Drug is used mainly at first after surgery (5)
I believe the answer is:
opium
'drug' is the definition.
(opium is a kind of drug)
'is used mainly at first after surgery' is the wordplay.
'at first' suggests taking the first letters.
'after' is a charade indicator (letters next to each other).
'surgery' becomes 'op' (short for operation).
The first letters of 'is used mainly' is 'ium'.
'ium' after 'op' is 'OPIUM'.
(Other definitions for opium that I've seen before include "Derivative of Poppy" , "Poppy drug" , "Narcotic derived from poppies" , "The stuff of wars" , "analgesic" .)