If there is just no way you can get a flight from any airline that is a direct, single-plane flight, then you should request a layover of at least two hours at any stop where a change of planes will occur. This way you have the opportunity to make sure all is going right before you and your dog take off again. You also have the opportunity to exercise and water your dog at the layover point. Call the airline and confirm both your and your dogs flight and ask where to check your dog in. Unless there is a medical reason, do not tranquilize or sedate your dog.
Dogs are more apt to have side effects from the drug than to the flight itself.
You may be a nervous flier, but don't assume your dog is too. To him it's just another ride to the show. Feed lightly the day before. Toys or rugs in the crate should be large enough not to be eaten or choked on. Your dog will be out of sight for 1 - 5 hours so don't take chances on smaller toys.