Avermectin (2)

AVERMECTINSBy Mariwan A. Omer & Pavel O. Qader 3rd year student College of Veterinary medicine

OBJECTIVES Introduction about Helminth.

Anthelmentic drug Avermectins.

Describe the mechanism of action .

Toxicity and side-effects.

HELMINTH

Helminth infections of humans are clearly of considerable importance

They are of even greater relative importance in our domestic animals

herbivores are an easy target for many nematode species.

PARASITIC HELMINTHES

‘Helminth’ is a general term meaning ‘worm’

Nemat-helminths are round-worms

Platy-helminths are flat-worms

Cestoda (tapeworms)

Trematoda (flukes)

ECONOMIC IMPACT OF HELMINTH INFECTIONS

1. Direct tissue damage and decreased functioning of the affected organs.

2. Diversion of energy and protein resources of the host from production towards defense and immune mechanisms.

3. Reduced feed intake.

NOW WHO CAN FIGHT WITH THEM? Simplest answer ((Anthelmintic agents))

AVERMECTINS

The avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties, These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. 

HISTORY In 1978, an actinomycete was isolated at 

The Kitasato Institute from a soil sample collected at Kawana, Ito City, japan

 the product was introduced commercially (in 1981) for the control of endoparasitic nematodes and ectoparasitic arthropods in livestock. 

CHEMICAL COMPOUND AVERMECTIN

Other anthelmintics derived from the avermectins include : 

Ivermectin Selamectin Doramectin Abamectin

MECHANISM OF ACTIONThese drugs bind to glutamate-

gated chloride channels in nerve and muscle cells

Increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell.

AVERMECTIN THERAPY

A commonly used therapy in recent times has been based on

oral parenteral topical spot topical flea repellant "drops administration of avermectins.

They show activity against a broad range of nematodes and arthropod parasites of domestic animals

Oral adminsteration

Subcutaneous asdminstration

TOXICITY AND SIDE-EFFECTS

Avermectin therapy is not without its drawbacks.

Resistance to avermectins has been reported, which suggests use in moderation. 

Research on ivermectin, piperazine, anddichlorvos in combinations also shows potential for toxicity.

TOXICITY AND SIDE-EFFECTS Avermectin has been reported to block LPS-

induced secretion of tumor necrosis factor, prostaglandinE2.

Increase of intracellular concentration of Ca2+.

TOXICITY AND SIDE-EFFECTS Side effects are usually transient; severe

effects are rare and probably occur only with substantial overdose, but include coma, hypotension, and respiratory failure, which can lead to death. No specific therapy exists, but symptomatic management usually leads to a favorable prognosis.

Ivermectin

IVERMECTIN

Is a broad-spectrum antiparasitic drug in theavermectin 

family. It is sold under brand names HeartgardIvomec worldwide by Merial Animal Health, Mectizan

Ivermectin is used against many intestinal worms (but not tapeworms),

Like mites, and some lice. Despite this, it is not effective for eliminating ticks, flies, flukes, or fleas. It is effective against larval heartworms.

intestinal worms

mites

Strongyles in horse

Heart worm

MICHANISM OF ACTION Bind to glutamate – chloride channels Increase permeability cell membrane to chloride

Ion Result paralysis and death

Selective toxicity :• Avermectin have low affinity for mammalian

ligand-gate chloride channel.

o Pharmacokinetcs :• Well absorbed orally and metabolizes in liver • Excreted in feces and urine

Drugs and/or metabolites are excreted almost exclusively in the feces over an estimated 12 days

Less than 1% of the administered dose excreted in the urine.