C.3. Antiprotozoal and antihelminthic drugs Flashcards
list the drugs for Malaria (protoza)
Chloroquine Mefloquine Quinine Artemether Lumefantrine primaquine Atovaquone/ Proguanil (Malarone)
what is pyrimethamine/sulfadoxine’s potential role in Malaria treatment?
treatment+prophylaxis of chloroquine resistant strains
what is the potential role of dapsone in malaria treatment?
prophylaxis use
what is the potential role of doxycycline in malaria treatment?
prophylaxis in areas with multidrug-resistant P. falciparum
where is the chloroquine prophylaxis regimen given?
in areas with no known resistant P. falciparum strains.
where is the Malarone prophylaxis regimen given?
in areas with chloroquine-resistant P. falciparum strains.
what is the mechanism of chloroquine?
inhibit heme polymerization into hemozoin–> intracellular accumulation of heme is toxic to the parasite
how are the antimalarial drugs given?
oral
quinine and Artemether–> IV in severe infections
pharmacokinetic property of chloroquine
antacids ↓ oral bioavailability
what are the uses of Chloroquine?
- treatment+ prophylaxis in areas without resistant P. falciparum strains. (1st line agent)
- treatment of P. vivax and P. ovale.
adverse effects of chloroquine
mild effects in low doses: GI distress, rash, headaches
high doses: retinal damage, auditory damage, QT prolongation
what additional use does hydroxychloroquine have other than being an anti-malaria agent?
used in autoimmune disorders: RA, SLE and Sjogren syndrome
what anti-malarial agents are blood schizonticide?
chloroquine mefloquine quinine artemether lumefantrine
which antimalarial agent is a tissue schizonticide?
primaquine
kills schizonts in the liver
which anti-malarial drugs have an unknown mechanism?
Mefloquine
Lumefantrine
what is the use of Mefloquine
treatment+ prophylaxis in areas with resistant P. falciparum strains. (1st line agent)
what is the mechanism of quinine?
inhibit protozoal DNA replication
what is the use of quinine?
treatment of multidrug-resistant malaria
*may be used in combination with doxycycline or clindamycin
side effects of mefloquine (4)
- GI distress
- skin rash
- conduction abnormalities
- neurotoxicity (seizures)
side effects of quinine (4)
- Cinchonism ( GI distress, headache, vertigo, blurred vision, tinnitus )
- acute hemolysis in G6PD deficient patients
- conduction abnormalities
- teratogenic
what is Quinidine and when is it used?
antiarrhythmic agent, an isomer of quinine
can be used IV in the treatment of severe complicated P. falciparum malaria
adverse effects of Quinidine
cinchonism, QRS an QT prolongation with risk of syncope
mechanism of Artemether and Artesunate
production of free radicals within the plasmodium food vacuoles
indications of Artemether and Artesunate
treatment of multidrug-resistant malaria
effective against quinine resistant strains
side effects of Artemether and Artesunate
nausea, vomiting, diarrhea
side effect of Lumefantrine
QT prolongation
indication of Lumefantrine
in combination with artemether against P. falciparum
why Artemether can’t be used for prophylaxis?
T1/2 is too short
side effects of Malarone (atovaquone+Proguanil)
GI distress, fever, rash
indication of Malarone
treatment+ prophylaxis of multidrug-resistant P. falciparum malaria
mechanism of Atovaquone
disrupts mitochondrial metabolism
mechanism of Proguanil
antimetabolite (↓folate synthesis)
MoA of Primaquine
generates metabolites that act as oxidants
side effects of Primaquine
- GI distress
- rash, headache
- acute hemolysis in G6PD deficient patients
- teratogenic
what are the antibacterial and antiprotozoal indications of metronidazole?
antibacterial–> anaerobic gram - (mostly)
antiprotozal–> giardia lamblia, trichomonas vaginalis, antamoeba histolytica
is metronidazole an inhibitor of the CYP450 enzyme?
yes
mechanism of metronidazole
it undergoes reductive bioactivation of its nitro group –> form reactive free radicals –> interfere with nucleic acid synthesis
how is metronidazole given?
oral and parenteral
matabolism of metronidazole
hepatic
side effects of metronidazole
- GI distress
- leukopenia
- CNS effects (neuropathy)
- dark discoloration of urine
- metallic taste
- Disulfiram like reaction with ethanol (nausea, vomiting, headache, hypotension)
treatment of toxoplasmosis?
pyrimethamine/sulfadiazine
what is the treatment of Leishmaniasis?
Stibogluconate
what is the treatment of Trypanosoma Cruzi (Chagas disease)?
Nifurtimox
what is the treatment of Trypanosoma brucei (sleeping sickness)?
“PMS”
Pentamidine- early infection stage
Melarsoprol- advanced infection–> CNS involvement
Suramin- early infection stage
what are the drugs for helminthic infections?
“NIV”
Niclosamide
Ivermectin
Mebendazole
how are helminthic drugs given?
orally
what is the mechanism of action of Mebendazole?
inhibits microtubule synthesis
inhibits glucose uptake
indications for Mebendazole (4)
- Ascaris lumbricoides
- Enterobius vermicularis (Pinworm infection)
- Trichuris Trichuria (whipworm infection)
- Visceral larva migrans
side effects of mebendazole
- GI distress
- Granulocytopenia. alopecia (in high doses)
- teratogenic
treatment of amebiasis (Entamoeba histolytica infection)
may require co-administration of metronidazole with luminal active agents (Paromomycin or Diloxanide)
what does it mean that Mebendazole is a luminal active agent?
it means that 90% of the given dose is not absorbed –> stays in the lumen of the intestine
does Ivermectin cross the BBB?
no
what is the mechanism of Ivermectin?
facilitates GABA-mediated transmission in nematodes and causes immobilization of parasites
mechanism of Niclosamide
Uncoupling oxidative phosphorylation
indications of Ivermectin
- intestinal nematodes–> Strongyloids stercoralis
2. tissue/ blood nematodes–> cutaneous lrava migrans, oncocerca volvulus
side effects of Ivermectin
reaction to the dying worms (can be managed with antihistamine and NSAIDS's) : fever, headache rash, pruritis joint and muscle pain hypotension lymphadenopathy
*TERATOGENIC
Indications of Niclosamide
TAPEWORMS:
- Taenia saginata (beef tapeworm)
- Taenia solium (pork tapeworm)
- Diphyllobothrium latum (fish tapeworm)
side effects of Niclosamide
GI distress, fever, rash
*generally well tolerated
