Opioids can act as agonists (bind and stimulate receptors), antagonists (bind and block or inhibit activity), partial agonists (bind and stimulate, but with less than full activity at certain receptor subtypes), and mixed agonist/antagonists (stimulating some receptors while blocking others).

Opioids are useful in a variety of chronically painful conditions (though they may have limited effectiveness in some forms of neuropathic pain). For the purposes of chronic pain management, only the oral and transdermal versions of various opioids will be considered in the following discussion.

Pure mu agonists provide the best analgesia, but also have the potential to produce the most side effects (bradycardia, hypotension, sedation, respiratory depression, urinary retention, vomiting, defecation, constipation). Their use is best limited to short-term “rescue” analgesia, though certain disorders (especially cancer pain) may require continual usage in the later stages of the disease. With chronic use, tolerance often develops, necessitating progressively higher doses to achieve an analgesic effect.

Morphine sulfate (CII) is available in oral tablet, capsule and liquid preparations. A suggested dose range in dogs is 0.5-2.0 mg/kg QID (some dogs experience unacceptable constipation at doses exceeding 1 mg/kg). Cats have been dosed with the liquid form at 0.2-0.5 mg/kg TID-QID, but most cats strongly dislike the taste.

Codeine has also been used as an oral mu agonist, though it is usually less efficacious than morphine. It is most commonly available in combination with acetaminophen as a CIII preparation, and is generally dosed in dogs at 1-2 mg/kg of the codeine portion TID-QID (it should NOT be used in cats in combination with acetaminophen due to the risk of fatal methemoglobinemia).

Fentanyl is available as a transdermal patch (Duragesic -- CII) in 25, 50, 75 and 100 ug/hour strengths. Some studies suggest the 75 and 100 ug patches may not provide consistent plasma levels; combinations of 25 and 50 ug patches can be used to achieve the appropriate dose (2-4 ug/kg) in dogs. In cats > 2.5 kg, a whole 25 ug patch is used; if < 2.5 kg, half of the plastic backing covering the gel is removed (DO NOT CUT patches).

Duragesic patches provide very good background analgesia, though they occasionally need to be supplemented with oral mu agonists. In dogs, the onset time is 12-36 hours, with a 72 hour duration of effect. Cats tend to have a faster onset time (5-8 hours) and a longer (up to 120 hours) duration. Side effects may include inappetance, agitation/dysphoria, sedation and hyperthermia (cats).

Partial mu agonists bind at the mu receptors but only partially activate them. Buprenorphine (CIII) is the prototypical drug in this class; it’s moderately expensive but VERY safe, producing few side effects and minimal sedation. Buprenorphine has tremendous affinity for the mu receptors, and will competitively inhibit pure mu agonists from binding. This property makes it useful for “reversing” the effects of morphine or fentanyl if adverse consequences arise, while still maintaining a level of analgesia.

A ceiling effect on analgesia exists with partial agonists, making them less useful for severe pain. Buprenorphine is interesting in that increasing the dose prolongs the duration of analgesia, while the degree of pain relief remains essentially unchanged. Doses of 30 ug/kg (0.030 mg/kg) will provide ~ 8-10 hours of analgesia, and 40 ug/kg (0.040 mg/kg) may produce as much as 12 hours of pain control. The onset of action is fairly slow (~ 30 minutes when given IV, 60 minutes IM, transmucosal or transdermal).

Buprenorphine is not available as an oral preparation (significant first-pass effect renders it inactive), but its lipophilic nature lends itself to absorption across skin or mucous membranes. Compounding pharmacies can produce a PLO (pleuronic lecithin organogel, or transdermal gel) for application on the inner surface of the pinna or shaved skin on the neck in dogs and cats. Alternatively, the alkaline salivary pH of cats allows for excellent transmucosal absorption when the injectable drug is given in the mouth (it should not be mixed with flavored syrups, as swallowing will inactivate it; the injectable form is tasteless and well-tolerated by cats). No studies have been performed on transmucosal usage in dogs, though the pH of their saliva is closer to that of humans, where bioavailability after mucosal administration is only ~ 30%.

Mixed agonist/antagonists like butorphanol (CIV) are not considered useful in the management of chronic pain. First-pass effect destroys some of the drug, and the analgesia is considered to be relatively short-lived (1-2 hours). Because these drugs are kappa agonists and mu antagonists, the pain relief is often less than optimal for chronic discomfort. However, visceral nociception is considered to be more responsive to kappa agonism, leading some urologists to advocate butorphanol’s use in chronic bladder pain (FLUTD).

