Chemotherapy of Helminthic Infections

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

Anthelmintics
Anti-helmintics
Anti-helminthics

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 2 chemotherapy is sustained unless reunfected.

Roundworms

Hookworms

Whipworms

Pinworms

Nematodes
Filariasis Guinea worm

Trematodes

1. Albendazole 2. Diethylcaba mazine 3. Ivermectin 4. Praziquintal Cestodes

Tape worm
[Beef, pork, fish, dwarf]

Neurocysticercosis

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]
Not used Sometimes DOC

Mechanism of antihelminthic action: Inhibits microtubule synthesis. Glucose transport

Albendazole
Broad-spectrum oral antihelminthic, Pinworm Hookworm, Ascariasis, Trichuriasis, Microfilaria Hydatid disease and cysticercosis.

AlbendazoleAdministration
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 23 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 100mg BDx3days. No bowel preparation Hook Pin

Enterobius: 100 mg single-Repeat after2 weeks, hygiene Preferred in multiple infections Disadvantage: Multiple dose

Thiabendazole: Toxic[absorbed]
Only when others fail

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 23 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 infectionDEC+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 coordination, 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 Expensive
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Praziquantel 4 weeks] Lower cure rates[60% Glucocorticoids & antiepileptics reduced BA

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

 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

Bephenium hydroxynapthoate

Levamisole
Ascariasis & ankylostomiasis Larvicidal against Strongyloides Sustained contracture of somatic muscles of the worm by an irreversible noncompetitive depolarization type of neuromuscular block Also has immunostimulant property

Roundworms

Hookworms

Whipworms

Pinworms

Nematodes
Filariasis Guinea worm

Metronidazole

Trematodes

1. Albendazole 2. Diethylcarba mazine 3. Ivermectin 4. Praziquintal Cestodes

5. 6. 7. 8.
Neurocysticercosis

Pyrantel Niclosamide Piperazine Levamisole & Tetramisole

Tape worm
[Beef, pork, fish, dwarf]

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