Xylazine Trade names Rompun, Anased, Sedazine, Chanazine
Routes of administration By mouth, inhalation, or injection (intravenous, intramuscular, or subcutaneous)
Xylazine is a structural analog of clonidine and an α2-adrenergic receptor agonist, sold under many trade names worldwide.
Xylazine is a common veterinary drug used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle, and other mammals.
In veterinary anesthesia, it is often used in combination with ketamine.
Veterinarians also use xylazine as an emetic, especially in cats.
Xylazine has become a commonly abused street drug in the United States where it is known by the street name “tranq”.
The drug is being diverted from stocks for equine veterinarians as well as trafficked in bulk from China to be used as a cutting agent for heroin and fentanyl, causing necrotic skin wounds leading to serious infections and limb amputations as well as other health issues.
Fentanyl mixed with xylazine is known by the street names “sleep-cut”, “zombie drug”, “Iso” and “tranq dope”.
Xylazine has several central nervous system depressant effects.
Xylazine administration is used for sedation, anesthesia, muscle relaxation, and analgesia.
It causes a significant reduction in blood pressure and heart rate in healthy volunteers.
Xylazine use in human beings associated with hypotension and bradycardia, it therefore was not approved by the Food and Drug Administration (FDA) for human use.
Xylazine was approved by the FDA only for veterinary use as a sedative, analgesic, and muscle relaxant in dogs, cats, horses, elk, fallow deer, mule deer, sika deer, and white-tailed deer.
The sedative and analgesic effects of xylazine are related to central nervous system depression.
Xylazine’s muscle relaxant effect inhibits the transmission of neural impulses in the central nervous system.
Xylazine is a component of the most common anesthetic, ketamine-xylazine .
It is frequently used in the treatment of tetanus.
It is not used in human medical treatment.
Xylazine is similar to drugs such as phenothiazines, tricyclic antidepressants, and clonidine.
As an anesthetic, it is typically used in conjunction with ketamine.
In animals, xylazine may be administered intramuscularly or intravenously.
Xylazine is typically only administered once for intended effect before or during surgical procedures.
α2-Adrenergic receptor antagonists such as atipamezole and yohimbine may be used to reverse the effects of xylazine in animals.
Side effects in animals include transient hypertension, hypotension, and respiratory depression.
It decreases of tissue sensitivity to insulin leads to xylazine-induced hyperglycemia and a reduction of tissue glucose uptake and utilization.
The effects in animals last up to 4 hours.
In dogs, sheep, horses, and cattle, the half-life is very short: only 1.21– 5.97 minutes.
The half life depends on the age of the animal, as age is related to prolonged duration of anesthesia and recovery time.
Toxicity occurs with repeated administration, given that the metabolic clearance of the drug is usually calculated as 7– 9 times the half-life, which is 4 to 5 days for the clearance of xylazine.
It has a highly lipophilic nature, it directly stimulates central α2-adrenergic receptors as well as peripheral α-adrenergic receptors in a variety of tissues.
As an agonist, xylazine reduces release of norepinephrine and dopamine in the central nervous system.
It does so by mimicking norepinephrine in binding to pre-synaptic surface autoreceptors, which leads to feedback inhibition of norepinephrine release.
Xylazine also serves as a transport inhibitor by suppressing norepinephrine transport function through competitive inhibition of substrate transport.
Xylazine’s chemical structure closely resembles clonidine.
Xylazine is absorbed, metabolized, and eliminated rapidly.
Xylazine can be inhaled or administered intravenously, intramuscularly, subcutaneously, or orally either by itself or in conjunction with other anesthetics, such as ketamine, barbiturates, chloral hydrate, and halothane in order to provide reliable anesthesia effects.
The most common route of administration is parenteral.
Xylazine’s action can be seen usually 15–30 minutes after administration and the sedative effect may continue for 1–2 hours and last up to 4 hours.
When xylazine gains access to the vascular system, it enters the heart, lungs, liver, and kidney, and penetrates the blood–brain barrier, due to the uncharged, lipophilic nature of the compound.
