They do. The problem lies that ones individual physiological reaction to hypoxia is unique. One of the problems is a sense of euphoria and well being the more it progresses so if your symptoms take hold before you have a chance to let your training kick in you'll possibly find yourself in a very poor situation.
Having never flown a 421 I'm not sure how their system works short of some very rudimentary basics so I can't comment. With a recent maintenance issue with the pressurization system it's not unheard of to have an undiscovered problem upon return to service.
Case in point, my last 2 trips to the service center for my airplane included the airplanes air/ground logic being confused. The stall warning and stick shakers were going off on the ground and even the satellite phone was acting weird. The problem was an unplugged squat switch that would/should be discovered on even the most basic return to service check. It wasn't.
The most recent I had the left engine pulled to replace all the seals and some ducts to rectify some high pressure bleed leaks that were an ongoing problem and band-aid fixes weren't cutting it. During the return to service checks it never came up to check the thrust reverser (a pretty simple pair of hydraulic actuators) were operating. On taxi out, the right was fine and the left was spazzing out for lack of a better phrase. After moving at a snails pace and my coworker and I rolling up our own sleeves to motivate the second shift weekend crew (not the varsity team) we got it bled and it worked fine.
What's the best way to screw up a perfect working airplane? Take it in for scheduled service.
There's no way to know at this point the nature of the exact failure experienced in this case. It may never be known but my attention would be put on a pressurization issue not only because it was recently worked on but the nature of the behavior of the airplane during the course of the flight.
