Apendejan comes from the verb apendejar, which is a colloquial and somewhat vulgar term derived from "pendejo" (a common insult meaning 'idiot' or 'fool'). It means to make someone foolish or stupid.
In the song, Carín León sings, "Yo les canto, les encanto y me apendejan" (I sing to them, I charm them, and they make a fool of me). He uses this word to express how, despite his charm, the women he encounters still manage to outsmart him or make him act foolishly, adding a humorous and self-deprecating tone to the lyrics.
Carín León spends this one juggling a girlfriend, a wife and a woman from Medellín, and losing on all three counts. The opening line does the whole setup in one breath: "Hoy mi novia me dejó y mi esposa casi me deja" (Today my girlfriend left me and my wife almost left me), and the culprit is "una paisa medio fresa" (a slightly preppy girl from Medellín). He is not really apologising, either. His defence is that women simply fall for him: "¿Qué culpa tengo yo si del muñeco se enamoran?" (What's my fault if they fall in love with the pretty boy?).
The Juanes feature is the joke the whole song is built on. "Cambié mi camisa negra por la camisa de fuerza" (I changed my black shirt for the straitjacket) turns Juanes' own "La Camisa Negra" into the punchline of a man who has gone a bit mad over a Colombian girl, and the chorus keeps dragging him from north to south: "Me ando acordando de ti, mezclando guaro con Pielroja" (I'm remembering you, mixing guaro with Pielroja) puts Colombian aguardiente and Colombian cigarettes in the hands of a singer from Sonora. He packs anyway: "Yo me voy pa' Medellín aunque se agüite mi señora" (I'm going to Medellín even if my lady gets upset).