquine resistant P.falciparum and P.vivax and as prophylaxsis in chloroquine resistant areas
Mefloquine
What pts should not recieve mefloquine
pts with eplilepsy or pychiatric disorders
Black box warning for Mefloquine
psychiatric effects like anxiety, paranoa and depression as well as vestibular effects
“Me-floquine will make ME crazy!”
◊ ubiquinone analog
inhibits malarial mitochondrial election transport ~ cyt bc1
fucks up pyrimdine synthesis
atovaquone
prodrug activated by hepatic CYP2C9 to inhibi malarial dihydrofolate reductase to block folate synthesis— pyrimidine synthesis
Proguanil
“pro as in prodrug”
These two will inhibit protozoal pyrimidine synthesis
Atovaquone
Proguanil
Mech of Atovaquone
think ABC’s~~~ goes A for atovaquone and BC for cyctochorm BC1
ubiquinone analog
inhibits malarial mitochondrial ETC by disrupting Cyt BC1
Fucks up their pyrimidine sythesis
Mech of Proguanil
prodrug activated by hepatic CYP2C9
inhibits malarial dihydrofolate reductase block folate synthesis— pyrimidine synthesis
Why do we use Proguanil and atovaquone together for chloroquine resistant P.falciparum
because synergistic effect on mitochondria when given together and fewer side effects
Mech of quinine
similar to chloroquine
RBC infected with parasites…inside acidic vacuoles which concentrates the drug. The drug prevents the hemes that the trophazoites are degrading from polymerizing into a toxic free heme… build up toxic heme = death
Uses of Quinine
Schizonticide for all four
alternative for P.Falciparum resistant to Chloroquine
similar to chloroquine
RBC infected with parasites…inside acidic vacuoles which concentrates the drug. The drug prevents the hemes that the trophazoites are degrading from polymerizing into a toxic free heme… build up toxic heme = death
Quinine and Mefloquine
Diff side effects
Both Quinine and Mefloquine are alt for Chloroquine reistant P. Falciparum, whats the differece
Mefloquine: black box on pyschiatric issues and epilepsy
Quinine: Cinchonism, cardiate effects simular to qunidine or nausea
Side effects of quinine
cinchonism: headache, visual disturbance, dizziness, tinnitus
GI
cardiac effects similar to quinidine
cinchonism: headache, visual disturbance, dizziness, tinnitus
gastric irritation, nausea, vomiting
cardiac effects similar to quinidine
sides for quinine
Doxycycline mech
depress dihydroorotate
dehydrogenase activity,
can’t make pyrimidines
fucks with dihydroorotate DH activity
then the malaria can’t make pyrimides
Mech of Doxycycline
“Doxy got all those D’s
Dihidroorotase DH”
effective for multidrug-resistant P. falciparum, especially in combination with quinine
• also for malarial prophylaxis
Doxyclycine
Drug to kill liver hypnoschizots
Primaquine
Mechanism of Primaquine
act as oxidants will kill liver hypnozoites
radical cure or terminal prophylaxis of P. vivax and P. ovale because it will kill dormant liver schizonts; usually given at end of therapy with chloroquine; for travelers to malarious regions, primaquine is usually given after return home
Primaquine
radical cure for P. vivax and P. ovale and used with drugs to kill blood schizonts
Primaquine
Drug can also be used to tx Pneumocystisi jiroveci pneumonia in AIDS pts
Primaquine
uses of Primaquine
liver schizonts: P. vivax and P. ovale and pneumocystis jirovveci
Side effects of primaquine
hemolytic rxns in those with G6P DH deficiency
see hemolytic rnx in those with GP6 deficiency
Primaquine
