You need to decide what is worse - the illness you are treating verses the possible stress of the med - if used as directed, I have never really had a major problem with meds - if the ailment is low key, always go for the big water change first - improve the water quality. Use the med with the least side affects for the fish you have that will treat the specific ailment. Dose per actual gallons - take into account rocks, gravel, etc. Good luck!