Protozoa

Amebiasis – Entamoeba histolytica

• Treatment directed against the trophozoites
• Luminal – Diiodohydroxyquinoline (Iodoquinol)
• Invasive – 1) Metronidazole + Iodoquinol

2) Emetine + Iodoquinol

3) Chloroquine + Iodoquinol (not understood for ameba)

Balandidiasis – Balantidium coli

• Iodoquinol + tetracycline
• Tetracycline acts on bacteria that the parasite is dependent upon

Giardiasis – Giardia lamblia

• DRUG OF CHOICE – Metronidazole
• Also Quinacrine

Cryptosporidiosis – Cryptosporidium sp

• oocysts that contain four sporozoites, autofluorescent and acid fast
• immediately infective
• in healthy people – resolves on its own
• NO DRUG THERAPY KNOWN

Cyclosporiasis – Cyclospora cayetanensis

• oocysts require 1-2 weeks in the environment to develop to an infective stage
• oocysts contain 2 oocysts, each with 2 sporozoites
• use: Trimethaprim-Sulfamethoxazole

Malaria – Plasmodium vivax, P. malariae, P. falciparum, P. ovale

• Prophylaxis

Ø  active against sporozoites and thus prevent the acquisition

Ø  Use: Primaquine

• Schizontal drugs – used to treat an acute attack

Ø  Chloroquine (resistance has emerged)

Ø  Quinine – for resistant P. falciparum – add Sulfadiazine and Pyrimethamine or Trimethaprim

• Anti-relapse drugs

Ø  aimed at attacking the hypnozoite (liver schizonts)

Ø  prevents relapses caused by P. falciparum and P. malariae

Ø  Use: Primaquine

• Gametocidal and sporontocidal – to prevent transmission via mosquito vectors

Ø  Use: Primaquine

Toxoplasmosis – Toxoplasma gondii

• get it from cat feces
• use: Pyrimethamine
• can combo Sulfadiazine

Amebic meningoencephalitis – Naegleria fowleri

• no treatment

Trichomoniasis – Trichomonas vaginalis

• use: Metronidazole (Flagyl)

Drugs used to treat Protozoa

Chloroquine

• rapidly absorbed
• slowly excreted
• sequestered in the liver (used widely to treat liver abscesses)
• ineffective against intestinal trophozoites
• In malaria, MOA thought to be due to the interference with the feeding mechanism of the Plasmodium

Ø  the hemoglobin that is taken up by the Plasmodia is normally used as a source of energy.  The toxic products are converted to non-toxic polymerized form by heme-polymerase.

Ø  Chloroquine is thought to inhibit heme polymerase

• Invasive amebiasis, Active Malaria

Diiodohydroxyquinoline (Iodoquinol)

• unknown mechanism of action
• lumenal amebiasis, Balandidiasis

Emetine

• inhibits protein synthesis
• eliminates the diarrhea
• high toxicity: CI in patients w/ cardiac disease
• Invasive Amebiasis

Metronidazole (Flagyl

• ferrodoxin-like electron transport proteins use the NO₂ group of Flagyl which leads to derivatives that bind to proteins and DNA; prevents DNA replication
• Invasive Amebiasis, Trichomoniasis

Primaquine

• unknown mechanism of action
• Prophylaxis, Anti-relapse, and Gametocidal of Malaria (effective against sporozoites, hypnozoites)

Pyrimethamine

• inhibits DHF reductase in Folic acid synthesis
• can use trimethoprim as a substitute
• used in Malaria against the schizonts to treat an acute attack
• also used in Toxoplasmosis

Quinine

• Unknown mechanism of action
• General protoplasmic poison
• Active malaria that is resistant to Chloroquine
• Used in combo with Sulfa-Pyrimethamine (Trimethoprim)

