Chemicals / Complex Chemical Agents/ Chemical:

Morphine (with special reference to Ruminants, Elephants, Bears, Lagomorphs, Ferrets and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary
Opiate analgesic. (B263)

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Names and Formulae
Type Opiate analgesic. (B263)
Alternative Names Morphine, 7,8-Didehydro-4,5-epoxy-17-methylmorphinnan-3,6-diol. (W324)
Chemical Formula C17H19NO3 (W324)
Chemical Structure --
Molecular Weight 285.342 (W324)
Related Chemicals --

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Physical Properties / Chemistry
Appearance

Morphine sulphate: white crystals, odourless. (B263)

Melting point --
Boiling point --
Density --
Water solubility Morphine sulphate: 62.5 mg/mL, i.e.1 g in 16 mL of water. (B263)
Other solubility
  • Morphine sulphate: 1.75 mg/mL of alcohol. (B263)
  • Morphine sulphate: Insoluble in chloroform. (B263)
  • Morphine sulphate: Insoluble in ether. (B263)
Acid/Base Morphine sulphate injection: pH range 2.5 to 6. (B263)

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Pharmacology & General Information
Pharmacology
  • Potent agonist, acting on the mu receptors, and perhaps also on the kappa and delta receptors. (B201.10.w10)
  • CNS effects caused by morphine are irregular and species specific. Horses, sheep, cattle, goats and swine may exhibit excitement after administration. (B263)
  • Horses, pigs and ruminants do not respond to emetic effects of morphine. (B263)
  • Hyperthermia may be seen in horses, cattle, goats and cats following administration of morphine. (B263)
Storage / Stability
  • Morphine gradually darkens in colour when exposed to light, therefore should not be stored under bright lights. (B263)
  • Morphine does not appear to adsorb to plastic or PVC syringes, tubing or bags. (B263)
Legal Category (In UK)
  • Controlled drug. (B201.10.w10)

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Penny Cusdin (V.w60)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications
Activity --
Appropriate Use
  • For severe pain. (B201.10.w10)
  • For the treatment of acute pain in dogs, cats, horses, swine, sheep and goats. (B263)
  • As a pre-anaesthetic agent in dogs and swine. (B263)
  • As an antitussive, antidiarrhoeal, and as an adjunctive therapy for some cardiac abnormalities in dogs. (B263)
Limitations
  • Not recommended in horses due to profound excitement it produces. (B201.10.w10)
Notes Laboratory Interactions:
  • May increase plasma amylase and lipase values for 24 hours after administration as morphine may raise biliary tract pressure. (B263)

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability

 

Distribution
  • Highest levels of morphine are found in the liver, kidney and lungs. Lower levels are found in the CNS. (B263)
  • The majority of free morphine is found in skeletal muscle. (B263)
  •  Morphine crosses the placenta, and will affect neonates if given to animals before giving birth. (B263)
  • Small amounts of morphine will be present in the milk of nursing mothers. (B263)
Plasma Protein binding / Storage --
Elimination Route
  • Metabolised by the liver, primarily by glucuronidation.  Metabolites are excreted by the kidneys. (B263)
Elimination half-life / Clearance Rate
  • In horses: Half life of 88 minutes after a dose of 0.1 mg/kg IV. (B263)
  • In cats: Half life of 3 hours. (B263)
  • In horses, after a dose of 0.1 mg/kg IV, morphine was detectable in the serum for 48 hours and in the urine for up to 6 days. (B263)
Drug Interactions
  • "Morphine sulphate is physically compatible at a concentration of 16.2 mg/l with the following intravenous fluids: Dextrose 2.5 %, 5 %, 10 % in water; Ringer's injection and Lactated Ringer's injection; Sodium Chloride 0.45% and 0.9 % for injection.  It is also physically compatible when mixed with: Atropine sulphate, benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, diphenhydramine HCl, pentazocine lactate, promazine HCl, scopolamine HBr, and succinylcholine chloride." (B263)
  • Morphine sulphate is physically incompatible with: "aminophylline, chlorothiazide sodium, heparin sodium, meperidine, pentobarbital sodium, phenobarbital sodium, phenytoin sodium, sodium bicarbonate, and thiopental sodium." (B263)
  • May interact with other CNS depressants, e.g. anaesthetics, antihistamines, phenothiazines, barbiturates, transquillisers, alcohol to cause increased CNS or respiratory depression. (B263)
  • Contraindicated in animals receiving MAO inhibitors (rarely used in animals). (B263)

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Administration
Formulations available UK
  • No veterinary preparations available. (B201.10.w10)
  • Human preparations:
    • Morphine Sulphate, Injection, morphine sulphate 10 mg/mL, 15 mg/mL, 20 mg/mL, 30 mg/mL. (B201.10.w10)
Doses / Administration Routes / Frequencies Note: no opiate is authorized for use in food-producing animals in the UK. (B217.69.w69)

Sheep:

Experimental data:

  • Morphine, used in sheep subjected to experimental surgery, required high doses and did not always produce obvious analgesia. (P61.62.w1)
Goats:
  • Up to 10 mg total, by intramuscular injection (as an analgesic). (B263)

