Dr.U.P.Rathnakar MD.DIH.PGDHM 1

Chemotherapy of Helminthic Infections

• Metazoa -roundworms (nematodes) and two types of flatworms-flukes (trematodes) and tapeworms (cestodes).

• Immature forms invade humans via the skin or GI tract and evolve into - adult worms with characteristic tissue distributions.

• Cannot complete their life cycle [Except Strongyloides and Echinococcus,] and multiply

• Infection intensity, which itself determines the morbidity caused by infection.

• Reduction in the number of adult organisms by chemotherapy is sustained unless reunfected.

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Anthelmintics Anti-helmintics

Anti-helminthics

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Roundworms Hookworms Whipworms Pinworms

Filariasis Guinea worm

Tape worm [Beef, pork, fish, dwarf]

Nematodes

Neurocysticercosis

Cestodes

Trematodes

1. Albendazole

2. Diethylcaba

mazine

3. Ivermectin

4. Praziquintal

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Anthelmintics

Anthelmintics are drugs

That act either locally to expel worms from the gastrointestinal tract or

Systemically to eradicate adult helminths or developmental forms that invade organs and tissues

• Benzimidazoles Thiabendazole. mebendazole & albendazole

• Pyrantel pamoate

• Piperazine

• Levamisole

• Diethylcarbamazine citrate

• Ivermectin

• Niclosamide

• Praziquantal

• Bephenium hydroxynapthoate

• Metrifonate, Oxamniquine, Doxycycline

Benzimidazoles

[Thiabendazole. mebendazole & albendazole]

• Mechanism of antihelminthic action:

Inhibits microtubule synthesis.

Glucose transport

Not used Sometimes DOC

Albendazole

• Broad-spectrum oral antihelminthic,

• Pinworm

• Hookworm,

• Ascariasis,

• Trichuriasis,

• Microfilaria

• Hydatid disease and cysticercosis.

Albendazole-

Administration

• Administered on an empty stomach when used against intraluminal parasites

• With fatty meal when used against tissue parasites.

Albendazole-

• ASCARIASIS, TRICHURIASIS, AND HOOKWORM AND PINWORM

• Adults and children older than 2 years -Ascariasis and hookworm infections, -single dose of 400 mg orally

• Repeated for 2–3 days for heavy ascariasis infections and in 2 weeks for pinworm infections

Albendazole

• HYDATID DISEASE

• Medical therapy and adjunct to surgical removal or aspiration of cysts

• More active against Echinococcus granulosus than against E multilocularis

• 400 mg twice daily with meals for 1 month

Albendazole-Clinical Uses….

• NEUROCYSTICERCOSIS

• Albendazole -drug of choice over praziquantel

• Corticosteroids -given with the antihelminthic drug to decrease inflammation caused by dying organisms

• 400mg bdx21 days • Antihelminthic therapy may not superior to therapy with corticosteroids

alone and may exacerbate neurologic disease

Mebendazole

• MOA: same as earlier

• Round

• Hook

• Pin

• Enterobius: 100 mg single-Repeat after2 weeks, hygiene

• Preferred in multiple infections

• Disadvantage: Multiple dose

• Thiabendazole: Toxic[absorbed]

• Only when others fail

100mg BDx3days. No bowel preparation

Benzimidazole-Toxicity

[Thiabendazole-Mebendazole-Albendazole]

• Nausea, vomiting, loss of appetite, headache, giddiness • Itching, abdominal pain, diarrhoea • Neurological symptoms, Impairs

alertness • Bradycardia, hypotension & liver

damage • Hypersensitivity reactions • Avoid in renal & hepatic disease • CI in pregnancy • Expulsion of Ascaris from mouth or nose

Pyrantel Pamoate

• Antihelmintic Action

– Depolarizing neuromuscular blocking agent – Persistent activation of nicotinic acetylcholine

receptors, which results in spastic paralysis of the worm

– Also inhibits cholinesterases

Round worm, hook worm, pin worm

10mg.kg

DIETHYLCARBAMAZINE CITRATE

[DEC]

• DEC- Drug of choice - filariasis,

loiasis, and tropical eosinophilia

• MOA- Immobilizes microfilariae and alters their surface structure [hyperpolarization], displacing them from tissues and making them more susceptible to destruction by host defense mechanisms.

• Against adult worms is unknown.

DEC-CLINICAL USES

• Taken after meals

• Wuchereria bancrofti, Brugia malayi, Brugia timori, and Loa loa

• Efficacy and lack of serious toxicity

• 50 mg -day 1,

• 50 mg TID-day 2,

• 100 mg TID - day 3,

• 2 mg/kg -TID/ day –To complete the 2–3 week

• Chemoprophylaxis (Yearly with Albendazole)

DEC-Other uses

• Tropical eosinophilia, orally 2 mg/kg TID daily - 7 days

• Mass treatment to reduce the prevalence of W bancrofti infection- DEC+Ivermectin+Albendazole

DEC-Toxicity

• Mild and transient, include headache, malaise, anorexia, weakness, nausea, vomiting, and dizziness

• Release of proteins from dying microfilariae[third and twelfth days of treatment]

• If lymphangitis-Delay tt to quiscent period

• Severity varies in different species

• Heavy loads of microfilariae- Eosinophilia, Proteinuria , retinal hemorrhages, encephalopathy

• Antihistaminics & Steroids for reactions

Mazzotti reaction

[DEC]

• Patients with onchocerciasis:

– Typically occurs within a few hours after the first dose

– Intense itching, enlargement and tenderness of the lymph nodes, and papular rash, fever, tachycardia, arthralgias, and headache.

