General pharmacology


Common sedatives include alpha-2 adrenergic agents, benzodiazepines, phenothiazines and occasionally other drug classifications by species or age group.

Alpha adrenergic receptor agonists

Small animal drugs in this class included medetomidine and dexemedetomidine. While those can be used in LA species, we commonly use xylazine, detomidine and romifidine. These drugs reliably cause sedation and skeletal muscle relaxation; these drugs are often the only sedative needed. Most have a dose dependent effect (more drug = more sedation); however detomidine has a ceiling effect in horses where more drug stops causing more sedation and switches to causing longer duration sedation. Due to the alpha-1 effects that they also carry, these drugs do affect the heart and blood pressure. Hence, alpha adrenergic receptor agonists cause significant decreases in cardiac output along with vasodilation and hypotension.

As each drug has a different balance of alpha-1 and alpha-2 activities, side effects vary by drug and by species. These are notable concerns to keep in mind:

  • these drugs can cause first or second degree heart block – auscultate the heart before administering!
  • these drugs cause pulmonary resistance and sometimes fatal pulmonary edema in sheep; don’t use in sheep if it can be avoided
  • cattle are very sensitive to xylazine and require only 1/10 of the equine dose; they are NOT more sensitive to detomidine
  • xylazine causes uterine contractions and can lead to abortion in cattle in the third trimester; xylazine also makes Csections harder
  • xylazine causes glucosuria and increased urine production; this can be bad if your patient can’t urinate (urolithiasis)
  • xylazine causes vomiting in pigs and is not as useful as in other species
  • xylazine impairs cardiac output significantly in neonates (slows heart rate and neonates cannot adjust stroke volume); do not use in neonates


Xylazine in horses causes them to shift their weight to their front legs and numbs their neurons. This means they tend to kick without thinking and can kick easily due to the weight shift. Do not use xylazine alone as a sedative for any rear end procedures in horses. When combined with butorphanol, it is safe due to a more balanced weight distribution. Detomidine is also okay to use for hindlimb procedures due to the more balanced weight distribution.

Xylazine does not cause this weight redistribution in cattle.

The alpha-2 agents can be reversed with drugs such as atipamezole.

When combined with narcotics, the drugs are synergistic. The sedation is more profound as is the analgesia. Common combinations are xylazine +butorphanol (horses, cattle) or detomidine + butorphanol (horses).

Xylazine is being mixed with street drugs and is causing human deaths. Expect regulations on its use to be forthcoming.

Phenothiazine derivatives

Acepromazine is currently the main LA drug in this class. Typically administered parenterally (iv, sq or im), it leads to calming and muscle relaxation but no analgesia. It has a very prolonged onset of action but then persists for several hours. Assume it will take at least 20 minutes to take effect, regardless of route administered. If startled, the effect of the acepromazine can be overridden (animals are easily aroused).

These drugs also have anti-emetic and anti-arrhythmic effects.

The drugs are synergistic with opioids (neuroleptanalgesia) and the combination results in enhanced analgesia and enhanced sedation. Cattle respond well to an acepromazine + morphine combination.

Acepromazine cannot be reversed.

Side effects

  • stallions can develop priapism (persistent erections) that can lead to infertility; avoid in stallions
  • bulls develop penile relaxation but are not at risk of infertility unless the penis is traumatized while exposed. (The exposure is handy for penile surgery.)
  • severe hypotension occurs in sick animals and neonates; avoid in sick animals
  • many animals develop a temporarily lowered hematocrit due to splenic sequestration of red blood cells


The common LA drugs in this class are diazepam and midazolam. They are generally used interchangeably with midazolam used more commonly due to the higher cost of diazepam. Zolazepam is part of the drug combination Telazol (tiletamine/zolazepam).

The benzodiazepines are calming agents as well as anticonvulsants, appetite stimulants and skeletal muscle relaxants. The calming effect works best in neonates, geriatric and sick patients. The drugs tend to have minimal effects in healthy adults and/or can actually lead to paradoxical excitement.

These drugs are most often part of a general anesthesia protocol. As sedatives, benzodiazepines are primarily used in neonates when the alpha-2 adrenergic agonists would be too dangerous.

If diazepam is used, it is important to remember that diazepam binds to plastics and cannot be left in syringes or it will deactivate. Diazepam also tends to precipitate out when mixed with other drugs. It can be mixed with ketamine.

Diazepam should also only be given iv while midazolam can be given im.

Other drugs

In some species and age groups, butorphanol and ketamine can also be sedatives. In other species and age groups, they can lead to excitement rather than sedation. Be careful and do your research before using.

  • Butorphanol and other narcotics cause excitement in horses; do not use unless the horse is sedated (give the sedative first; let it work before giving the narcotic).
    • Neonatal foals do get sedated rather than excited
  • Butorphanol can cause excitement in calves but to a lesser degree; we can administer the sedative at the same time as butorphanol
  • Ketamine causes excitement in horses but can cause sedation in cattle
  • Camelids may or may not sedate with butorphanol. Blindfolding may help enhance the sedative effects

See the subsequent chapters for more details


Veterian key – sedatives and tranquilizers- nice cross species comparison



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Large Animal Surgery - Supplemental Notes Copyright © by Erin Malone, DVM, PhD is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.