a revolutionary “wonder-drug” being the 1st endectoside which was developed in the late 1970's derived from avermectin which was discovered in soil with a Japanese organism that produced it.1)
it has played a major role in under-developed countries fighting onchocerciasis / river blindness since 1988, and lymphatic filariasis as well as for treating livestock and pets
it is effective against a wide range of parasites, including gastrointestinal roundworms, lungworms, mites, ticks, lice and hornflies
acts on glutamate-gated Cl− channels (GUCl−) (to paralyze body-wall and pharyngeal muscle) that only occur in insects and nematodes but not in vertebrates
it also seems to disrupt the fundamental host-parasite equilibrium and it may interfere with the ability of microfilariae to evade the human immune system, resulting in the host’s own immune response being able to overcome the immature worms and so kill them
it has proved to be astonishingly safe for human use
Pharmacology
available as a topical cream or lotion and as oral tablets
half-life of ivermectin in humans is 12–36 hours, while metabolites may persist for up to three days
Ivermectin overdose / poisoning
at usual doses, ivermectin is not thought to readily cross the blood-brain barrier (BBB) in humans and other vertebrate animals as it is excluded by a ABCB1 P-glycoprotein drug pump (mdr-1) HOWEVER, it may cause CNS toxicity2):
in overdose
in those with genetic variants of mdr-1 (some humans, certain breeds of dogs such as collies)
those with impaired BBB (eg. sepsis, malignancy)
those taking other medications which compete for mdr-1 (eg. CYP3A4 substrates such as statins, HIV protease inhibitors , calcium channel blockers, benzodiazepines)
in humans without the above risk factors, it appears CNS toxic effects generally do not occur under 10x the maximum FDA dose of 200 µg/kg.3)
CNS toxicity causes a GABA-induced cholinergic syndrome
clinical features
gastrointestinal effects (nausea, vomiting, abdominal pain, and diarrhea)
headache, blurred vision, dizziness
tachycardia, hypotension
visual hallucinations, altered mental status, confusion, loss of coordination and balance, CNS depression, and seizures
may increase sedative effects of other medications such as benzodiazepines and barbiturates