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Micro 5 Antiparasiticals Anthelmintics, Pediculicides, Miticides, Antifungals

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Micro 5 Antiparasiticals Anthelmintics, Pediculicides, Miticides, Antifungals Micro 5 Antiparasiticals Anthelmintics, Pediculicides, Miticides, Antifungals PHRM 203 Allison Beale Helminths The parasitic worms • Phylum/Class Nematodes – “Thread” worms • Class Cestodes • “Round” worms – “Tape” worms – Ascaris lumbricoides – Anisakis sp. • Hymenolepis nana • “Whip” worms • Taenia solium - Neurocysticercosis = most – Trichuriasis common brain parasite • “Filarial” worms • Echinococcus granulosus - – Onchocerca volvulus Hydatid d. – Wuchereria bancrofti • “Spiral” worms • Class Trematodes – Trichinela spiralis – “Flukes” • “Hook” worms • >20K species (Strongyles) • Blood versus tissue – Necator americanus – Schistosomiasis • “Pin” worms – Fascioliasis – Enterobius vermicularis Phylum Platyhelminths PHRM 203 - Anthelmintics & 2 Antifungals % World Population with Helminth infections 30% AscarisN ~22% HookwormsN ~18% TrichurisN ~14% FilariasN 10% EnterobiusN 4% SchistosomesT 2% Tape WormsC N 1% Trichinella (Now contoled in US by Federal Swine Healt Protcton Act) Key: N= Nematode; C = Cestode; T=Trematode PHRM 203 - Anthelmintics & 3 Antifungals Cestodes (tape worms) Hymenolepis Echinococcus nana granulosis Human “Dog” tape worm tape worm Proglod – Treatment: Albendazole, 80K eggs ea. Mebendazole or Praziquantel Taenia solium Scolex Pork tape worm PHRM 203 - Anthelmintics & 4 Antifungals Trematodes (flukes): Schistosomes Ascites a result of eggs physically blocking hepatic blood vessels Schistosomiasis 2nd most significant disease after malaria Chronic infection with significant morbidity & mortality 4,000 years of recorded human WHO photos of children with disease (including Egyptian Schistosomiasis. It hieroglyphic for the fluke) affects 200M people in the world. Swimmer’s itch caused by a schistosome sp. that dies upon Treatment: burrowing in human skin! Praziquantel or metrifonate PHRM 203 - Anthelmintics & 5 Antifungals Trematodes (flukes): Fasciola Life cycle of M yokogawai Adult Metagonimus yokogawai Cysts ingested by eating infected Intestinal fluke of humans fresh water fish 10-15% prevalence in Japan Emerge in mammal intestines and develop into adults, shedding eggs into feces May cause systemic infection & eggs will embolize to brain, spinal cord or heart Fresh water snails infected and release larvae that encyst on fish Treatment: Praziquantel (CDC photo) PHRM 203 - Anthelmintics & 6 Antifungals Nematodes (Thread worms) Filaria: Loa loa (Loiasis) Treatment : diethylcarbamazine Pin worms: Enterobius vermicularis Treatment: OTC Pyrantel Filaria: Elephantiasis Treatment: Albendazole, diethylcarbamazine and IVERMECTIN Hookworms: N. americanus Treatment: Albendazole PHRM 203 - Anthelmintics & Antifungals 7 Nematodes: Ascarids • Humans – definitive host – Ascaris lumbricoides • Affects 1.4B people • Not Reportable in Hawaii! • Humans – aberrant host – Anisakis sp. – Toxocara canis/cati – Baylisascaris procyonis – Ascaris suum Ascaris lumbricoides PHRM 203 - Anthelmintics & 8 Antifungals Nematodes (Ascarids) Increasingly seen due to popularity of sashimi and Anisakis sp. sea food in general Common in Japan Treatment: Albendazole or Ivermectin Anisakis in cod Symptoms: severe abdominal pain within hours of ingestion, with nausea and vomiting. Symptoms may mimic Crohn’s disease. Prevent infection by cooking fish or freezing (>1 wk). PHRM 203 - Anthelmintics & 9 Antifungals Toxocara canis & T. cati Public Health • Estimate 10,000 human cases/yr in U.S. – 700 cases of Ocular Larva Migrans or OLM/yr • 5-14% seropositive in US – Accidental host, self-limiting – Corticosteroids/Albendazole • Risk factors: – Children – Pica (dirt consumption) – Dog/cat ownership PHRM 203 - Anthelmintics & 10 Antifungals Larva Migrans – Migration / presence of non-human hosted helminthic larvae within the tissues of a human – Named by location: • Visceral larva migrans (VLM) • Ocular larva migrans (OLM) • Neural larva migrans (NLM) Hookworm in a 10yr old girl’s foot PHRM 203 - Anthelmintics & 11 Antifungals Larva Migrans • VLM – Larvae lodged in liver, lungs, heart, muscle – Hook worms and whip worms are seen in skin • OLM – Inflammation and retinal scarring – Vision loss (progressive or sudden blindness) - unilateral without systemic signs – May be misdiagnosed as retinoblastoma – Loa Loa (Mansonella streptocerca, a filarial nematode) • NLM – Meningitis, encephalitis, epilepsy – Neurocysticercosis (Taenia solium, the pork tape worm) PHRM 203 - Anthelmintics & 12 Antifungals Nematodes: Filaria • Lymphatic Dracunculus medinensis, the – Elephantiasis guinea worm, must be pulled out over the course of months, • Mosquito vector there is no drug therapy. • Diethylcarbamazine for most • Subcutaneous fat – Loa Loa • Deer fly vector – River blindness (Onchocerciasis) • Black fly vector • 2nd leading cause of blindness • Merck, free Ivermectin – Guinea worms • Water fleas (drink water containing the crustacean) PHRM 203 - Anthelmintics & 13 Antifungals Wolbachia • Endosymbiotic bacteria – WIDESPREAD in insects – Filarial worms also have • Kill bacteria with doxycycline – Sterilizes and kills filarial nematodes PHRM 203 - Anthelmintics & 14 Antifungals Anthelmintics Adapted from: Focus on Nursing Pharmacology, 4th Ed. AM Karch, Lippincott, Williams and Wilkins, 2008 and Goodman and Gilman’s the Pharmacological Basis of Therapeutics 11th Ed. McGraw Hill 2006 Drug Indication Broad spectrum anthelminth. GI and tissue nematodes and Albendazole cysts of certain cestodes. Hydatid disease, (Albenza) C Neurocysticercosis, filariasis, hookworms Ivermectin Broad spectrum anthelminth, miticide and pediculocide. (Stromectol) C Threadworms, strongyloidiasis, onchocerciasis, filariasis Mebendazole Broad spectrum anthelminths. GI nematodes. Pinworms, (Vermox) roundworms, whipworms, hookworms Praziquantel B Active against cesodes and trematodes. Mainly used against (Biltricide) Schistosomes (flukes) but also against H. nana Pinworms, roundworms and hookworms. Used against Pyrantel (PinX) C trichuriasis (whip worms). - Also available OTC Diethylcarbamazine Only against specific filaria: W. bancrofti, B. malayi or B. timori (Hetrazan) C as well as loiasis. Not used for onchocerciasis. PHRM 203 - Anthelmintics & 15 Antifungals Anthelmintic Mechanisms Goodman and Gilman’s the Pharmacological Basis of Therapeutics 11th Ed. McGraw Hill 2006 Drug All PO Mechanism Albendazole Polymerization of worm tubulin into microtubules and of (Albenza) C the helminth-specific enzyme fumarate reductase Binds to glutamate-gated chloride ion channels in invertebrate Ivermectin nerve and muscle cells → ↑ permeability of cell membranes to (Stromectol) C Cl-, hyperpolarizing the nerve or muscle cell and kills the parasite. Praziquantel B Unknown may alter Ca++ uptake (leading to paralysis) or (Biltricide) adenosine uptake (blocking metabolism) Pyrantel (PinX) C Neuromuscular blocking agent (very poorly absorbed in man) Diethylcarbamazine Arachidonic acid metabolism in microfilaria (Hetrazan) C PHRM 203 - Anthelmintics & 16 Antifungals Ectoparasites & Fungi • Lice - Head, body and pubic • Ringworm - fungi Dermatophytes • Mange – mites Sarcoptes Courtesy of William D. James, MD PHRM 203 - Anthelmintics & 17 Antifungals Scabies • An arthropod – skin mite • Sarcoptes scabiei var. hominis. • Obligate parasite • Species specific (different for humans and animals) • AKA – Mange (10-20 mites) – Norwegian mites (Crusted) OBen a problem in nursing • 1,000’s to millions of mites homes PHRM 203 - Anthelmintics & 18 Antifungals Lice • Three Types – Pediculus humanus • capitus (head) – Common in school kids • humanus (body) – Common in the homeless Body louse - CDC photo (pubic) Lice cause itching and a characteristic – Pthirus pubis excoriated skin rash that looks like a = “crabs” scrape. They may also transmit – Sexually active diseases, including relapsing fever, adults typhus, and trench fever. PHRM 203 - Anthelmintics & 19 Antifungals Scabicides & Pediculicides Indication Drug Route Scabies Lice Nematodes 25% benzyl benzoate lotion* 5 % Permethrin cream B (Elimite, NIX cream, Acticin) 5% monosulfiram soap Topical (Temosol)* Crotamiton (Eurax) Piperonyl butoxide/pyrethrins (RID, Tisit, Licide) Ivermectin (Stromectol, Sklice) PO, C topical * May not be available in the US, or may be used off-label in the US PHRM 203 - Anthelmintics & 20 Antifungals Aspergillosis 2nd most common serious • Deep fungal infecHon aer Candida. – Invasive aspergillosis • Often fatal – Blastomycosis – Candidiasis Mycoses – Cryptococcosis • Bird droppings – Coccidioidomycosis • Soil • Superficial – Histoplasmosis – Candidiasis • Bird/bat droppings • Vulvovaginal – Mucormycosis • Oropharyngeal – Pseudallescheriasis • Cutaneous – Sporotrichosis – Ringworm • Rose Gardener’s D. PHRM 203 - Anthelmintics & Antifungals 21 Candida Note all the G rods • Candidiasis – Candida albicans – Normal flora in 40-80% of healthy people • Skin, mouth, vagina – Pathogenic • Δ’d immune status • Δ’d normal flora • Δ’d physiology Treatment: OTCs clotrimazole (Lotrimin) or Nystanin, Amphotericin B & fluconazole (Diflucan) PHRM 203 - Anthelmintics & 22 Antifungals Cryptococcosis • Cryptococcus neoformans – Meningitis – Pulmonary disease • Inhalation of soil/ dust • Usually no symptoms in healthy people • Potentially fatal in immunocompromised – HIV – Corticosteroids Cryptosporidiosis! PHRM 203 - Anthelmintics & 23 Antifungals Coccidioidomycosis • “Valley Fever” – Coccidioides immitis or posadasii – Flu-like illness that may become chronic pulmonary infection or systemic infection – Incidence increasing CDC Photo - Coccidioides
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