Dr. Dave Thompson

1)   BUPRENORPHINE

a)      Classification

i)        Opioid

(1)   Partial mu agonist of extremely high affinity

(2)   Some kappa antagonism

(3)   Class III

b)      General Information

i)        Good all around analgesic for mild to moderate pain free of any expected undesirable effect

(1)   Anecdotal reports of dogs receiving 0.2 mg/lb IV on a QID basis for several doses without negative consequences (M. Richey, DACVA)

ii)       Minimal, if any, sedative effect

iii)     Buprenorphine has a delayed onset

(1)   30 minutes to peak effect when given IV

(2)   45 to 60 minutes to peak effect when given IM

iv)     Duration of effect is influenced by dose

(1)   3 to 4 hours at 0.010 mg/kg (0.005 mg/lb) dose

(2)   6 to 8 hours at 0.020 mg/kg (0.010 mg/lb) dose

(3)   8 to 10 hours at 0.030 mg/kg (0.015 mg/lb) dose

(4)   10 to 12 hours at 0.040 mg/kg (0.020 mg/lb) dose

c)      Advantages/Recommended use

i)        General soft tissue surgery

ii)       Light orthopedic surgery

iii)     In cats, studies have shown that bioavailability is the same whether given IV, IM, or via buccal oral mucosa (bioavailability is poor from GI tract – give sublingually or in lateral cheek pouch)

(1)   This transmucosal absorption is influenced by the alkaline pH of feline saliva

(a)    There is, as yet, no support for effective oral absorption by the dog

(2)   Excellent option for home analgesic management in cats

d)      Cautionary Information

(1)   Difficult to reverse if undesirable effects arise

(2)   Would be expected to antagonize other pure mu agonists like morphine, hydromorphone, fentanyl, and oxymorphone

e)      Dosage Information

(1)   Dogs – 0.010 to 0.040 mg/kg (0.005 – 0.02 mg/lb) IM or IV

(2)   Cats - 0.010 to 0.040 mg/kg (0.005 – 0.02 mg/lb) IM, IV, or Tramsmucosally

f)       Cost

i)        Moderate at low end of dose range - high at upper dose range

2)   BUTORPHANOL

a)      Classification

i)        Opioid

(1)   A mixed agonist/antagonist with primary agonistic activity at the kappa receptor

(a)    Generally antagonistic at the mu receptor

b)      General Information

i)        Good all around analgesic for mild pain free of any expected undesirable effect

ii)       Little, or no respiratory depression at clinical doses

iii)     Duration of effect is 30 minutes to 1 hour in dogs and 1 to 3 hours in cats

c)      Advantages/Recommended use

i)        General soft tissue surgery

ii)       More effective for visceral (soft tissue) than somatic (orthopedic) analgesic

d)      Cautionary Information

i)        Short duration of effect

(1)   Dogs - 30 minutes to 1 hour

(2)   Cats - 1 to 3 hours

ii)       Higher doses can produce excitement and dysphoria

e)      Dosage Information

i)        Dog & Cats

(1)   0.2 to 0.4 mg/kg (0.1 to 0.2 mg/lb) IV, IM, SC

(a)    0.2 mg/kg (0.1 mg/lb) is the most commonly selected dose

f)       Cost

i)        Moderate (to high if given every few hours)

3)   DURAMORPH®

a)      Classification

i)        Preservative free morphine

ii)       Pure mu opioid agonist

b)      General Information

i)        A specific preparation for epidural use

c)      Advantages/Recommended use

i)        Epidural analgesia

d)      Cautionary Information

i)        Single use 10 mg (10 ml) vials and 2 mg (2ml) vials - do not save residual meds

e)      Dosage Information

i)        Epidural use

(1)   Dog & Cat - 0.1 mg/kg (0.045 mg/lb.)

(a)    1 cc per 10 kg

f)       Cost

i)        Moderately high – significant wastage

4)   FENTANYL

a)      Classification

i)        A pure mu agonist

b)      General Information

i)        Duration of effect is 30 to 45 minutes

c)      Advantages/Recommended use

i)        Short-term analgesia

(1)   Excellent as an intra-operative “top up” analgesic

ii)       Induction agent when combined with a benzodiazepine

iii)     CRI analgesic use

d)      Cautionary Information

i)        May see panting and muscle rigidity

e)      Dosage Information

i)        Induction

(1)   See Diazepam & an Opioid section under Induction protocols for details

ii)       Analgesia

(1)   Bolus – 0.002 mg/kg (0.001 mg/lb)

(2)   CRI – 0.001 to 0.004 mg/kg/hr (0.005 to 0.002 mg/lb/hr)

(3)   Duragesic patch – based upon weight

(a)    Small dogs and cats, use the 25 mcg/hr patch but only expose ½ of the patch

(b)    For even smaller cats consider exposing ¼ of the patch

(c)    Never cut the patch

(d)    Clip hair as closely as possible at planned patch site without irritating the skin. Gently wipe area once or twice with slightly dampened gauze to remove loose hair. Let area dry. Warm patch to body temperature. Remove backing and apply patch to skin. Hold firmly against skin with hand for 2 full minutes. White tape and Kling gauze are used to cover and support the patch when possible.

f)       Cost

i)        Low per IV use

ii)       High per patch

a)      Classification

i)        Pure mu agonist

(1)   Class II

b)      General Information

i)        Duration of effect is 4 to 6 hours

ii)       Considered to have similar overall properties when compared to oxymorphone although less potent

c)      Advantages/Recommended use

i)        General premed for anesthetic candidates in all categories

ii)       Generally less panting than oxymorphone

iii)     Unlike Morphine, should not cause transient hypotension

(1)   IV use is not associated with histamine release

d)      Cautionary Information

i)        Bradycardia is common

ii)       Vomiting is common after IM administration

iii)     There is moderate sedative synergism between hydromorphone and acepromazine in the dog

