Why a fifth rate with 42-pounders would be inefficient

Could a fifth rate be designed to carry 42-pounder cannon on its gun deck?

Yes, but it would be expensive and heavily built, with too little volume of fire for its likely opponents.

A fifth rate could be built to carry 42-pounders, but supporting them would require an unusually heavy and expensive structure. The resulting battery would also fire too slowly for the likely opponents of that type of ship. The objection concerns the combination of cost, structure, and useful volume of fire, rather than an absolute inability to fit the guns.