antiparisitics Flashcards
Approaches to antiparasitic chemotherapy
Selective chemotherapy: target enzymes/functions unique to parasite , target enzymes found in both host and parasite but are only indispensable only to parasite, target common biochemical functions of host and parasite but that have different pharmacologic properties in each
Cure vs control
mebendazole
MOA: selective damage to cytoplasmic microtubules
uses: effective for many intestinal roundworms, kills some ova
Admin: oral
Absorption/secretion: low systemic bioavailability; low systemic toxicity
SE: abdominal pain, diarrhea, neutropenia, hypospermia
albendazole
MOA: selectively damages cytoplasmic microtubules, liver quickly converts it to albendazole sulfoxide which is an active metabolite with good systemic distribution
Use: 1st choice for echinococcus, neurocysticercosis due to taenia solium, cutaneus larval migrans, treats nerocysticercosis
Admin: oral
Absorbtion: well distributed
SE: elevated heoatic enzymes, abdominal pain , nausea, vomiting, headache, leukopenia
thiabendazole
MOA: hookworms (affects energy metabolism via inhibition of mitochondrial fumarate reductase). for strongyloides (inhibits assembly of parasitic microtubules)
Use: strongyloides, cutaneous larva migrans, alternate agent for other round worm infections
Admin: oral or topical (if cutaneous larval migrans limited)
absorption/ex: rapidly absorbed, urine
SE: nausea, vomiting dizziness, anorexia
pyrantel pamoate
MOA: depolarizing Neuromuscular blocker, causing spastic paralysis of worm
Use: pinworm, hookworm, roundworm, (not effective against trichuris)
SE: GIT symptoms, headache, rash
praziquantel
MOA: increases cell membrane permeability to calcium, resulting in marked muscle contraction–paralysis
Use: drug of choice for all schistosoma, some activity against other trematodes, good activity against many cestodes, treats taenia solium will prevent neurocysticercosis, good activity against many cestodes
Admin: oral
SE: abdominal discomfort, nausea, rash fever
paromomycin sulfate
good activity against many cestodes, 3rd choice because release of viable ova
also an amebiasis- MOA: aminoglycoside-like inhibiting protein synthesis
luminal amebicide
SE: diarrhea, nausea, vomiting epigastic pain,
malaria life cycle
sporozoites in mosquito salivary gland are injected into human blood
Exoerythrocytic stage- sporozoites multiply in liver to form tissue schizonts
Excape from liver into bloodstream as merozoites, which begins the erythrocytic stage, and merozoites invade RBCs and multiply in them to form blood schizonts, rupture–> new crop of merozoites
during erythrocytic stage the gametocytes form and are released into blood where they are taken up by a mosquito
implications of life cycle for treatment
P. falciparum and p malaria: have only one cycle of liver cell invasion and multiplication (liver infection ceases spontaneously in 4 weeks), any treatment that eliminates the erythrocytic stage of infection 4 or more weeks after the initial infection will therefore cure these forms of malaria
P. vivax and P ovale: have dormant hepatic stage (hypnozoite) that can cause relapses, treatment requires elimination from both the liver and blood
Classification of antimalarials based on life cycle stage:
Tissue schizonticides: eliminate latent liver hypnozoites
Blood schizonticides: suppressive agents act on blood schizonts
chloroquine
MOA: blood schizonticide, selectively toxic to parasite because parasitized erythrocytes concentrate the drug 25 fold
only intraerythrocytic trophozoites that are actively degrading hemoglobin are chloroquine susceptible, polymerize potentially toxic free heme into unreactive hemozoin, chloroquine inhibts this heme polymerization allowing heme to accumulate to toxic levels
use: prevent attacks of all 4 species of malaria if they are chloroquine-sensitive, eradicate P malariae and chloroquine sensitive P. falciparum infections, will not effect a complete cure of P. vivax and ovale
SE: visual impairment, skin discoloration
mefloquine
similar to chloroquine, blood schizonticide for p falciparum and p vivax
use: treatment of chloroquine-resistant and multidrug resistant P. falciparum, used as prophylaxis in areas where organisms are resistant to chloroquine
SE: psychiatric effects: paranoia, depression, anxiety
vestibular effects: dizziness, vertigo
mefloquine is contraindicated in those with epilepsy or psychiatric disorders
atovoquone and proquanil
MOA: both drugs block pyrimidine synthesis, they are blood schizonticides. atovaquine ( selectively inhibits malarial mitochondrial election transport, disrupting protozoal pyrimidine synthesis). Proguanil ( a prodrug, activated inhibits malarial dihydrofolate reductase, blocking pyrimidine synthesis)
Use: prevention and treatment of chloroquine-resistant p falciparum
SE: GIT, vomiting, rash
quinine
MOA: similar to chloroquinine, blood schizonticide against all four malarial parasites
Use: agent of choice for severe acute attacks, treatment of chloroquine-resistant p falciparum
SE: cinchonism (headache, visual disturbance, dizziness, tinnitus, gastric irritaions, cardiac issues
doxycycline
MOA: decreases malarial protein synthesis and depresses dihydroorotate dehydroorotate dehydrogenase activity, thereby interfering with pyrimidine synthesis
Uses: multidrug resistant p falciparum, also for malaraial prophylaxis of p falciparum
primaquine
MOA: oxidants
Uses: radical cure or terminals prophylaxis of p vivax and p ovale because it will kill liver schizonts, should be used in conjunction with blood schizonticide
in combo with clindamycin to treat pneumocystis jiroveci (carinii) pneumonia in AIDs pts
SE: hemolytic reactions in those with G6PD
