Morphine

Morphine is one of the oldest and most widely used opiates.  It originates from the opium alkaloids which are derived from a species of poppy known as Papaverum somniferum.  Morphine and other opium-derived opioids are a cornerstone for pain management in human and veterinary medicine.  Because of their propensity to create addiction and their widespread abuse, opioids are tightly regulated and becoming difficult to obtain. 

Morphine is a full agonist opioid meaning it has activity at all identified opioid receptors δ (delta) μ (mu), and κ (kappa) including the fourth opioids receptor, nociception receptor. However, its main effect is to bind with the mu receptor in the central nervous system. Even though it was first isolated as early as 1804, morphine is, today, what all other opioids are compared to with regards to potency. 

Its versatility stems, in large part from its wide range of routes of administration including oral, rectal, subcutaneous, intramuscular, intravenous, epidural, intra-articular, even topical (i.e. the cornea). However, it is understood that intramuscular administration will likely cause vomiting. Caution should be used when delivering morphine intravenously, as rapid administration is associated with histamine release.

The average duration of action from a single dose is 3-4 hours.1, 2 When placed within the epidural space, duration of effects are reported to last 12-24 hours.3 

Because they work synergistically or additively with the effects of other drugs used during anesthesia, morphine and other opioids can produce dose dependent respiratory and cardiovascular depression.  When using opioids during an anesthetic event, these synergistic or additive effects must be properly considered and doses adjusted accordingly. 

However, when used at appropriate doses, with or without other medications in well-monitored patients, morphine is considered relatively safe, especially as it is reversible with an opioid antagonist, such as naloxone or naltrexone. Morphine is metabolized via conjugation with glucuronic acid into the active metabolite morphine-6-glucuronide (M6G) and inactive metabolite morphine-3-glucuronide both which are eliminated by the kidneys.

Although morphine is the oldest and perhaps best known opioid, others such as hydromorphone, oxymorphone, methadone, fentanyl, remifentanil, sufentanil, alfentanil, meperidine, codeine, oxycodone, hydrocodone, etorphine, carfentanil, butorphanol, nalbuphine, and buprenorphine have been developed demonstrating different potencies, durations of action, receptor activity and side effect profiles.

Below is a table showing products within the USA registered for veterinary and or human use:

Chemical Name

Potency (mg kg-1) versus morphine

Receptor binding
agonist/antagonist

CVM drug approval

FDA drug approval

CVM drug approval example

morphine

1

µ agonist

No

Yes

none

methadone

1

µ agonist

No

Yes

none

buprenorphine

3-5

partial  agonist, high affinity, low activity

Yes

Yes

Simbadol® 
(cats, SC)

butorphanol

4-7

µ antagonist/ agonist

Yes

Yes

Torbugesic® 
(dogs, cats, horses; IV, SC, PO)

oxymorphone

5-10

µ agonist

Yes

Yes

Numorphan® 
(dogs and cats; IV, SC, IM)

hydromorphone

5-10

µ agonist

No

Yes

none

fentanyl

100

µ agonist

Yes

Yes

Recuvyra® 
(dogs, topical)

remifentanil

100

µ agonist

No

Yes

none

sufentanil

500-1000

µ agonist

No

Yes

none

carfentanil

10,000

µ agonist

Yes

No

Wildnil® 
(deer, elk, moose)