Antihelmintic or anthelmintics Drugs:
Antihelmintic or Anthelmintics are drugs that either expel (vermifuge) or kill (vermicide) infesting helminths.
Vermicidal: Antihelmintic drugs which kill the worms
Vermifuge: Antihelmintic drugs which affect the worm in such a way that help to expel the worms.
Classifications of Antihelmintic or Anthelmintics drugs:
Based on worm specific:
- For Roundworm, Hookworm, Pinworm:
- Pyrantel pamoate
- For Threadworm:
- For whipworms, Trichinella spiralis:
- For Filariasis:
- Diethylcarbamazine citrate
- For Tapeworms:
- For Hydatid worm:
Drug Therapy of worms:
- It is a benzimidazole derivative
- It is a broad spectrum of antihelmintic or anthelmintics activity
- It is poorly(˂10%) absorbed
- It has produced a nearly 100% cure rate/reduction in egg count in the roundworm, hookworm (both species), Enterobius, and Trichuris infestations, but is much less active on Strongyloides.
- Up to 75% cure rate has been reported in tapeworms, but H. nana is relatively insensitive
- Trichinella spiralis from intestines, but efficacy in killing larvae that have migrated to muscles is unsure.
- Prolonged treatment has been shown to cause regression of hydatid cyst in the liver
Mechanism of action:
The site of action: appears to be the microtubular protein ‘β-tubulin’ of the parasite.
- It binds to the tubulin of susceptible worms with high affinity and inhibits its microtubule polymerization.
- Intracellular microtubules in the cells of the worm are gradually lost.
- In addition, it blocks glucose uptake in the parasite and depletes its glycogen stores.
- The hatching of nematode eggs and their larvae is also inhibited.
- Ascaris ova are killed.
- Affected parasites are expelled in the feces
Slow acting drug: 2-3 days for parasitic clearance from the gut.
Adversely affects the ova of the pinworm and the hookworm
- Mebendazole is administered orally
- Poorly absorbed from the GI tract
- Highly plasma proteins binding nature & metabolized in the liver
- Most of the oral dose is excreted in feces (75–90%)
- The fraction absorbed is excreted mainly as inactive metabolites in urine/feces.
- The systemic toxicity of mebendazole is low because of its poor absorption.
- It is well tolerated & rarely causes gastrointestinal adverse drugs effects:-
- Diarrhea, nausea, anorexia, vomiting, and abdominal pain
- Allergic reactions, loss of hair, and granulocytopenia (at high doses)
- Embryotoxic and teratogenic in animals
- Should be avoided in pregnancy and children below one year
Highly effective against intestinal nematodes such as Roundworm, Hookworm, Whipworm, Pinworm, and mixed worm infestations.
- Tapeworm (Taenia) infestation
- Hydatid cysts of the liver: may cause bone marrow aplasia, hence Albendazole is preferred.
- More effective than albendazole in trichuriasis
Dose and administration:
- For roundworm, hookworm, whipworm:-100 mg orally twice a day for 3 consecutive days. It does not require fasting or purging, is well-tolerated, & is comparatively cheap.
- Pinworm (Enterobius): 100 mg single dose, but repeatedly after 2–3 weeks to kill the ova that have developed later. Strictly hygienic measures & simultaneous treatment of all children in the family or class are advocated to cut down autoinfection & person-to-person infection or transmission.
This holds true of enterobiasis, disregarding the drug used.
- Trichinosis: 200 mg BD for 4 days; but it is a less effective drug than albendazole.
- Hydatid disease: 200–400 mg BD or TDS for 3–4 weeks; but is a less effective drug than albendazole
- It is a benzimidazole derivative.
- It is a broad spectrum of anthelmintics or antihelmintic activity and excellent tolerability of its predecessor.
- It has the advantage of single-dose administration in many common intestinal worm infestations and is cost-effective.
- It also has larvicidal actions in hydatid disease, roundworm, and hookworm
- Ovicidal properties in roundworm, hookworm, and whipworm (Trichuris)
The mechanism of action similar to Mebendazole.
- It is given orally
- Better bioavailability than mebendazole
- It is enhanced when the drug is taken with a fatty meal (this may help in treating neurocysticercosis and hydatid disease).
- The fraction absorbed is converted by the first-pass metabolism to its sulfoxide metabolites which have potent anthelmintic action.
- Will distributed in the tissues, bile, CSF, and hydatid cyst.
- T1/2: 8-12 hours
- Mild, mainly GI disturbances
- Few patients have felt dizziness
- Prolonged use, as in hydatid or in cysticercosis, has caused headache, fever, alopecia, jaundice, liver damage, bone marrow depression, and neutropenia.
- Ascaris, hookworm, Enterobius, and Trichuris: a single dose of a drug is 400 mg for in case of adults and children above 2 yrs, 200 mg for 1–2 yr age. Three-day treatment may be needed in heavy trichuriasis conditions.
- Weak microfilaricidal
- Tapeworms and strongyloidiasis: dose is 400 mg daily for 3 consecutive days. The efficacy in strongyloidiasis is low, and it is the second choice drug to ivermectin.
- Neurocysticercosis: choice for the treatment of neurocysticercosis(Usually 8–15 days course of 400 mg BD (15 mg/kg/day) is employed.
- Cutaneous larva migrans: Albendazole is 400 mg daily for three days
- Hydatid disease: 400 mg BD for four weeks, repeat after two weeks if required, up to 3 courses treatment.
It is the preferred treatment given before and after surgery as well as inoperable cases.
- Filariasis: Added to diethylcarbamazine (DEC) or ivermectin, albendazole has adjuvant value in treating lymphatic filariasis
- Drug of choice because of a short course
- Less toxicity than praziquantel
- Better penetration into CSF and cost-effective
- Given 400mg bid for 21 days
- Glucocorticoids are started prior to albendazole to reduce the intensity of the inflammatory reaction to the dead parasites.
- Efficacy against Ascaris, Enterobius, and Ancylostoma is high and equivalent to that of mebendazole.
- Lower cure rates of about 60 percent have been obtained in the case of Necator infestation.
- It is less active against Strongyloides conditions and inactive against Trichuris and other worms.
Mechanism of action:
- Pyrantel causes activation of nicotinic cholinergic receptors in the intestinal as well as extra-intestinal worms resulting in persistent depolarization → slowly developing contracture and spastic paralysis.
- An anticholinesterase action has also been demonstrated.
- Only 10–15 percent of an oral dose of pyrantel pamoate is absorbed in the body: this is partly or partially metabolized and excreted in the urine.
- Mild and include GI disturbances
- Abdominal pain
- Skin rashes
- Roundworm, Pinworm, Hookworm infestation
- It can be used during pregnancy and in children below 2 years
Mechanism of action:
- Acts as a GABA agonist and causes hyperpolarization of Ascaris muscle resulting in flaccid paralysis of the worms which are then easily expelled by peristaltic movements. (N.B. Opening of Cl¯ channels causes relaxation and depresses responsiveness to contractile action of ACh= Hperpolariztion)
- This eliminates the danger of worm migration
- Wide margin of safety, common:
- Nausea, vomiting, diarrhea, and urticarial
- Rare :
- Muscular incoordination, hypotonia, ataxia
- Worm wabble: the dropping of objects, clumsiness, and gait abnormalities
- The drug is safe during pregnancy
- It causes sustained contracture of the somatic muscle of the worm by an irreversible, non-competitive depolarization type of neuromuscular block
- Interference with carbohydrate metabolism
- Nausea, vomiting, abdominal pain, diarrhea, giddiness, and drowsiness
- Not active against larvae and hence follow-up re-evaluation of treated patients.