Ivermectin- Mechanism of action; Indications; Toxicity (Antihelminthics/ Anthelmintics)

The content of the video:
Goals: (0:00)
Cross-section of Ascaris lumbricoides: (0:10)
Ivermectin- Mechanism of action : (0:35)
Ivermectin Analogs (Avermectins) : (1:15)
Ivermectin- Is it Toxic?: (1:36)
Ivermectin- Indications: (5:30)

In this video, we'll discuss the mechanism of action of ivermectin and its analogs.
Ivermectin belongs to the group of avermectins. Avermectins are a group of drugs that includes ivermectin, selamectin, doramectin, eprinomectin, and abamectin. They have the same mechanisms of action as ivermectin.
Ivermectin can be given by mouth, topically, or via injection.
To understand why ivermectin is relatively safe for mammals, meaning it doesn't paralyze and kill us too, we need to understand the concept and the structure of the blood-brain barrier.
The blood-brain barrier is the barrier between the cerebral capillary blood and the interstitial fluid of the brain. The blood-brain barrier is made up of capillary endothelial cells, with tight junctions between them, the basement membrane, pericytes embedded in the capillary basement membrane, and the foot processes of astrocytes. Now, I'll highlight the blood-brain barrier with this black rectangle.
It acts as a barrier between the bloodstream and the extracellular space of the brain, allowing only certain substances like water, oxygen, and small lipid-soluble substances to easily cross from the blood into the brain. This prevents toxins, pathogens, and other potentially dangerous substances like ivermectin for example, from crossing from the circulatory system into the brain.
Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur on the neurons located in the brain and spinal cord, in other words, on the neurons from the CNS. Ivermectin and avermectins, usually do not cross the blood-brain barrier due to the presence of the P-glycoprotein.
Now, let's zoom in on this portion. Here you can see the P-glycoprotein, located on the endothelial cells of the blood-brain barrier. The P-glycoprotein is one of the drug transporters that determine the uptake and efflux of a range of drugs. Ivermectin will get into the cell.
The P-glycoprotein pumps chemicals and possible toxins from the cell. In our case, the P-glycoprotein will pump the Ivermectin and Avermectins out of the cell, preventing their passage across the blood-brain barrier.
As a consequence, Ivermectin and Avermectins will not reach the receptors located on the neurons in the CNS. That's why Ivermectin is safe for mammals at therapeutic doses.
Now, let's zoom back in. I want to show you what happens at higher doses. If ivermectin and avermectins are given at high doses, the P-glycoprotein will not pump the Ivermectin and Avermectins out of the cell quickly enough. Crossing may become significant, in which case brain levels peak 2–5 hours after administration, and it can be very toxic. So, be careful with the dose.
Some examples of infections caused by insects, which can be treated with Ivermectin are: head lice infestation caused by the head louse, Pediculosis pubis caused by the pubic louse, and scabies caused by a mite called Sarcoptes scabiei, which is an arthropod, specifically an arachnid. Helminths are classified into roundworms, also known as nematodes, and flatworms. Flatworms are further classified into trematodes also known as flukes and tapeworms also known as cestodes. Some examples of infections caused by helminths, which can be treated with Ivermectin are: Ascariasis caused by Ascaris lumbricoides, Strongyloidiasis caused by Strongyloides stercoralis, Trichuriasis caused by Trichuris trichiura, River blindness caused by Onchocerca volvulus, and Lymphatic filariasis, which can cause elephantiasis. Lymphatic filariasis is caused by filarial worms, which are highly specialized parasitic nematodes, for example, Wuchereria bancrofti.