First off: For most individuals plain pediatric Benedryl (the versions without additives, please, since additives in some meds like Tylenol can be fatal for ferrets) is a very forgiving medication. You'd be shocked at the amounts they have to give me IV when I have general anesthesia and for a few days afterward. The rule of thumb though, is that when a very large dose is given then there needs to be supervision by medical personnel at that time. Pretreating is not done for sedation; it is done for the same reason that people who are prone to the severe form of allergic reaction called anaphylactic shock are pretreated before getting allergy shots (and, yes, it can be worth the risk when the person's lungs and life-style are compromised enough): to reduce the chances of a reaction and the severity of a reaction when one occurs. Fortunately, by now most people know to separate the shots (not give them in the same appointment) and to stay in the vet hospital for at least 45 minuted following a vaccination in case an anaphylactic reaction occurs. Because that results in rapid treatment deaths from such reactions are extremely rare. (This, BTW, is why your allergist says that adults and children who can express themselves should stay in the office for 20 minutes after shots -- longer for those who can not clearly express themselves, and that if any of a number of symptoms (flushing, throat closing or sore, difficulty swallowing, feeling of impending doom, hives, swelling, tiredness, sleepiness, etc.) appear that the nurses should be immediately notified so that the allergist can attend to it with medications which are similar to those used for the ferrets when they react.) BTW, I checked with multiple noted research professionals on allergies and on cardiac health and the last time I checked (sometime last year, I think) there were no indications in many mammals that past anaphylactic reactions increase the risk of later cardiomyopathy happening, so that old observation was hopefully a coincidence. (BTW, going form my personal experience, that of Steve and of 3 other members of our families who go into anaphylatactic reactions except when a feeling of impending doom occurs the symptoms look worse than they feel unless they advance the point where a respirator is needed or unless extreme dizziness, cramping, or over-response to the epi occur. When bloody runs occur during such a reaction it is not that the intestines are shredding or such; what is happening is that the fluid is being moved out so rapidly from the cappilaries that it is actually carrying red blood cells along and it just feels like having the worst runs of your life -- which is likely is unless you have had something like one of the old scurges that are mostly under control in industrial nations -- but no worse than that in pain so folks shouldn't imagine worse.) An allergic reaction occurs when the body became convinced after a previous exposure that a substance was an invader. The part of the immune system which tends to go off-kilter is one that normally handles parasites. Then the next time there is an exposure the reaction occurs. This is why true food allergies tend to be to preferred foods, why most allergy onsets happen in adulthood, etc. There are many hypotheses right now about why allergies happen: from homes that are too clean, to too much exposure to certain substances in susceptible individuals(such as favorite foods, high pollen counts, common matrices in vaccines, etc.), to genetics (tendency to allergies tends to run in families), to pollution levels increasing susceptibility, and so on. An anaphlactic reaction tends to kill by either smothering or by dipping the blood pressure too low to remain alive. (There are other serious types of allergic reactions which can be fatal -- from asthma, to one in which the tongue swells enough to shut off the airway, to a very rare form (luckily) of dermal necrosis which is a true horror.) [Posted in FML issue 3916]