Can you develop resistance to ppi drugs after long years usage? omeprazole then lansoprazole and others no longer working?

PPI resistance has been described and is always possible, at this point revisiting with treating gastroenterologist is strongly recommended as an upper endoscopy may be needed.

It may not be a case of developing resistance to the medication, but that your acid reflux or whatever is causing your underlying symptoms is worsening. Regardless, it sounds as though a follow up visit to your gastroenterologist is in order to sort it out and get you on therapy that works for you. Good luck.