A different variation of a widely used term,"What's up?"

1. To make a mistake; bungle something.
2. To act carelessly, foolishly, or incorrectly.
3. To cause to be intoxicated.

Pretty much an accurate description of the Presidency of George W. Bush.

The point at which one has become extremely intoxicated from either alcohol, or drugs.

To mess things up; to make the same mistake repeatedly

A failure at everything, total loser, unable to do anything right

means to be really messed up usually referring to the head.