Tramadol

(tramadol hydrochloride)

Brand

Ultram, Tramal

Availability

  • Tablets: 50 mg
  • Suspension: may be compounded from tablets
  • Injectable: 50 mg/mL (U.K.)

Pharmacology

Tramadol hydrochloride is a synthetic, centrally acting, opiate agonist analgesic with a dual mode of action. It binds to opioid receptors modifying the transmission of pain impulses, and inhibits the reuptake of serotonin and norepinephrine. The efficacy and potency of tramadol is only five to ten times lower than that of morphine (Giusti et al, 1997). As of 2014 tramadol is now classified as a narcotic analgesic, and placed as a scheduled controlled substance by the U.S. FDA.

Tramadol has been shown to cause less respiratory depression and sedative effects than morphine. It also appears to have no effect on heart rate, left ventricular function, or cardiac index at dosages which are therapeutic. Unlike morphine, tramadol has not been shown to cause histamine release.

When given orally tramadol is almost completely absorbed. Rate and extent of absorption when given orally is not appreciably affected by the presence of food.

Distribution of tramadol in rats has been shown to cross the blood-brain barrier, as well as, crossing the placenta and being distributed in breast milk in small amounts. Although studies have shown both embryo and fetal toxicity, in rats, 3 to 15 times above the maximum human dose. At this time it is advised to refrain from use in pregnant and nursing rats, unless benefit outweighs risk as assessed by veterinarian.

Tramadol is metabolized in the liver and excreted by the kidneys, with 52% of the drug unchanged, in dogs and rats.

Indications

Used for moderate to moderately severe post-op or injury-related pain, or where pain is present in chronic or terminal illness.

Drug Interactions or Contraindications

  • Tramadol should not be co-administered with selegiline or any other psychoactive class of medication such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (e.g., Clomicalm), monoamine oxidase inhibitors, other narcotic pain medicine, or tranquilizers (e.g., diazepam).
  • Consult veterinarian if co-administering with herbal medicines.
  • In animal studies, naloxone administration following Tramadol may potentiate the risk of convulsions.

Adverse Reactions

CNS: sedation can occur at higher than therapeutic dosages.

CV: bradycardia (decreased heart rate).

Resp: decreased respiratory rate at higher than therapeutic dosages.

GI: upset stomach (noted by signs of pica), constipation, and loss of appetite will cease when drug discontinued.

Skin: itching.

*Note: In case of an overdose, signs that may appear include: respiratory depression, mental alteration, pinpoint pupils and seizures. Treatment for overdose is supportive care.

Dosage Recommendations

In animals, tramadol is removed from the body via liver and kidney excretion. Rats suffering from diseases in these systems should be monitored by a veterinarian, as it may be necessary to adjust the dose.

*Note: tramadol dosage used in rats was initially empirical, and based on published dog/cat dosages. 27. It has since been given recognized published dosing for rats.*

1 mg/kg to 4 mg/kg, PO, SQ, BID  30. Dosage range used successfully in pet rats by Anthony Pilny, DVM, DABVP.

or

5 mg/kg, IM  34

or

5 mg/kg to 20 mg/kg, PO, SQ, q12hr to q24hr  34, 35, 41

or

10 mg/kg to 20 mg/kg, PO, SQ, q8hr to q12hr  42

Dosage to be used is based upon type and extent of pain involved. Use the lowest dose for condition being treated which achieves the desired effect.

Considerations

  • Tramadol can be used separately or in combination with steroidal or nonsteroidal anti-inflammatory drugs where deemed appropriate by the veterinarian. May also be combined with gabapentin. 42
  • Oral dosing can be given with or without food; however, tramadol has a mildly bitter taste and mixing with something flavored will make it more palatable to the rat.
  • Tablets should be stored in an airtight container at room temperature away from light.


Cross-references

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