I crossed over this question, and couldn't find the right answer.

The old pt. after hip replacement surgery is getting morphine for a longer period of time. Her respiration came to 6/min.
What is the reason of this patient deterioration after the initiation of morphine.
1.Chronic dosing of morphine decreases its bioavailability.
2.Morphine bioavailability increases with chronic dosing.
3.Morphine downregulates mu receptors with chronic dosing.
4.Morphine inhibits its own metabolism.
5.Morphine is metabolized to active metabolites that accumulate.

Could you please help with this.
Thanks, Dusha