antihelmintic drug

• Classification of parasitic worms:

  • Nematodes:
  • Intestinal lumen:
  • Giant round worm
  • Pin worm
  • Hook worm
  • Whip worm
  • Thread worm
  • Inhabit tissues:
  • Pork round worm
  • Filariae
  • Cestodes:
  • Beef tape worm
  • Pork tape worm
  • Fish tape worm
  • Trematodes:
  • Blood fluke
  • Liver fluke
  • Intestinal fluke
  • Lung fluke
• Nematode infestation (Intestinal):

  • Ascariasis (Giant round worm infestation):
  • Most prevalent helminthic infestation
  • Adult worm inhabit the intestine
  • Serious complications can result if worms migrate into:
  • Pancreatic duct
  • Bile duct
  • Gall bladder
  • Liver
  • Heavy infestation can lead to intestinal blockade
• Ascariasis:

  • Drug of choice:
  • Albendazole
  • Mebendazole
  • Pyrantel pamoate
  • Alternative drug:
  • Piperazine citrate
• Albendazole:

  • Chemistry: benzimidazole carbamate
  • Mechanism:
  • Inhibition of mitochondrial fumarate reductase
  • Inhibits microtubule polymerization by binding to beta-tubulin, leading to irreversibly impaired glucose uptake and immobilization of worms
  • Pharmacokinetics:
  • Erratically absorbed orally
  • Rapidly undergoes first-pass metabolism in the liver to active albendazole sulfoxide
  • Increased absorption when taken with a fatty meal
  • Distributed to tissues including Bile & CSF & enters hydatid cysts
  • Excreted through bile
  • Therapeutic uses:
• • Broad spectrum antiparasitic effective as a single dose for the treatment of various worms
  • Also effective against other parasites like E. vermicularis and T. spiralis
  • High dose used in the treatment of hydatid disease
  • Useful for neurocysticercosis
• Albendazole:

  • Adverse effects:
  • Fewer ADR when used for short-term therapy
  • With protracted therapy:
  • GI pain
  • Severe headache
  • Fever
  • Fatigue
  • Hair loss
  • Increased serum transaminase
  • Leucopenia & thrombocytopenia
• Mebendazole:

  • Mechanism: prevents uptake of glucose leading to immobilization and death
  • Drug of choice for most intestinal roundworms
  • Useful for mixed infestations
  • Pharmacokinetics: only 5-10% is absorbed & rapidly metabolized
• Mebendazole:

  • Adverse effects:
  • Transient abdominal pain & diarrhea in massive infestations
  • Embryocytotoxic & teratogenic in rats
• Pyrantel pamoate:

  • Mechanism: depolarizing neuromuscular blocker causing spastic paralysis of intestinal worms
  • Therapeutic uses: alternative to mebendazole for infestations with hookworm, pinworm, giant worms
  • Adverse effects: rare serious reactions, including NVD and CNS effects like dizziness & drowsiness
• Piperazine citrate:

  • Mechanism: paralysis of ascaris by blocking Ach at myoneural junction
  • Therapeutic uses: alternative to albendazole or mebendazole in the treatment of ascariasis
  • Adverse effects: NVD, dizziness & headache
• Enterobiasis (Pinworm infestation):

  • Serious infections are rare but may cause intense perianal itching
  • Readily transmissible; family members should be treated
  • Drugs of choice:
  • Albendazole
  • Mebendazole
  • Pyrantel pamoate
• Ancylostomiasis & Necatoriasis (Hookworm infection):

  • Common in rural areas (barefoot)
  • Adult worms attach to the intestine & suck blood leading to chronic blood loss and progressive anemia
  • Treatment options:
  • Albendazole
  • Mebendazole
  • Pyrantel pamoate
• Trichuriasis (Whipworm infestation):

  • Larva & adult worms inhabit the large intestine
  • Large worm burden may lead to rectal prolapse
  • Treatment:
  • Mebendazole (drug of choice)
  • Albendazole
• Strongyloidiasis (Threadworm infestation):

  • Larva & adult worms inhabit the small intestine
  • Drug of choice:
  • Ivermectin
  • Albendazole
  • Thiabendazole
• Thiabendazole:

