OTHER ENDOPARASITICIDES

Question 1

Clorsulon (aminobenzene disulphonamide derivative)

Answer 1

• Inhibits enzymes of the glycolytic pathway in liver flukes, (cellular energy production is disrupted).
• In plasma is bounded to proteins.
• Safety margin is wide (TI=20).
• Not licensed for use in lactating dairy cows.
• Sheep PO suspension for infections with (mainly) adult liver flukes.
• Cattle SC injection in combination with Ivermectin.

Question 2

Bunamidine (salts)

Answer 2

anticestodal naphtamidine compounds.

• Used in small animals, leads to digestion of tapeworms in the gut of the host, due to an inhibition of glucose uptake of worms.
• Most effective if given after fasting. - It is absorbed and metabolized in the liver.
• Vomiting and mild diarrhoea may be seen, and exercise or excitement should be avoided in dogs soon after administration

Question 3

Emodepside

Answer 3

Is synthesised by attaching a morpholine ring to a metabolite of Mycelia sterile (fungus inhabiting leaves of Camellia japonica).

Mechanism of action
Inhibitory effect on synaptic transmission, by binding to a group of G-protein coupled receptors called latrophilins=>activates the channel=> K+ efflux, hyperpolarization & subsequent inhibition of excitatory neurotransmitter effect of Ach, inhibiting muscle in the parasitic nematodes (flaccid paralysis) & inhibiting locomotive & pharyngeal pumping functions, furthermore inhibition of egg laying.

Therapeutic use

• Is effective against a number of gastrointestinal nematodes, roundwoms, hookworms
• Licensed for use in combination with Praziquantel in Fe for topical application (spot on), in Ca for oral application (tablets)
• With Toltrazuril (solution) for puppies

Safety
Adverse reactions are rare (licking, excessive grooming, scratching treatment site, salivation, lethargy, alopecia, agitation/nervousness, vomiting, diarrhoea, eye + respiratory irritation, shaking/tremors). All adverse reactions are self-limiting.

Question 4

MELARSOMINE

Answer 4

• Organic arsenical compound
• PD Adulticide, - microfilarias are not sensitive – Mechanism: alterations in glucose uptake and metabolism, inhibition of glutathione reductase
• PK good tissue distribution, crosses BBB. Half-life in dog 3 h. Incomplete metabolism in liver, excretion in urine and bile.
• TOX low therapeutic index: – 3-times overdose - serious pulmonary oedema - lethal. – Slight overdose – serious GI symptoms (emesis, diarrhoea) bradycardia, tremor and severe depression.
• Dose 2.5 mg/kg bw IM (see schedule of therapy); – deeply into the lumbar (epaxial) muscles in the third to fifth lumbar vertebral region (L3-L5)

Question 5

Amino-acetonitrile derivatives, monepantel (Zolvix®)

Answer 5

• Mechanism: agonist on nicotinic receptors of worms (Hco-MPTL-1 unit – no cross-resistance exists).
• Spectrum: relatively narrow, GI nematodes (including hypobiotic larvae).
• Resistance: Originally active against nematodes that are resistant to other anthelmintics. Resistance was detected few years following its introduction. (reduced susceptibility =>full resistance)
• Pharmacokinetics: Absorption from GI is good. Rapid metabolization to sulfoxide and sulfone metabolites. Excretion with faeces, via bile. Cmax 24 hours, t1/2 5 days.
• Toxicity: 10 times overdosing is well tolerated by sheep
• Dose: 2.5 mg/ttkg p.o. once (repeat in case of reinfection)