I run into this problem frequently because I work from home. People don't seem to grasp that even though I work from my couch whilst wearing pajama pants, it's still work! And I need 6-8 hours of quiet, uninterrupted time to get it done every day. So no, I can't take your child while she's sick so you don't have to miss work. I can't take your child for weeks at a time during the summer. I can't take her for the day while you run errands - and yes, my deadlines do "really count."
The minute I see the conversation heading that direction, I mention something along the lines of, "Yes, it's difficult to find good childcare. I searched for months for the right preschool for my son because I knew I wouldn't be able to work with him in the house with all day."
and if they don't get the hint, I said, "I'm sorry, that won't be possible."
I really don't mind helping out after work hours for real friends who reciprocate. Our next door neighbors have asked me several times to get her kids off of the bus in the afternoons when they have to work past the drop off time. And I don't mind because 1) I've finished working at that point and 2) When I've had to dash out to pick my son up from preschool and the kids were playing, she's been willing to supervise my daughter and 3) Her kids are incredibly sweet and well-behaved.