Etorphine hydrochloride
Applications in Veterinary Medicine and Wildlife Management
Etorphine was the first potent opiate agonist employed primarily for use in non-domestic and wild species. Prior to its development and registration in the early 1960s, the only immobilization tools available were succinylcholine, nicotine sulphate, and ropes.
General Information and History
Etorphine revolutionized the ability of biologists and veterinarians to safely capture and restrain many species that previously could not be handled. Its reversibility with diprenorphine (M5050), a potent opiate antagonist, made it a significant advance in zoo and wildlife medicine. Etorphine hydrochloride was registered in the United States under the trade name of M99 by American Cyanamid. It was later registered in combination with acepromazine under the trade name of Immobilon in the United Kingdom. It is currently registered and available in South Africa under the trade name Captivon.
By virtue of its long history in veterinary medicine and wildlife biology, etorphine use
in numerous species is well documented in the literature. Although newer and more desirable opiates have been developed (carfentanil, A3080), etorphine is still the drug of choice for exotic equids, rhino, and other hoof stock.
Use in Wildlife Management
Etorphine’s potent opiate agonist activity produces rapid reversible immobilization at
low dose rates. It is routinely combined with azaperone, xylazine, or medetomidine. It
is rapidly reversed with naltrexone or diprenorphine.
Etorphine has been used in almost every wild and free-ranging group with the exception of members of the family Felidae which have severe and adverse reactions to all opiate agonists. In the United States, it has been extensively used in feral horses, deer, elk, bison and, to some extent, in bear in years past. Its availability in the late 1960s concurrent with the development of reliable dart delivery systems allowed wildlife managers and researchers to conduct projects and studies that previously were impossible In zoological collections it has been used in elephant, rhino and members of the family Equidae. Its use in other species in zoos has been replaced by carfentanil, medetomidine combinations, and Telazol in combination with alpha-two agonists (xylazine, medetomidine).
Use in Domestic Species
Etorphine has had limited use in domestic species in the United States due to its high opiate agonist potency and the level of DEA control on this substance.
Pharmacology and Chemistry
Etorphine is a full opiate agonist and binds to multiple opiate sites in the central nervous system. It is believed to produce its clinical effects through binding the µ-, δ-, and κ- opiate sites. It has a potent effect on depressing the respiratory centers of the CNS thus resulting in apnea being commonly seen in immobilized animals.
Etorphine is chemically related to morphine. In laboratory animals, etorphine resembles morphine by causing analgesia, catatonia, blockade of conditional reflexes, and anti-diuretic effect. It also resembles morphine by causing excitement in mice, cats and bradycardia and hypotension in rats, dogs, cats and monkeys. When given subcutane- ously, etorphine is 1000-4000 times more potent than morphine as an analgesic, depending on the test situation. Its use for immobilizing game animals results largely from its ability to cause catatonia at very low dose levels.
The chemical name for etorphine hydrochloride is 6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-3-hydroxy-6-methoxy-ά,17-dimethyl-ά-propyl-, (5ά,7á-(R))- hydrochloride.
Pharmacokinetics
The information available from pharmacokinetic studies with etorphine in target species is very scant. It is believed that the pharmacokinetic pathways and distribution of etorphine are not dissimilar to those of the other morphine base agonists.
CONTRAINDICATIONS AND PRECAUTIONS
Do not use Etorphine hydrochloride unless antidote or antagonist is on hand.
WARNING:
Adequate amount of a reversal agent, i.e. Naltrexone hydrochloride or Dipren- orphine (M5050) should be immediately available. Diprenorphine should never be used to antagonize etorphine in humans. Either naloxone (Narcan) or naltrexone should be used in the event of accidental human exposure.
RECOMMENDED DOSE RANGE
The literature regarding effective doses of etorphine in non-domestic species are extensive and beyond this monograph to list. General guidelines in the literature give the following dose rates applicable to North American species.
| Feral Equidae | 0.44 mg per 100 lbs | |
| Ursidae | 0.50 mg per 100 lbs | |
| Cervidae | 0.98 mg per 100 lbs | |
| Bovidae | 0.09 mg per 100 lbs |
Doses and protocols for individual species are readily available in the published literature.
