I wouldn't go worrying about the 6'3 300lbs guy on drugs. Because if you do you'd need to be carrying some serious firepower. Start with something small like a 8 inch barrel 500S&W! Handgun rounds are generally ineffective, especially against people like you describe. Plenty of people survived bigger and badder rounds. Sometimes multiple rounds.

380s lack penetration with HP and lacks wound cavity with FMJ. For me personally they also lack grip and sights. Even ignoring the sights there is not enough grip to shoot fast and accurate. Getting a bigger 380 like a Beretta 84 is pointless because at this point I'm carrying something the size of a compact duty gun so I may as well take advantage of that and use a 9mm.

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