Antiparasitics Flashcards
Prevalence in the USA
Helminth Infections Toxocara Malaria Amebiasis Giardia Trichomonas vaginalis Infections associated with poor economic conditions
Approach to Antiparasitic Chemotherapy
Target enzymes/function unique to parasite
Target enzymes indespinsable to them
Target common functions but different pharmacological properties
Chemotherapy of Nematode (Roundworm) Infections
Mebendazole
Albendazole
Thiabendazole
Pyrantel Pamoate
Mebendazole
Poor oral absorption Intestinal roundworms Kills som Ova Broad coverage Poorly absorbed; low systemic toxicity
Albendazole
Echnococcus
Unlableled use: cutaneous larval migrans
Well distributed
Elevated hepatic enzymes, abdominal pain, nausea, vomiting, headache
Pyrantel Pamoate
Hookworm, pinworm, and roundworm
OTC as Pin-X for pinworm
Not for whipworm (Trichuris)
Poorly absorbed so for mild GI symptoms
Thiabendazole
Strongyloides, cutaneous larva migrans (“disseminated” dog or cat hookworm)
oral or topical if limited
Rapidly absorbed: nausea, vomiting, dizziness
Trematode Infections
Praziquantel
Praziquantel
Drug of choice for Schistosoma
Some activity against other trematodes
Good activity for Cestodes
Taenia solium also kills eggs (which are infective to man) therby avoiding cysticercosis (PREVENTIVE FOR NEUROCYSTOCERCOSIS)
Side effects: abdominal discomfort, nausea
Cestode (tapeworm) Infections
Praziquantel
Albendazole
Paromomycin Sulfate
Albendazole
Cestode Infections
Systemically distributed
Treat neurocysticercosis
Paromomycin Sulfate
3rd choice for those who can’t tolerate the other drugs
Treats Cestode Infections
Antimalarial Drugs
None are preventive of infection
Only prevent progression to systemic malaria (prophylaxis)
Prophylaxis
For P.vivax and ovale target hepatic form for 14 days after leaving endemic area
For all 4 species, target RBC forms whilein endeic area and continue for 4 weeks after leaving endemic area
Chloroquine
First effective synthetic antimalarial
Basic drug in acidic vacuole of parasite
Parasitized erthrythrocytes concentrate the drug (by pH mechanisms)
Inhibits the heme polymerization allowing heme to accumulate to toxic levels and damage the parasite
Uses: malarial prophylaxis (all 4 species if they are sensitive) but not as effective for chloroquine-resistant strains of P. falcipairum and P. vivax
Treatment to eradicate P. malariae and chloroquine sensitive P. falciparum and Target blood schizonts of P. vivax and ovale (doesn’t target liver hypnozoites)
Side Effects: visual impairment
Mefloquine
Mechanism: similar to chloroquine
against blood schizonticide
Use: treatment of chloroquine resistant P. falciparum and P. vivax
prophylaxis in chloroquine resistant areas
Contrainidcated: epilepsy and psychiatric disorders
Side effects: psychiatric effects (anxiety, paranoia, depression) and vestibular effects (dizziness, vertigo)
Atovaquone and Proguanil (malarone)
Both block pyrimidine synthesis
Atovaquone- selectively inhibits malarial mitochondrial electron transport (cytochrome bc1) and disrupt pyrimidine synthesis
Proguanil- inhibit malarial dihydrogolate reductase and block folate synthesis
Use: prevention and treamtent of chloroquine resistant P. falciparum
Side Effects: nausea, diarrhea, vomitin, rash
Quinine
Similar to chloroquine
Use: blood schizonticide: all four malarial parasites
severe acute attacks
alternative for chloroquine resitant P. falciparum
Side Effects: cinchonism (headache, visual disturbance, dizziness, tinitus), gastric irritaiton, nausea, vomiting, cardiac effects like quinidine
Doxycycline
Antimalarial mechanisms: decrease malarial protein synthesis, depresses dihydoorotate dehydrogenase activity (interfere with pyrimidine synthesis)
Use: treat of multidrug resistant P. falciparum and prophylaxis of chloroquine resistant P. falciparum
Primaquine
Uses: kills liver hypnozoites, radical cure/terminal prophylaxis of P. vivax and P. ovale (in conjunction with blood schizonticide)
pneumocystis jivoreci pneumonia in AIDA patients in combination with clindamycin
Side Effects: hemolytic reactions in those with G6P dehydrogenase deficiency
Therapy of Amebic Dysentery
Tissue Amebicides- metronidazole (symptomatic infections)
Lumnial amebicides- iodoquinol, paromomycin suflate (alone for asymptomatic infections and given with tissue amebicide)
Metronidazole
Tissue amebicide
Symptomatic infections
Giardia lamblia
Trichomonas Vaginalis
Iodoquinol
Luminal amebicide
Side Effects :diarrhea, other GI symptoms, contraindicated in those with hypersinsitive to iodine
Paromomycin SUlfate
luminal amebicide
aminoglycoside that inhibits protein synthesis
oral dose is poorly absorbed= low incidence of systemic side effects
Side effects: diarrhea, nausea, vomiting, epigastric pain
Nitazoxanide
Giardia lamblia
Cryptosporidium parvum
GI side effects: diarrhea, nausea, abdominal pain
Inhibits pyruvate: ferredoxim oxidoreductase, disrupting anaerobic energy metabolism
Atovaquone
Pneumocystis jivoreci (carinii) prophylaxis or treatment
Toxoplasma gondii
Used with proguanil- prevention and treament of chloroquine resistant P. falciparum
Treatment of Pneumocystis Jivoreci
Trimethoprim+suflamethoxazole (TMP-SMX)
Clindamycin+ primaquine
Atovaquone
Dapsone
