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In the medical world, the advent of Xylazine as a recreational drug has caused great concern, especially in the UK where it has been connected to multiple deaths recently.

In order to help medical practitioners better understand and handle instances involving Xylazine, this article explores the pharmacological characteristics, effects, and medical consequences of the drug.

About Xylazine

Xylazine, an animal tranquilizer, is connected to overdose deaths and is becoming more and more prevalent in the illegal drug trade in the United States.

Xylazine was once created in 1962 as a sedative and analgesic for veterinarians, but some groups have since come to associate it with recreational drug use.

Its link to gory deaths that resemble the actions of flesh-eating zombies has scared medical professionals as well as public health officials.

It is not authorized for use in humans. Xylazine has the potential to be fatal, and it becomes even more so when mixed with opioids such as fentanyl.

The White House Office of National Drug Control Policy has designated fentanyl combined (adulterated) with xylazine as an emerging hazard due to its effect on the opioid crisis.

A National Response Plan was unveiled by the White House on July 11, 2023, in response to the growing threat posed by fentanyl combined with xylazine. 

Although it is not FDA-approved for usage in humans, xylazine is a non-opioid that is utilized as a muscle relaxant, sedative, anesthetic, and analgesic for animals.

Its strong CNS depressive effects led to its approval for non-human use.  

Xylazine is increasingly being discovered in the illicit drug supply, usually coupled with fentanyl. It has chemical features comparable to other medicines like clonidine and may have similar therapeutic effects.

When mixed with heroin or fentanyl, it's known as "tranq" or "tranq dope."

Studies have revealed that xylazine is frequently mixed with illegal opioids, such as fentanyl, and users claim to use fentanyl that has been mixed with xylazine to prolong the euphoric effects of the drug.

The majority of overdose deaths associated with xylazine and fentanyl also included the use of cocaine, heroin, alcohol, benzodiazepines, gabapentin, methadone, and prescription opioids.

Mechanism of Action

Xylazine mainly acts by agonizing α2-adrenergic receptors, which causes drowsiness and depression of the central nervous system.

It also prevents the release of norepinephrine, which causes bradycardia and hypotension. When abused, the drug's intensity and duration of action render it a deadly substance.

The findings of one research suggest that endogenous opioids and μ-opioid receptors play a role in the pain-relieving effects of xylazine in the central nervous system.

However, δ- and κ-opioid receptors seem unrelated to this effect. These results suggests of how xylazine, commonly used in veterinary medicine, alleviates pain centrally.

Xylazine acts fast, typically within minutes, and its effects can last over eight hours. After an overdose, symptoms may endure from 8 to 72 hours, varying widely.

Clinical Manifestations

Acute Xylazine poisoning manifests as a range of symptoms, from extreme hypotension and cardiovascular collapse to drowsiness and respiratory depression.

The most frequent adverse effects in people with intoxications are:¹

• Coma

• Diabetes

• Acidemia

• Hypotonia

• Dry mouth

• Bradycardia

• Hypotension

• Urinary incontinence

• Miosis (constricted pupils)

• Decrease in cardiac output

• Premature ventricular contraction

• Nonspecific ECG ST-segment changes

• Temporary hypertension due to vagus nerve stimulation

Notably, severe tissue necrosis is one of its "flesh-eating" effects, frequently requiring surgical intervention.

Xylazine causes skin abscesses and ulcers due to its vasoconstricting effect on blood vessels, reducing skin oxygen levels.

Chronic use worsens this, leading to severe infections and impaired wound healing.

Alterations in mental status, including disorientation and delusions, could potentially transpire.

Medical Implications

In patients presenting with unexplained tissue necrosis, healthcare practitioners should be on the lookout for signs of Xylazine poisoning, especially when polysubstance addiction is present.

Improving patient outcomes requires early detection and supportive therapy, such as hemodynamic support, airway management, and surgical debridement.

In instances of suspected xylazine overdose, it's important to promptly administer naloxone and position the individual in the recovery stance to ensure airway safety.

The recovery position involves rolling them onto their side, tilting the head back, and monitoring for airway obstruction. Presently, there isn't an FDA-approved antidote for xylazine intoxication.

Treatment focuses on supportive care, including oxygen, fluids, vasopressors, electrolyte balance, and glucose control. Avoiding CNS depressants is suggested.

Opioid toxicity is treated with naloxone. The possibility of thromboembolism and extended sedation should be looked for.

Due to its lipophilic nature, hemodialysis might not be able to completely remove xylazine.

As xylazine is not an opioid, naloxone may not fully reverse a xylazine-associated opioid overdose because xylazine effects may linger even after opioid reversal.

While evidence is limited, considering dexmedetomidine or clonidine as adjunctive therapy for managing agitation in xylazine withdrawal could be reasonable due to their similar mechanisms of action.

Xylazine detected in 42 Connecticut deaths, March-August 2019. Mixed with opioids or stimulants alters drug toxicity.

Detecting aids distinguishing illicit from prescribed fentanyl, helps track illegal drugs, and requires caution in emergency treatment as it doesn't respond to naloxone.

Conclusion

The concerning surge in deaths linked to Xylazine highlights the necessity for healthcare practitioners to exercise greater caution and awareness.

Through a comprehensive comprehension of the pharmacological characteristics, clinical presentations, and suitable therapeutic approaches, medical professionals can proficiently tackle the obstacles presented by this drug that consumes flesh.

1  Common Adverse effects