Antitrematodal Drugs:
- These are agents used to kill or prevent fluke infections in animals
Classification:
On the basis of chemical structure, they are broadly divided into following groups:
- Substituted phenols: Nitroxinil, Hexachlorophane, Niclofolon and Biothionol
- Salicylanilides: Closantel, Rafoxanide, oxyclozanide, brotianide, Niclosamide and Bromosalans
- Aromatic amides: Diamfenetide
- Sulphonamides: Clorsulon
- Halogenated hydrocarbons: Carbon tetrachloride, hexachloroethane, tetrachlorodifluoroethane and hexachloroparaxylene
- Benzimidazole and pro-benzimidazole: Albendazole, Triclabendazole, Luxabendazole, Fenbendazole and Netobimin
- Isoquinolones: Praziquantel
- Miscellaneous drugs: Niridazole and Stibophen
# Substituted phenols:
Nitroxinil:
- It is injectable fasciolicide
- It is sparingly soluble in water and moderately soluble in most organic solvents
Mechanism of action:
They block/uncouple oxidative phosphorylation of mitochondria in parasite
Depletion of ATP of parasites
Parasite gets killed and expel from body
Antihelmintic spectrum:
- Active against Fasciola hepatica and sucking nematodes
- Also active against gapeworms (Syngamus) in game birds
- It has low efficacy against Paramphistomum in sheep and cattle and immature flukes in liver parenchyma.
Pharmacokinetics:
- It is not well absorbed orally because they rapidly metabolize and inactivated in rumen.
- After SC injection, it is rapidly and completely absorbed
- Peak plasma concentration achieved in 30-60 minutes after injection
- It has high plasma albumin binding
- Slowly eliminated from body via faeces and urine. It is also excreted in milk.
Side effects/Adverse effects:
- Well tolerated at recommended dosages with 4 fold safety margin.
- Side effects are observed in severely dehydrated, poorly nourished or with severe parasite infection
- GI disturbances (loss of appetite and diarrhoea) and transitory inflammatory reactions at injection site
- High doses produce blindness, hyperthermia, hyperventilation, convulsion, tachycardia and ultimately death.
Contraindications and precautions:
- In weak, emaciated and poorly nourished animals
- In lactating cows
Clinical use:
- For mature Fasciola and some GI roundworms in ruminants
- Against gapeworm in game birds
- For immature flukes at high doses.
Dose:
Cattle and sheep: 10 mg/kg, SC
Game birds: 24 mg/kg, PO, in drinking water
# Salicylanilides:
Closantel:
- It is salicylanilides antihelmintic
Mechanism of action:
They block/uncouple oxidative phosphorylation of mitochondria in parasite
Depletion of ATP of parasites
Parasite gets killed and expel from body
Antihelmintic spectrum:
- Broad-spectrum antihelmintics
- Active against adult and juvenile Fasciola flukes, blood sucking nematodes and some tapeworm
- Also active against certain arthropods like manges mites, ticks and parasitic larvae of flies.
- No activity against Paramphistomum flukes
Pharmacokinetics:
- Well absorbed after oral administration
- Peak plasma concentration achieved in 24 hrs
- Extensively bound to plasma proteins, mainly to albumin
- Slowly excreted in faeces (80%) and also in urine
Side effects/Adverse effects:
- Well tolerated at recommended dosages
- High dosages produces toxicity characteristics of uncoupling of oxidative phosphorylation like hyperthermia, hyperventilation, tachycardia and convulsion.
