Do you have your feet attached to the pedals? Straps, cages, clipless, etc? That will help alot once you're up to speed as the more you get used to it the more you pull up slightly while you're pushing down, and because the cranks carry themselves as the bike moves forward once you're up to cadence there won't be much resistance to keep going at speed, the added pulling up makes it even more minimal... In my experience higher gearings aren't necessarily much harder to keep going once they're up to speed, it's just the stopping and getting up to speed that become harder.

Although I might be the outlier with a 52/14 and a 48/16, my knees do sometimes feel like they're going to asplode but I fly past roadies (they usually catch up a couple minutes down the road when I'm hyperventilating though)