Use in turtles is particularly contraindicated.A characteristic of the antinematodal action of ivermectin is its potency: for instance, to combat Dirofilaria immitis in dogs, ivermectin is effective at 0.001 milligram per kilogram of body weight when administered orally.For dogs, the insecticide spinosad may have the effect of increasing the toxicity of ivermectin. Pharmacology
Mechanism of action
Ivermectin and its related drugs act by interfering with the nerve and muscle functions of helminths and insects. The drug binds to glutamate-gated chloride channels common to invertebrate nerve and muscle cells. The binding pushes the channels open, which increases the flow of chloride ions and hyper-polarizes the cell membranes, paralyzing and killing the invertebrate. Ivermectin is safe for mammals (at the normal therapeutic doses used to cure parasite infections) because mammalian glutamate-gated chloride channels only occur in the brain and spinal cord: the causative avermectins usually do not cross the blood–brain barrier, and are unlikely to bind to other mammalian ligand-gated channels. Pharmacokinetics
Ivermectin can be given by mouth, topically, or via injection. It does not readily cross the blood–brain barrier of mammals due to the presence of P-glycoprotein (the MDR1 gene mutation affects the function of this protein). Crossing may still become significant if ivermectin is given at high doses, in which case brain levels peak 2–5 hours after administration. In contrast to mammals, ivermectin can cross the blood–brain barrier in tortoises, often with fatal consequences. Chemistry
Fermentation of Streptomyces avermitilis yields eight closely related avermectin homologues, of which B1a and B1b form the bulk of the products isolated.
Signs and symptoms
Fear, discomfort or anxiety may be triggered both by the presence and the anticipation of the specific object or situation. The main behavioral sign of a specific phobia is avoidance. The fear or anxiety associated with specific phobia can also manifest in physical symptoms such as an increased heart rate, shortness of breath, muscle tension, sweating, or a desire to escape the situation. Causes
The exact cause of specific phobias is not known. The mechanisms for development of specific phobias can be distinguished between innate (genetic and neurobiological) factors, and learned factors. In neurobiology, one explanation proposed for specific phobia is that the typical activation of the amygdala in response to stimuli may be exaggerated due to pathological changes. According to this theory, a deficiency in amygdala habituation may also contribute to the persistence of non-experiential phobia. Certain phobias that are less lethal (e.g. dogs) seem to be more frequently observed and easily acquired in comparison to potentially lethal fears which are more relevant to developed human society (e.g. cars and guns). This was theorised to be due to biological adaptation being passed through evolution which makes recent threats less prone to easy acquisition. However, a 2014 study found evidence against this evolutionary theory, which stated: "Our findings are inconsistent with the hypothesis that fears/phobias of individual stimuli result from genetic and environmental factors unique to that stimulus. Instead, we observed substantial sharing of risk factors across individual fears."