Anti trematodal drugs

Definition:
having efficiency in the treatment of trematodes. Because of the lower susceptibility to injury of immature flukes the measure of efficiency of antitrematodal drugs is measured by their efficiency against immature flukes. Includes albendazole, bithionol sulfoxide, bromsalans, carbon tetrachloride, chlorsulon, clioxanide, diamfenetide, tetrachlorodifluorethane, hexachloroethane, hexachloroparaxylene, hexachlorophene, niclofolan, nitroxynil, oxyclozanide, rafoxanide, triclabendazole..

Classifications:
1-old fasciolicides.
a-carbons tetra chloride. b-hexa chloro ethelene.

2- New fasciolicides.
a-drugs against adult worms.
-benzamidazole derivatives except "triclobendazole" for mature &immature worms. - salycilinalides. (elosantel,rafoxanide,clioxanide,oxyclioxanide). -phenole substitutes. (clorsulon,bithional,nitroxinl).

b-drugs against immature worms.

-trichabendazole: Not affect on nematodes but affect on adult and one day immature old fasciola.

-diamphemtide: Affect on immature only.

(A)Anti-nematodal drugs
(1)-carbon tetra chloride:
-used against parasites as: (Heamonchus in ruminant & Anchlestoma in dog & liver flukes in Cattle and dog & ascarse in all spp & strongylus in horse ) -used against mature(adult) fluke and ineffective against immature Fluke. -repeat every 3:4 weeks - MOA: act as fascilicide that inhibit metabolic enzymes in adult and Not effective in immature . -Toxicity symptoms: 1- drowsness. 2-muscular coordination. 3-diarrhea. 4-Hypocalcemia. 5-convulsion in late stage. 6- has hepato toxic effect. 7-cause acute and chronic liver injury.

(2)-Hexa chloroethane :
-active against liver fluke in sheep & goat. -used in adult but not in immature. -repeated 3:4 weeks. -MOA: Inhibit metabolic enzymes in mature worms. -less toxic than ccl4. -cause diarrhea and anorexia.

(3)-rafoxanide:
-active against mature(4.5:5 months) and immature(3:4) in cattle And sheep.

-active against blood sucking nematode. -MOA: Uncoupler oxidative phosphorylation by inhibition of Mitochondrial action of worm . -vermicidal effect. -given orally or s/c. -Therapeutic index: 6. -safety margin: 1:6. -Rapid absorption. -not used in cattle producing milk for human consumption may used In dry period.

(4)-closante:
-broad spectrum. -given orally. -active against mature and immature liver flukes in cattle and sheep. -as well as blood suckling nematodes (homnshus contortus). -avtive against larva of fly in nasal cavity. -affective against some tap worm. -affect on external parasites as blood suckling insects (ticks &mites). -fasciolicide -MOA: Uncoupler of oxidative phospholration. -safety margin 1:6.

(5)-oxy closanide:
-

(1)Phenothiazine

It was one of the early drugs with a fairly wide range of activity against gastro-intestinal nematodes. It was synthesised as early as 1885 but was not found to possess anthelmintic activity until 1938. Development of resistant and toxicity markedly reduced use of this drug.

(2)Piperazine It has activity against ascarid and nodular-worm infection of all species of domestic animals. Dosages of the salts of piperazine are customarily expressed in terms of the hydrate equivalent, i.e. 100 mg piperazine hydrate is equivalent to 120 mg piperazine adipate, to 125 mg piperazine citrate and to 104 mg piperazine phosphate. Anthelmintic activity of piperazine and its derivatives depends upon their anti-cholinergic action at the myoneural junction in worms, producing a neuro-muscular block. The end result is a narcotizing or paralytic effect, paralyses the worms which are then voided live in feces by normal intestinal peristaltic movement. Mature worms are more susceptible to action of piperazine than younger stages. Larval stages in host times. especially larvae that are molting. arc little affected by the drug, thus repeat treatments are generally indicated in 2 weeks for dogs and cats and 4 weeks for farm animals. General dose: Young ruminants and horse: @ 110 mg / kg and dog and cats @ 45 65 mg / kg orally. Poultry @ 32 mg / kg given each of two successive feeding or in drinking water for 2 days.

Precautions

Purgation is consequently not generally advised when piperazine is being used because if the drug is quickly voi the host, the narcotized worm may regain its motility and reestablish its position in the gut. The drug can be administered to pregnant animals and also to those animals with gastro-enteritis.

(3)Diethylcarbamazine citrate ( DEC ) It is a piperazine derivative, mostly used in hcartworm in dogs and lungworm in cattle. It is prepared as either a syrup, powder or tablet sold under several trade names. Dose: Dogs Treatment @ 22 44 mg / kg body weight 3 times daily orally for 3 successive days. Administration is postponed during pregnancy and allergic reactions are not uncommon.