Clinical use:
- Primarily used as flukicide in sheep and cattle
- Also used to treat blood sucking nematodes and susceptible tapeworms
Dose:
Cattle and sheep: 5 mg/kg, SC
10mg/kg, PO
Oxyclozanide:
- Oral salicylanilides fasciolicide
- Mainly effective against adult flukes
- Distributed to liver, kidneys and intestine and primarily excreted in bile
- Sheep tolerate 4 times recommended dose of oxyclozanide with no adverse effects
- It is used in combination with other antihelmintics such as levamisole for broad-spectrum antihelmintic treatment
Dose:
Cattle and sheep: 10-15 mg/kg, PO
Aromatic amines:
Diamfenetide:
- It is an aromatic amide antitrematodal drug
Mechanism of action:
- Exact mechanism of diamfenetide is not known clearly
- It causes vacuolation of flukes tegument and induce paralysis which are then expelled from the body
- They are rapidly metabolized to active amine metabolite and destroyed in liver itself. So, it is effective in liver only where immature flukes lie.
Antihelmintic spectrum:
- They are highly effective against very young Fasciola flukes in sheep
- No activity against flukes in cattle
Pharmacokinetics:
- Well absorbed after oral administration and distributed throughout the body
- Rapidly deacylated in liver to form corresponding amine, which is active and responsible for fasciolicidal action.
- Slowly excreted from body
Side effects/Adverse effects:
- Safe at recommended dosages
- High dose produces temporary impairment of vision and loss of wool
Contraindications and precautions:
- In sheep producing milk for human consumption
Clinical use:
- Against young flukes in sheep
- Combined with rafoxanide to provide prophylaxis against fascioliosis
Dose:
Sheep: 100 mg/kg, PO
Sulphonamides:
Clorsulon:
- It is benzene sulphonamide
Mechanism of action:
Clorsulon inhibit 3-phosphoglycerate kinase and phosphoglycomutase enzymes in EMP in susceptible flukes
Deprivation of metabolic energy
Parasite gets killed and expel through body
Antihelmintic spectrum:
- They are highly effective against F.hepatica in both sheep and cattle
- Younger flukes are affected at high dosages
- Less active against Fasciola magna and inactive against paramphistomum
Pharmacokinetics:
- Rapidly absorbed after oral administration
- Peak plasma concentration occurs at 4 hours and peak plasma concentration achieved in 4-12 hrs after dosing.
- Extensively bound to plasma protein (~75%) and remainder (~25%) is bound to red cells.
Side effects/Adverse effects:
- Safe in pregnant and breeding animals
- No embryotoxic, mutagenic or carcinogenic effect
Clinical uses:
- It is used as flukicide in cattle and sheep
- Combined with ivermectin in SC injectable formulation for treatment of Fasciola and nematode infection in cattle, simultaneously
Dose:
Cattle and sheep: 7 mg/kg, PO
Cattle: 4 mg/kg, SC
2 mg/kg Clorsulon + 0.1 mg/kg, ivermectin, SC
Halogenated hydrocarbons:
Carbon tetrachloride:
- It was first drug to be introduced for treatment of fascioliosis
- Volatile, clear, non-inflammable liquid
Mechanism of action:
- Exact mechanism is not known clearly
- Acts by formation of toxic metabolites which are lethal to liver flukes
- Interference in cholesterol biosynthesis and accumulation of toxic methyl sterols in target parasites is probable mode of action.
Antihelmintic spectrum:
- Active against adult Fasciola flukes in sheep, but doesnot affect immature flukes in liver
- Also active against some blood sucking nematodes including Ancylostoma in dogs and cats and Haemonchus and Bunostomum in cattle and sheep.
Pharmacokinetics:
- Absorbed slowly from intestine, after oral administration
- After absorption, it is metabolized to active metabolites which are excreted through bile and urine
- Elimination occurs through lungs also
Side effects/Adverse effects:
- It has narrow margin of safety
- It produces both acute and delayed toxicity. Acute toxicity include CNS depression, diarrhoea, incoordination, renal damage leading to anuria and azotemia, circulatory collapse and death.
- Delayed toxicity include liver damage, kidney damage and visual disturbances.
Contraindications and precautions:
- In patients with pre-existing hepatic or renal insufficiency
- Not recommended in horses, swine and cats due to high toxicity
Clinical use:
- It is widely used to treat fascioliosis in sheep
Dose:
Sheep: upto 4 ml, PO