MACROCYCLIC LACTONES (MACROLIDES (AVERMECTINS AND MILBEMYCINS)

Question 1

SUBSTANCES

Answer 1

Avermectins:
Abamectin, Doramectin, Eprinomectin, Ivermectin, and Selamectin

Milbemycins:
Moxidectin and Milbemycin oxime

Potent ectoparasiticides as well – called as endectocides

Semi-natural fermentation products (i.e antibiotics) of Str. avermitilis and cyanogriseus.

Question 2

MECHANISM OF ACTION

Answer 2

Potentiation of inhibitory transmitters by binding to glutamate- & GABA-gated (weaker) Cl- channel receptors in nematode & arthropod nerve cells.
This causes the channel to open, allowing an influx of chloride ions.
Macrocyclic lactones paralyze the pharynx, the body wall, and the uterine muscles of nematodes.

Question 3

ANTHELMINTIC SPECTRUM

Answer 3

Adult, immature nematodes, including hypobiotic larvae, microfilariae /+ arthropods/. Resistance may occur (parallel with BZs and Levamisole).

Question 4

PHARMACOKINETIC FEATURES

Answer 4

Lipophilic compounds, good absorption, wide distribution. Accumulation in fatty tissue, long lasting effect, residues.
SIDE-EFFECTS The therapeutic index (TI) for the macrocyclic lactones is typically moderate-wide (10) (but Abamectin and Moxidectin are contraindicated in calves and foals < 4 months old). Mammalian safety appears to depend on P-glycoprotein activity in the blood-brain barrier. There have been cases of CNS depression in cattle breeds (Murray Grey) and purebred and crossbred Collies. Nervous system signs (idiosyncratic reactions) including depression, muscle weakness, blindness, coma, and death were observed, especially in Collies.

Question 5

APPLICATION

Answer 5

• regular doses of ivermectin
• SC- injection- Ruminants 0.2, Swine 0.3 mg/kg B.W.
• PO- Swine premix (0.1), Horses paste (0.2), /Dogs in tablets 0.06/
• DERMAL (Pour on)- 0.6-0.8