Careless mistakes lead to horrific overdose (8)
I believe the answer is:
slipshod
'careless' is the definition.
('slipshod' can be similar in meaning to 'careless')
'mistakes lead to horrific overdose' is the wordplay.
'mistakes' becomes 'slips' (slip is a kind of mistake).
'lead to' says to take the initial letters.
'overdose' becomes 'od' ('o.d.' can be a synonym of 'overdose').
The first letter of 'horrific' is 'h'.
'slips'+'h'+'od'='SLIPSHOD'
(Other definitions for slipshod that I've seen before include "Haphazard, slapdash" , "Careless in thought or organisation" , "Sloppy and haphazard" , "Disorganised" , "Loose" .)