It really depends on the opponent hand. if they have a damage reducer, there is a higher chance that they will Tank your damage.
if they have a defeat card, there is a higher chance they will Tank your attack.
if they have a revenge card, and one of the other types mentioned previously...
chances are even higher that they will Tank your attack.
of course it all depends on the player.
some players will use the fact that they have defeat, revenge, and damage reducers against you.
it all comes down to... how much risk you're willing to manage.
if they have a reducer, if you go 0 pillz, and they win, will it force you to be on the defensive?
because if they're good, Lucky, or otherwise able to thwart your moves, you'll have to play more spontaneous.
if they have all defeat/reducer cards... then it's a gamble... it's always a gamble.
it's a dog eat dog world out there.
Look at the damage they can make and you can make provided your damagers does not have very low round winning abilities, from that point you can decide which card to play first and whether to pill or not pill (or a little).
and yeah, try not to lose the match instantly if you get perfect pilled or good pilled in the first round.
the safe thing to do with Uppers would be olding (0pill)
Depends entirely on the clan I'm playing and the cards my opponent draws. There are so many variables I don't think you can have it down to an exact science, you can't be too rigid because that's how you end up making mistakes. I generally don't mind bluffing the first round and then losing, because unless my opponent has a OHKO I'm not that worried. And a lot of times that bluff turns out to be an advantage because if you end up winning that round its a huge plus. Using Uppers always helps haha. I love Uppers for that reason, its either pill or lose.