Quinacrine

• unknown mechanism of action
• 2^nd line for Giardiasis

Sulfadiazine

• inhibits pteridine synthase
• structural analog of PABA
• prevents synthesis of Folic Acid
• Also, in malaria can use sulfalene because of longer DOA and slower excretion.
• used to treat acute attacks of Malaria (Schizonts)

Trimethaprim-Sulfamethoxazole

• Cyclosporiasis

Nematodes

Pinworms – Enterobius vermicularis

Whipworms – Trichuris trichiura

Ascariasis – Ascaris lumbricoides

Hookworms – Ancyclostoma duodenale & Necator americanus

• Use: Mebendazole for all

Strongyloidiasis – Strongyloides stercoralis

• Use Ivermectin & Thiabendazole

Trichinosis – Trichinella spirallis

• treatment aimed to reduce the inflammation caused by the migrating and encapsulated larvae
• Use: anti-inflammatory agents Salicylates & Corticosteroids

Cutaneous and Visceral Larva Migrans – Toxocara Canis, Ancyclostoma brasiliensis, Ancyclostoma caninum

* Use Thiabendazole for both cutaneous and visceral forms

Drugs to treat Nematodes

Ivermectin

• mechanism

Ø  binds to GABAnergic nerves, stimulating GABA release and enhancing postsynaptic GABA binding

Ø  paralysis

• Strongyloidiasis

Mebendazole

• Mechanism

Ø  acts by binding to free tubulin, thus inhibiting tubulin polymerization

Ø  leads to inhibition of secretory granule transport and movement of other subcellular organelles

Ø  Glucose transport is also inhibited

• Pinworms, Whipworms, Ascariasis, Hookworms

Thiabendazole

• mechanism

Ø  similar to Mebendazole – interferes with microtubule aggregation in nematode cells

Ø  ALSO, thought to inhibit fumarate reductase and the ability of fumarate as an electron acceptor

• Strongyloides, Visceral and Cutaneous Larva Migrans

Salicylates and Corticosteroids

• trichinosis

Tapeworm Infections

Beef Tapeworm – Taenia saginata

Pork tapeworm – Taenia solium

Rat tapeworm – Hymenolepsis diminuta

Dwarf Tapeworm – Hymenolepsis nana

Dog tapeworm – Dipylidium caninum

Fish tapeworm – Diphyliobothrium

• Use Niclosamide and Praziquantel
• Both are active against the adult forms

Cysticercosis – Taenia solium

Hydatid disease – Echinococcus granulosus

• larval form
• Use: Albendazole for both

Drugs used to treat Tapeworm infections

Niclosamide

• mechanism

Ø  lethal for the scolex and segments of cestodes, but not for the ova

Ø  inhibits the parasites mitochondrial anaerobic phosphorylation of ADP to ATP

• effective against all adult tapeworm infections

Praziquantel

• mechanism

Ø  causes paralysis

Ø  increases the cell membrane permeability to Ca²⁺, which results in tetanic contractions followed by paralysis

Ø  vacuolization and destruction of the tegument lead to death of the worm

• effective against all adult tapeworm infections

Albendazole

• mechanism

Ø  blocks glucose uptake by larval and adult stages of tapeworms

• used for cysticercosis, hydatid disease

Trematode Infections

Shistosomiasis – Schistosoma mansoni, Schistosoma japonicum, Schistosoma hematobium

• all transmitted by cercaria
• Use: Praziquantel
• Same mechanism of action as for tapeworms.

Tags: Amebiasis, Amebic meningoencephalitis, Balantidium coli, Cryptosporidiosis, Cyclospora cayetanensis, Diphyliobothrium, Dipylidium caninum, Emetine, Entamoeba histolytica, Hymenolepsis diminuta, Hymenolepsis nana, lasmodium vivax, Malaria, Naegleria fowleri, Protozoa, Schizontal drugs, Taenia saginata, Taenia solium, Tapeworm Infections

This entry was posted on Saturday, August 1st, 2009 at 5:00 am and is filed under Pharmacology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.