(1)   Acepromazine doses should be kept at the lower end of the dose range

iv)     There is a tendency for cats to be agitated unless higher Acepromazine doses are used

e)      Dosage Information

i)        Dog – 0.01 to 0.4 mg/kg (0.05 - 0.20 mg/lb) IV, IM

(1)   Generally 0.1 to 0.2 mg/kg (0.05 to 0.10 mg/lb)

ii)       Cats – 0.05 to 0.2 mg/kg (0.025 - 0.10 mg/lb) IV, IM

(1)   Generally 0.05 to 0.1 mg/kg (0.025 to 0.05 mg/lb)

iii)     Induction

(1)   IV induction #2 - combined with fentanyl, hydromorphone, or oxymorphone – most useful for dogs

(a)    See Diazepam & an Opioid section under Induction Protocols for details

iv)     Maintenance

(2)   IV maintenance – most useful for dogs

(a)    See Diazepam & an Opioid section under Maintenance Protocols for details

v)      Epidural dose

(1)   0.03 to 0.10 mg/kg (0.015 to 0.05 mg/lb)

f)       Cost

i)        Low

6)   MORPHINE SULFATE

a)      Classification

i)        A pure mu opioid agonist

b)      General Information

i)        Duration of effect is 4 to 6 hours

c)      Advantages/Recommended use

i)        General premed suitable for healthy animals

ii)       Most commonly used in combination with acepromazine, an alpha-2 agonist, or a benzodiazepine sedative/tranquilizer

iii)     May provide greater sedation than can be achieved with hydromorphone or oxymorphone

d)      Cautionary Information

i)        Higher dosages can cause bradycardia and respiratory depression

ii)       More likely to cause transient hypotensive than hydromorphone, fentanyl, or oxymorphone

iii)     Often causes vomiting and defecation when given IM or SC

iv)     IV use is associated with histamine release

(1)   This is generally considered to be a transient low level concern and is unlikely if administered slowly

v)      There is significant sedative synergism between morphine and acepromazine in the dog

(1)   Acepromazine doses must be reduced appropriately

vi)     Should be used with caution in the cat if no sedative/tranquilizer is used

e)      Dosage Information

i)        Dog – 0.5 to 1.0 mg/kg (0.25 to 0.50 mg/lb) SC, IM, or slowly IV

(1)   Acepromazine dose would be low end – 0.005 to 0.040 mg/kg (0.0025 to 0.020 mg/lb)

ii)       Cats – 0.25 to 0.5 mg/kg (0.125 to 0.25 mg/lb) SC, IM, or slowly IV

(1)   Acepromazine dose must be higher end – 0.06 to 0.1 mg/kg (0.03 to 0.05 mg/lb)

iii)     Other uses

(1)   Constant rate infusion – see section on CRIs

(2)   Epidural – see section on epidurals

f)       Cost

i)        Low

7)   NALOXONE

a)      Classification

i)        An opioid antagonist

b)      General Information

i)        A short acting, pure antagonist

c)      Advantages/Recommended use

i)        To reverse unwanted effects of opioid medications

(1)   Can use small doses to partially reverse opioid effects

ii)       Duration of effect is 1 to 3 hours

d)      Cautionary Information

i)        Generally of shorter duration than most opioid agonists

(1)   Reversal effect may wear off before agonist has been cleared from body

(2)   Redosing may be necessary after 1 to 3 hours if undesirable agonist influence returns

ii)       Buprenorphine effects may not be reversible due to the high binding affinity

iii)     Butorphanol may not reverse as completely as pure Mu opioid agonists

e)      Dosage Information

i)        Dog & Cats - ).02 to 0.1 mg/kg (0.01 to 0.05 mg/lb) IM or IV

(1)   Give 1/4 of calculated dose every 3 - 4 minutes until desired effect is achieved

f)       Cost

i)        Moderately low

8)   OXYMORPHONE

a)      Classification

i)        A pure Mu opioid agonist

b)      General Information

i)        Duration of effect is 4 to 6 hours

c)      Advantages/Recommended use

i)        General premed for anesthetic candidates in all categories

ii)       Hypotensive patients

(1)   Unlike morphine, should not cause transient hypotension

iii)     Higher risk patient when the risk of vomiting needs to be minimized

d)      Cautionary Information

i)        Bradycardia is common

ii)       Noise hypersensitivity may be a problem

iii)     There is moderate sedative synergism between oxymorphone and acepromazine in the dog

(1)   Acepromazine doses must kept at the lower end of the dose range

iv)     Should be used with caution in the cat if no sedative/tranquilizer is used

e)      Dosage Information

i)        Dog – 0.05 to 0.2 mg/kg (0.025 - 0.050 mg/lb) IM, IV

ii)       Cats – 0.025 to 0.05 mg/kg (0.01 - 0.025 mg/lb) IM, IV

(1)   Combine with acepromazine 0.06 to 0.10 mg/kg (0.03 to 0.05 mg/lb)

f)       Cost

i)        High

Dave Thompson & Bob Stein