  • Mechanism: inhibits fumarate reductase
  • Pharmacokinetics: rapidly absorbed & metabolized, excreted as metabolites in the urine
  • Therapeutic use: alternative drug against Strongyloidiasis & Trichinellosis
  • Adverse effects: high incidence, including GIT: ANV and neurological effects like dizziness & drowsiness
• Nematode infestation (Extraintestinal):

  • Trichinellosis (Pork roundworm infestation):
  • Adult worm resides in the intestine; Larva migrate to skeletal muscle & become encysted
  • Symptoms include GI upset, muscle pain, fever, sore throat
  • Drugs of choice: Mebendazole, Albendazole
  • Prednisolone is included to reduce inflammation during larva movement
• Wuchereriasis & Bruglasis (Lymphatic filarial infestation):

  • W. bancrofti & B. malayi invade the lymphatic system
  • Heavy infestation leads to lymphatic destruction & Elephantiasis
  • Drug of choice: Diethylcarbamazine
• Elephantiasis is caused by heavy infestation leading to lymphatic destruction
• Drug of choice for Elephantiasis is Diethylcarbamazine
• Mechanism of Diethylcarbamazine:

  • Reduces muscular activity causing the parasite to dislodge from the site of attachment
  • Alters the surface properties of parasites making them more vulnerable to attack by host defenses
• Diethylcarbamazine is readily absorbed and extensively metabolized
• Therapeutic uses of Diethylcarbamazine:

  • Drug of choice for filarial infestations
  • Destroys microfilariae of W.bancrofti, B.malayi & Loa loa
  • Kills adult females of these species
• Adverse effects of Diethylcarbamazine:

  • Minor reactions include headache, dizziness, and NV
  • More serious reactions include rash, intense itching, encephalitis, fever, tachycardia, lymphadenitis, leukocytosis, and proteinuria
  • Pre-treatment with glucocorticoids can decrease these adverse effects
• Onchocerciasis (River blindness) is caused by heavy infestation

  • Symptoms include dermatologic (nodules, pruritic dermatitis) and opthalmic (ocular lesions leading to optic neuritis, optic atrophy, blindness)
• Drug of choice for Onchocerciasis is Ivermectin

  • Mechanism of Ivermectin: disrupts nerve traffic & muscle function in the target parasite
  • Therapeutic uses include the treatment of onchocerciasis and intestinal strongyloidiasis
• Adverse effects of Ivermectin:

  • Mazotti reaction when used for onchocerciasis
  • Symptoms include pruritis, rash, fever, lymph node tenderness, bone & joint pain
  • Allergic & inflammatory response to the death of microfilariae
  • Teratogenic in mice, rats, rabbits causing cleft palate
• Taeniasis (beef & pork tapeworm) is acquired by eating undercooked beef or pork

  • Treated by Praziquantel and Niclosamide
• Diphyllobothriasis (Fish tapeworm infestation) is acquired by ingestion of undercooked fish

  • Worms are killed by Praziquantel and Niclosamide
• Niclosamide inhibits mitochondrial oxidative phosphorylation in tapeworms leading to cessation of ATP production and death

  • Therapeutic uses include being an alternative to Praziquantel in the treatment of Cestode infestations
• Niclosamide is used to treat infections caused by T. saginata (beef tapeworm), T. solium (pork tapeworm), D. latum (fish tapeworm), and H. nana (dwarf tapeworm)

  • Adverse effects are minimal due to poor absorption, with GIT side effects like ANV
• Praziquantel is absorbed by helminthes

  • At low concentration, it causes spastic paralysis and detachment of worms
  • At high concentration, it disrupts the tegument of the worm making it vulnerable to host defenses
• Therapeutic uses of Praziquantel include being active against cestodes and trematodes
• Adverse effects of Praziquantel are relatively free of toxicity, with symptoms like nausea, vomiting, and abdominal discomfort due to the liberation of helminth proteins from dead worms
• Schistosomiasis (blood fluke infestation) has acute and chronic phases

  • Praziquantel is the drug of choice for both phases
• Faciliasis (Liver fluke infestation) symptoms include anorexia, mild fever, fatigue, and itching in the region of the liver

  • Praziquantel is not effective, and Bithionol is the alternative
• Fasciolopsiasis (Intestinal fluke infestation) symptoms include disruption of bowel function leading to constipation & diarrhea

  • Massive infestation can cause bowel obstruction
  • Praziquantel is the treatment of choice