Horses:

  • 0.22 mg/kg intramuscularly or slow intravenous injection. (B263)
  • 0.2 to 0.6 mg/kg intravenously (slowly); premedicate with xylazine (1 mg/kg IV) to reduce excitement. (B263)
  • 0.02 to 0.04 mg/kg intravenously. (B263)
  • 0.05 to 0.12 mg/kg intravenously. (B263)

Pre-treatment with acepromazine (0.02-0.04 mg/kg IV) or xylazine (0.3-0.5 mg/kg IV) may reduce excitement caused by the morphine. (B263)

Elephants:

  • For analgesia: 3.0 - 6.0 mg/100 kg bodyweight four times a day. (B10.49.w21)
  • For analgesia and sedation: 6.0 - 20.0 mg/kg bodyweight four times a day. (B10.49.w21)
Bears (Ursidae - Bears (Family)):
  • For analgesia: 0.1 - 0.5 mg/kg intramuscularly or intravenously every 2-4 hours, during surgery (Cholecystectomy in Bears). (V.w89, V.w90)
    • Note: in one bear, an apparent excitatory response to morphine resulted in abandonment of the planned surgical procedure. (V.w90)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 5 mg/kg subcutaneously. (B373.Guide.w41)
  • 2.0 - 5.0 mg/kg intramuscularly or subcutaneously every two to four hours. (B546, B601.15.w15)
  • 2.0 - 5.0 mg/kg subcutaneously or intramuscularly every two to four hours. (B602.41.w41)

Ferrets - Mustela putorius furo - Ferret:

  • 0.5 - 5.0 mg/kg subcutaneously or intramuscularly every two to six hours. (B602.41.w41)
  • 0.5 - 2.0 mg/kg every 12 - 24 hours. (B626.App.w22)
  • 0.1 mg/kg by epidural injection once for epidural anaesthesia/analgesia. (B631.22.w22)

Great Apes

  • Adult Pan troglodytes - Chimpanzee: 0.01 - 0.1 mg/kg intravenously. (W768.Jun2012.w1)
  • Primates: 1 - 2 mg/kg orally, intravenously, subcutaneously or intramuscularly every four hours. . (D425.3.15.w3o)
Monitoring parameters
  • Respiratory rate/depth. (B263)
  • CNS level of depression/excitement. (B263)
  • Blood pressure if possible and indicated (especially with IV use). (B263)
  • Analgesic activity. (B263)

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Withdrawal period / Withholding time
Notes Note: no opiate is authorized for use in food-producing animals in the UK. (B217.69.w69)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in animals with a head injury or raised intracranial pressure (B201.10.w10), and animals with acute abdominal conditions such as colic, as the effects of the drug may obscure diagnosis. (B263)
  • Contraindicated in animals sensitive to narcotic analgesics, or animals receiving MAO inhibitors. (B263)
  • Contraindicated in animals with diarrhoea caused by poisoning, until the toxin is eliminated from the GI tract. (B263)
  • Contraindicated in animals that have been stung by the scorpion species (Arachnida - Arachnids (Class)) Centruroides sculpturatus and C. gertschi, as morphine may potentiate the scorpion venom. (B263)
  • Extreme caution in patients with respiratory disease or dysfunction. (B263)
  • Use with caution in animals with hypothyroidism, severe renal insufficiency, adrenocortical insufficiency, and in old or extremely debilitated animals. (B263)
Adverse Effects / Side Effects / Warnings
  • Constriction of pupils (or dilatation in species that show excitability at moderate to high doses). (B201.10.w10)
  • Peripheral vasodilatation. (B201.10.w10)
  • Respiratory depression. (B201.10.w10)
  • Vomiting. (B201.10.w10)
  • Exaggerated spinal cord reflexes. (B201.10.w10)
  • Initial defecation, followed by constipation. (B201.10.w10)
  • Transient hypotension. (B201.10.w10)
  • Urine retention. (B201.10.w10)
  • Sweating in horses. (B201.10.w10)
  • Bradycardia, but high doses may cause tachycardia in horses and dogs. (B201.10.w10)
  • Respiratory depression in neonates if used in pregnant animals prior to birth. (B201.10.w10)
  • Hyperthermia in cattle, goats, horses and cats. (B263)
  • In bears (Ursidae - Bears (Family)): An apparent excitatory response to morphine has been seen in one bear. (V.w89, V.w90)
Operator Warnings --
Overdose / Acute Toxicity
  • Overdose may produce profound respiratory and/or CNS depression. Newborn animals are more susceptible than adults. (B263)
  • Other toxic effects include cardiovascular collapse and skeletal muscle hypotonia. (B263)
  • Horses, cats, cattle and swine may display excitement and seizures at high doses or if the drug is administered by rapid intravenous injection. (B263)
  • Naloxone may be used to treat respiratory depression in the event of a morphine overdose. Naloxone may need to be repeated several times. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment
Natural sources --
Human-associated sources --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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