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Home , Anisakis, Ascaris lumbricoides, Ascaris suum, Baylisascaris, Baylisascaris procyonis, Dracunculus medinensis

Micro 5 Antiparasiticals , Pediculicides, Miticides, Antifungals

PHRM 203 Allison Beale Helminths

The parasitic • Phylum/Class – “Thread” worms • Class Cestodes • “Round” worms – “Tape” worms – lumbricoides – sp. • nana • “Whip” worms • - Neurocysticercosis = most – common brain parasite • “Filarial” worms • - – Hydatid d. – bancrofti • “Spiral” worms • Class Trematodes – Trichinela spiralis – “Flukes” • “Hook” worms • >20K (Strongyles) • versus tissue – americanus – • “Pin” worms – Fascioliasis – Enterobius vermicularis

Phylum Platyhelminths

PHRM 203 - Anthelmintics & 2 Antifungals % World Population with Helminth

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= ; C = Cestode; T=Trematode PHRM 203 - Anthelmintics & 3 Antifungals Cestodes (tape worms)

Hymenolepis Echinococcus nana granulosis “” tape tape worm

Proglod – Treatment: , 80K ea. or

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 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 ! Praziquantel or metrifonate PHRM 203 - Anthelmintics & 5 Antifungals Trematodes (flukes): Fasciola

Life cycle of M yokogawai Adult yokogawai ingested by eating infected Intestinal fluke of fresh water fish 10-15% prevalence in Japan Emerge in mammal intestines and develop into adults, shedding eggs into May cause systemic infection & eggs will embolize to brain, spinal cord or Fresh water snails infected and release larvae that encyst on fish

Treatment: Praziquantel (CDC photo)

PHRM 203 - Anthelmintics & 6 Antifungals Nematodes (Thread worms)

Filaria: (Loiasis)

Treatment :

Pin worms: Enterobius vermicularis Treatment: OTC

Filaria:

Treatment: Albendazole, diethylcarbamazine and

Hookworms: N. americanus Treatment: Albendazole

PHRM 203 - Anthelmintics & Antifungals 7 Nematodes: Ascarids

• Humans – definitive – • Affects 1.4B people • Not Reportable in Hawaii! • Humans – aberrant host – Anisakis sp. – /cati – procyonis – Ascaris lumbricoides

PHRM 203 - Anthelmintics & 8 Antifungals Nematodes (Ascarids) Increasingly seen due to Anisakis sp. popularity of and sea in general Common in Japan Treatment: Albendazole or Ivermectin

Anisakis in

Symptoms: severe 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 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: • (VLM) • Ocular larva migrans (OLM) • Neural larva migrans (NLM) in a 10yr old girl’s foot

PHRM 203 - Anthelmintics & 11 Antifungals Larva Migrans

• VLM – Larvae lodged in , , 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 ( streptocerca, a filarial nematode) • NLM – , encephalitis, epilepsy – Neurocysticercosis (Taenia solium, the pork tape worm)

PHRM 203 - Anthelmintics & 12 Antifungals Nematodes: Filaria

• Lymphatic medinensis, the – Elephantiasis guinea worm, must be pulled out over the course of months, • there is no drug therapy. • Diethylcarbamazine for most • Subcutaneous fat – Loa Loa • vector – River blindness () • Black fly vector • 2nd leading cause of blindness • Merck, free Ivermectin – Guinea worms • Water fleas (drink water containing the )

PHRM 203 - Anthelmintics & 13 Antifungals

• 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, , Ivermectin Broad spectrum anthelminth, miticide and pediculocide. (Stromectol) C Threadworms, , 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 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 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 ) Pyrantel (PinX) C Neuromuscular blocking agent (very poorly absorbed in man) Diethylcarbamazine  Arachidonic acid metabolism in (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 – skin mite • Sarcoptes scabiei var. hominis. • Obligate parasite • Species specific (different for humans and ) • AKA – Mange (10-20 mites)

– Norwegian mites (Crusted) Oen 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 , 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 infecon 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 spherule with Cryptosporidiosis & Cryptococcosis! endospores in

PHRM 203 - Anthelmintics & 24 Antifungals Ringworm

• Several different species of fungi, not worms – Epidermophyton – Microsporum – Trichophyton • Grow only in keratinized tissue – Stops at living tissue Tinea corpus – skin – Infects the hair shaft Tinea cruris – groin • Can live in humans, animals, and soil Tinea pedis – foot/toes • Sometimes a zoonotic disease Onychomycosis - nailbed

PHRM 203 - Anthelmintics & 25 Antifungals Ringworm:

• Direct – Skin-to-skin contact with an infected person or pet • Indirect/Fomite – Infected individual touched object – Hats, combs, brushes, bed linens, stuffed animals, telephones, gym mats, shower stalls, etc. • Rarely, by contact with soil

PHRM 203 - Anthelmintics & 26 Antifungals Ringworm: Treatment

• Ringworm usually responds well to self-care within 4 weeks without having to see a doctor – Keep skin clean and dry – Over-the-counter antifungal or drying powders, lotions, or creams – Wash sheets and nightclothes every day while infected. • Antifungals – Prescription and OTC – Miconazole, clotrimazole, etc.

PHRM 203 - Anthelmintics & 27 Antifungals Systemic Antifungals

Drug Indication Amphotericin B Aspergillosis, Blastomycosis, Candidiasis, (Amphotec, Coccidiodomycosis, Cryptococcosis, Histoplasmosis, Fungizone) B Mucormycosis, Sporotrichosis Capsofungin acetate Candidiasis, invasive aspergillosis in patients refractory to (Cancidas) other treatements 5-Fluorocytosine Cryptococcosis, candidiasis (Flucytosine) Fluconazole Systemic, vulvovaginal and oropharyngeal Candidiasis, (Diflucan)C Coccidioidomycosis. Cryptococcal meningitis. Griseofulvin Tinea sp. (Ringworm)

Terbinafine (Lamisil) Tinea sp. (Ringworm)

PHRM 203 - Anthelmintics & 28 Antifungals Amphotericin B • Indications – ONLY potentially life threatening fungal inf • ADRs – Administer IV slowly under close watch • Fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, and tachypnea are common 1 to 3 hours after starting IV • Inject no > 1.5 mg/kg

¨ Only for life-threatening fungal infections ¨ May cause fatal cardio or cardiopulmonary arrest

PHRM 203 - Anthelmintics & 29 Antifungals Fluconazole (Diflucan) • ADRs Mostly for serious Candida infections – Liver failure, SJS, , arrhythmias – LOTS (& LOTS) of drug interactions PO, IV Oral hypoglycemics Terfenadine Coumarin-type anticoagulants Cisapride Phenytoin Astemizole Cyclosporine Rifabutin Rifampin Tacrolimus Theophylline Short-term benzodiazepines

POTENT $ P450 D

PHRM 203 - Anthelmintics & 30 Antifungals Topical Antifungals

Drug Indication Vulvovaginal, Oropharyngeal and Cutaneous candidiasis; Clotrimazole (Lotrimin) Tinea sp. (Ringworm) B also OTC Topical (creams, spray, soluon, lozenges/troches)

Ketoconazole Cutaneous candidiasis, Tinea sp. (Ringworm)

Nystatin Vulvovaginal, Oropharyngeal and Cutaneous candidiasis

Vulvovaginal and Cutaneous candidiasis; Tinea sp. Miconazole (Ringworm)

Terbinafine (Lamisil) Onychomycosis of the toenail or fingernail due to Tinea sp.

Tolnaftate Tinea sp. (Ringworm)

PHRM 203 - Anthelmintics & 31 Antifungals