Sam's first instinct when he saw that gigantic purple frog was to go for his gun too. Because seriously-what was that? Frogs weren't supposed to be that big. His hand was halfway there when he locked eyes with the creature. Something in those eyes... he thought that he saw panic, and maybe something... familiar? Maybe?
His mind raced to analyze the situation and ran through a few hypotheses even as Dean pulled out his gun and pointed it. Sam didn't have much beyond instinct and a few theories, but that was enough that he stepped between the frog and his brother.
"Dean, wait. Don't."
He couldn't really explain why yet, partly because the leading theory in his mind involved something that he'd promised Jo he wouldn't talk about. But if he was right and Maxine somehow turned Fred into super-frog, well, Sam would never forgive himself if he let her get ganked right now. If he was wrong, then they would figure out what this thing was and get rid of it.