(4) Benzimidazoles ( BZD ) The need for an anthelmintic with a wide range of antiparasitic action, high degree of efficacy, good margin of and versatility of administration prompted investigation of several hundred BZD compounds and the first corn was thiabendazolc ( TBZ ). Of several hundred synthesized compounds, the few selected for further development on the basis of overall safe effectiveness include albendazole, cambendazole, fenbendazole, flubendazole, mebenzole, oxfendazole, oxibert parhendazole and thiophanate. All these compounds arc now commercially produced for anthelmintic used in various countries of the world. Mode of action

The benzimedazoles act primarily by binding to nematode tubule, especially bind to dimeric tubulin, which pe the polymerization of tubulin during microtubule assembly. However, the earlier effects ascribed as inhibition of fumarate reductase activity may be secondary to the disrupt microtubules, which are essential for secretion of many enzymes. (a) Thiabendazole Thiabendazole preparations are hardly available now-a-days because of the introduction of better and safer anthelmintics. (b) Albendazole Albendazole is a broad-spectrum anthelmintic having vermicidal, ovicidal and larvicidal properties. Dose Generally, large animals @ 7.5 mg / kg body weight and @ 10 mg / kg body weight for chronic fasc single oral dose, and small animals @ 15 mg / kg body weight single dose orally. (c) Fenbendazole Dose All species of animals @ 5 mg / kg body weight single oral dose. (d) Mebendazole Mebendazole is a broad-spectrum anthelmintic and acts by virtue of its ability to inhibit glucose uptake irrevers Parasite immobilization and death occur slowly. Animals @ 7.5 mg / kg body weight single oral dose. Precautions and contraindications Animals treated should not be slaughter for human consumption within 7 days of treatment. Milk from treated animals should not be taken for human consumption within 3 days of treatment. The benzimidazoles arc free of side effects at therapeutic doses even when administered to young, sick or animals.

Embryotoxicity or teratogenicity may be developed with albendazole, parbendazole, cambendazole. (5)Probenzimidazoles It is a broad-spectrum anti-nematodal anthelmintic of ruminants and other animals including zoo animals. e.g Fat Dose : Large animals @ 6 mg / kg and dog and cat @ 10 mg / kg body weight orally for 3 days.

(6)Imidazothiazoles (a) Levamisole It is highly acceptable anti-nematodal drug because of its broad range of activity. Major advantages of levamisole are that it is effective against nematodes of the lungs and gastro-intestinal tract, has no activity against flukes, tapeworms or protozoa Levamisole hydrochloride acts by interfering selectively with carbohydrate metabolism of nematodes by inhibit:, production of succinate dehydrogenase. Inhibition of this enzyme occurs with reasonably low dose within minutes of contact. causing complete and irre muscular paralysis of worm. It is now known that levamisole modulates the immune system, that is, corrects immunologic imbalance by modifying activities of T lymphocytes and phagocytes, and thus, it has the greatest benefit in the immunologically depressed ( and often the aged ) animals or human. Dose: Ruminants @ 7.5 mg / kg and poultry @ 25 mg / kg body weight single oral dose. Precautions and contraindication There are no specific contraindication in administration of levamisole alone or with other drugs.

Salivation, muzzle foam,-coughing and vomiting may occur but these reactions will disappear in a short time after medication. It is not recommended for use during pregnancy. Treated animals should not be slaughtered for human consumption for at least 10 days. Milk from treated animals within 48 hours after treatment should not be used for human consumption. (b) Tetramisole Tetramisolc hydrochloride is a broad-spectrum anthelmintic may be used both animals and birds. Dose: I tablet / 40 kg body weight single oral dose.

(7)Tetrahydropyrimidines (a) Pyrantel pamoate It is a broad-spectrum anthelmintic and prepared for commercial use as the tartrate. The drug probably produces paralysis of worms by causing a contracture of the musculature similar to the contracture inducing action of acetylcholine. It exercises a depolarizing neuromuscular blocking effect, immobilizing the worms and causes safe expulsion. It is well tolerated and effective drug for the treatment of hookworm, roundworm and threadworm. Dose: Horse @ 6.6 mg / kg and Dog @ 5 mg / kg body weight orally. This drug should not be used in pregnant animals and very young animals. (b) Morantel citrate It is methylester analog of pyrantel and the salts of morantel have greater anthelmintic activity than the parent compound ( pyrantel ).

Morantel tartrate is marketed as an orally administered aqueous solution @ 10 mg / kg for sheep and 8.8 mg / kg for cattle.

(8)Organophosphorus compounds Organophosphorus compounds in general had their origin as pesticides and only subsequently have found use as anthelmintics. Six organophosphorus compounds may be used as anthelmintics which are dichlovos, trichlorfon, haloxon, caoumaphos, naphthalphos an dcrufomate. Dichlorvos and trichlorfon are principally used against parasitic infection in horses and dogs. Haloxon, coumaphos, naphthalophos and crufomate may be used against parasites of ruminants. These compounds act on animal parasites in inhibition of nematodal acetylcholinesterase, leading to an interference with neuromuscular transmission and consequent toxicity to the parasite. The margin of safety of organophosphorus anthelmintics is generally less than of the broad-spectrum anthelmintics. This is important not only for safety of the animals but also from the subsequent and higher than normal dosages may result in illegal residues of the drug in animals tissues and milk.

(9)Macrolid endectocides These arc the compounds with activity against with internal and external parasites especially nematodes and arthropods but they have no activity against cestodes, trematodes or protozoa. (a) Ivermectin

It is a semisynthetic derivative of avermectin that has a broad-spectrum of activity against a wide variety of arthropods and nematodes of wild and domestic animals and humans. Dose: Large animals @ 0.2 mg / kg body weight subcutaneously single injection.