– This reaction persists for 3 to 7 days and then subsides, after which high doses sometimes can be tolerated

Niclosamide

• Second-line drug for the treatment of most tapeworm infections,

• Antihelminthic Actions:Adult worms (but not ova) killed, -inhibition of oxidative phosphorylation or stimulation of ATPase activity

• Clinical Uses

• The adult dose of niclosamide is 2 g once, given in the morning on an empty stomach.

• The tablets must be chewed thoroughly and then swallowed with water

• May be preferred if occult neurocysticercosis is suspected [is not

absorbed]

Niclosamide- ADE

• Transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort.

• Alcohol should be avoided on the day of treatment and for 1 day afterward.

• Safety not established in pregnancy or for children younger than 2 years of age.

PIPERAZINE

• Piperazine is an alternative for the treatment of ascariasis,

• Piperazine-paralysis of ascaris by blocking acetylcholine at the myoneural junction;

• GABA-receptor agonist • ↑ chloride ion conductance hyperpolarization & reduced

excitability muscle relaxation and flaccid paralysis

• Unable to maintain their position in the host, live worms are expelled by normal peristalsis.

• 75mg/kg for 2 days

• Not be given to women during pregnancy,

• Not to patients with impaired renal or hepatic function,

• Not to those with a history of epilepsy or chronic neurologic disease.

PIPERAZINE- A/E:

• Nausea, vomiting, diarrhoea,

urticaria

• Rarely neurotoxic effects:

vertigo, muscular in co-

ordination, hypotonia, cerebellar

ataxia, paraesthesiae, blurring of

vision & convulsions

Praziquantel

• Cestodes and trematodes

[NOT nematodes]

• Causes↑ muscular activity, leakage of

intracellular calcium from cellular membranes contraction and spastic paralysis.

• Affected worms detach from blood vessel walls, rapid shift from the mesenteric veins to the liver.

• Active against adult, larval & juvenile stages

Clinical Uses-Praziquantel

• Tablets are taken with liquid after a meal;

• Swallowed without chewing because their bitter taste can induce retching and vomiting.

• Praziquantel is the drug of choice for all forms of schistosomiasis.

• ALSO USED IN: CLONORCHIASIS, OPISTHORCHIASIS, AND PARAGONIMIASIS, TAENIASIS AND DIPHYLLOBOTHRIASIS, NEUROCYSTICERCOSIS, H NANA, HYDATID DISEASE

Praziquantel

• Abdominal discomfort, diarrhea, headache, dizziness, and drowsiness may occur; transient and dose-related

• Indirect effects such as fever, pruritus, urticaria, rashes, arthralgia, and myalgia: related to parasite burden.

• In neurocysticercosis, inflammatory reactions may produce meningismus, seizures, mental changes, and cerebrospinal fluid pleocytosis. – delayed in onset, – last 2 to 3 days – respond to appropriate symptomatic therapy such

as analgesics and anticonvulsants

Neurocysticercosis

Albendazole

• Short course[2weeks]

• Higher cure rates[90%]

• Glucocorticoids enhance absorption & antiepileptics do not affect BA

• Not expensive

Praziquantel

• 4 weeks]

• Lower cure rates[60%

• Glucocorticoids & antiepileptics reduced BA

• Expensive

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Metrifonate

• Organophosphorus compound used first as an

insecticide and later as an anthelmintic,

especially for treatment of schistosomiasis

haematobium

• Prodrug; it is converted -a potent cholinesterase

inhibitor

• Clinically only against infections with S.

haematobium

Oxamniquine

• Second-choice drug to praziquantel for the

treatment of schistosomiasis.

• S. haematobium and S. japonicum are virtually

unaffected by therapeutic doses.

• Low incidence of mild side effects and with high

efficacy after a single oral dose

Bephenium

hydroxynapthoate • Round worms and hookworms of the

species Ancylostoma duodenale

• Contracture of parasite muscles -expulsion of the parasites by peristaltic movements

• Slightly absorbed from gut

• Nausea, vomiting & diarrhoea, bitter taste

• Safe in anaemic, elderly &pregnant individuals

Levamisole • Ascariasis & ankylostomiasis

• Larvicidal against Strongyloides

• Sustained contracture of somatic muscles of the worm by an irreversible non-competitive depolarization type of neuromuscular block

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• Also has immunostimulant property

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Roundworms Hookworms Whipworms Pinworms

Filariasis Guinea worm

Tape worm [Beef, pork, fish, dwarf]

Nematodes

Neurocysticercosis

Cestodes

Trematodes 1. Albendazole

2. Diethylcarba

mazine

3. Ivermectin

4. Praziquintal 5. Pyrantel

6. Niclosamide

7. Piperazine

8. Levamisole &

Tetramisole

Metronidazole