DOSE RATE FOR AFRICAN SPECIES
SPECIES |
MASS KG |
ETORPHINE |
+ XYLAZINE |
+ AZAPARONE |
|||
µg/kg |
Total (mg) |
µg/kg |
Total (mg) |
µg/kg |
Total (mg) |
||
African elephant |
5000 |
1 – 1,25 |
5 – 15 |
- |
- |
- |
- |
Sq. Lipped Rhino |
2000 |
1 – 2 |
2 – 3 3 |
- |
- |
125 |
250 |
Black Rhino |
1000 |
2 – 4 |
2 – 4,5 |
- |
- |
250 |
250 |
Giraffe |
1000 |
2 – 10 2 |
2 – 10 |
30 – 50 |
30 – 50 |
50 – 150 |
50 – 150 |
African Buffalo |
700 |
7,5 – 15 |
5 – 12,5 |
50 – 100 |
35 – 70 |
50 – 150 |
35 – 105 |
Eland |
700 |
7,5 – 15 |
5 – 10,5 |
100 – 300 |
70 – 210 |
100 – 200 |
70 – 140 |
Blue Wildebeest |
200 |
10 – 20 |
2 – 4 |
50 – 100 |
10 – 20 |
150 – 300 |
30 – 60 |
Black Wildebeest |
150 |
10 – 20 |
1,5 – 3 |
50 – 100 |
7,5 – 15 |
150 – 300 |
22,5 – 45 |
Red Hartebeest |
140 |
15 – 25 |
2 – 3,5 |
50 – 100 |
7 – 14 |
150 – 300 |
21- 42 |
Lichtenstein Hartebeest |
200 |
15 – 25 |
3 – 4 |
50 – 100 |
10 – 20 |
150 – 300 |
30 – 60 |
Tsessebe |
140 |
15 – 25 |
2 – 3,5 |
75 – 150 |
10,5 – 21 |
150 – 300 |
21 – 42 |
Blesbok |
90 |
15 – 25 |
1,5 – 2,5 |
50 – 100 |
4,5 – 9 |
150 – 300 |
13,5 – 27 |
Greater Kudu |
250 |
15 – 25 |
4 – 8 |
50 – 100 |
12,5 – 25 |
150 – 300 |
37,5 – 75 |
Nyala |
100 |
15 – 25 |
1,5 – 2,5 |
50 – 100 |
5 – 10 |
150 – 300 |
15 – 30 |
Bushbuck |
50 |
15 – 25 |
1 – 1,5 |
50 – 100 |
2,5 – 5 |
150 – 300 |
7,5 – 15 |
Reedbuck |
70 |
15 – 25 |
1 – 2 |
50 – 100 |
3,5 – 7 |
150 – 300 |
10,5 – 21 |
Waterbuck |
250 |
15 – 25 |
4 – 8,5 |
75 – 150 |
18 – 36 |
150 – 300 |
37,5 – 75 |
Roan Antelope |
280 |
15 – 25 |
4,2 – 7 |
50 – 100 |
15 – 30 |
150 – 300 |
45 – 90 |
Sable Antelope |
240 |
15 – 25 |
3,6 – 6 |
50 – 100 |
12 – 24 |
150 – 300 |
35 – 72 |
Gemsbok |
200 |
15 – 25 |
3 – 6,5 |
50 – 100 |
10 – 20 |
150 – 300 |
30 – 60 |
Impala |
50 |
15 – 25 |
0,8 – 1,5 |
100 – 200 |
5 – 7,5 |
300 – 400 |
15 – 20 |
Springbok |
35 |
15 – 25 |
0,5 – 1 |
100 – 200 |
3,5 – 5,3 |
300 – 450 |
10 – 15 |
Steenbok |
12 |
15 – 25 |
0,2 – 0,3 |
100 – 200 |
1,2 – 2,4 |
300 – 450 |
4 – 6 |
Common Duiker |
15 |
15 – 25 |
0,2 – 0,4 |
100 – 200 |
1,5 – 3 |
150 – 300 |
2,2 – 4,5 |
Zebra |
250 |
15 – 25 |
4 – 6,5 |
400 – 500 |
100 – 150 |
300 – 500 |
90 – 150 |
Warthog |
80 |
40 – 60 |
3 – 7 |
200 – 300 |
16 – 22 |
300 – 500 |
24 - 40 |
ADMINISTRATION
Inject dose deep into a large muscle mass of the neck, shoulder, back or hindquarter. Intrathoracic, intra-abdominal or subcutaneous injection is to be avoided. Etorphine is commonly administered in combination with alpha-two agonists (xylazine, medetom- idine). The alpha-two pharmacodynamics lessen the “opiate rigidity” commonly seen when etorphine is given alone.
FDA Approved Presentation for Etorphine hydrochloride
Etorphine (M99) is approved in 1mg/ml strength in the United States. It is not currently commercially available due to lack of production by the manufacturer. Its approved form in South Africa is at the 4.9 and 9.8 mg/ml strengths (Captivon, Wildlife Pharma- ceuticals South Africa, Karino). Availability of the Immobilon product in the United Kingdom is unknown at this time.
Compounded Forms Possible
The routine concentrations compounded are 1 mg/ml and 10 mg/ml in a 10 ml vial.
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