Xylazine is metabolized by liver cytochrome P450 enzymes.
When it reaches the liver, xylazine is metabolized and proceeds to the kidneys to be excreted in urine.
Around 70% of a dose is excreted by urine.
Thus, urine can be used in detecting xylazine administration because it contains many metabolites, which are the main targets and products in urine.
Within a few hours, xylazine decreases to undetectable levels.
Other factors can impact the pharmacokinetics of xylazine, such as sex, nutrition, environmental conditions, and prior diseases.
Xylazine is not regulated as a controlled substance under the Controlled Substances Act.
It is sold online through distributors often without requiring proof of a veterinary license.
As a commonly used veterinary medicine xylazine is diverted from veterinary sources.
Its low price makes it attractive for dealers looking for a cheap additive that is addictive and not treatable with opiate withdrawal medications.
The withdrawal can last for two weeks.
Xylazine is most commonly ingested as an additive with fentanyl.
Xylazine and heroin trigger similar behavioral outcomes, the former is often secretly mixed into illegal doses of heroin.
The combination of heroin and xylazine produces a potentially more deadly high than administration of heroin alone.
Xylazine is also frequently found in “speedball”, a mixture of a stimulant drug such as cocaine with a depressant drug such as heroin, morphine and/or fentanyl.
As of May 2024, over 90% of illegally purchased opiates were adulterated with Xylazine in Philadelphia, and Massachusetts, the percentage of samples containing xylazine increased to 42%.
Xylazine overdose is often fatal in humans.
The most common side-effects in humans associated with xylazine administration include bradycardia, respiratory depression, hypotension, transient hypertension secondary to α1-adrenergic receptor stimulation, and other central and hemodynamic changes.
Xylazine administration can lead to diabetes mellitus and hyperglycemia, and other possible side-effects are areflexia, asthenia, ataxia, blurred vision, disorientation, dizziness, drowsiness, dysarthria, dysmetria, fainting, hyporeflexia, slurred speech, somnolence, staggering, coma, apnea, shallow breathing, sleepiness, premature ventricular contraction, tachycardia, miosis and dry mouth.
Rarely, hypotonia, urinary incontinence, and nonspecific electrocardiographic ST segment changes occur.
Following an overdose, symptoms can last for 8–72 hours.
Chronic intravenous use of xylazine with opioids is reported to be associated with muscle atrophy, physical deterioration, dependence, abscesses, and skin ulceration, possible necrosis with eschar formation, which can be physically debilitating and painful.
Hypertension followed by hypotension, bradycardia, and respiratory depression can lower tissue oxygenation in the skin.
Its chronic use of can progress the skin oxygenation deficit, leading to severe skin ulceration.
Lowered skin oxygenation is associated with impaired healing of wounds and a higher chance of infection.
The ulcers may ooze pus.
uUlcers may have a characteristic odor.
In severe cases, surgical amputations must be performed on the affected limbs..
Since xylazine is not an opioid, it cannot be neutralized by naloxone (Narcan).
Human tolerance to xylazine varies widely, with toxicity and fatality occurring between doses of 40–2,400 mg.
There is no defined safe or fatal concentration of xylazine because of the significant overlap between the non-fatal and postmortem blood concentrations of xylazine.
There is no specific antidote to treat humans who overdose on xylazine.
Hemodialysis has been suggested as a form of treatment, but is usually unfavorable due to the large volume of distribution of xylazine.
Detection of xylazine in humans involves various screening methods: urine screenings, thin layer chromatography (TLC), gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry.
The treatment after a xylazine overdose primarily involve maintaining respiratory function and blood pressure.
In cases of intoxication, physicians recommend intravenous fluid infusion, atropine, and hospital observation.
Severe cases may require tracheal intubation, mechanical ventilation, gastric lavage, activated charcoal, bladder catheterization, electrocardiographic (ECG) and hyperglycemia monitoring.