Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

XYLAZINE HCL

Chemistry - Xylazine HCl is a alpha2-adrenergic agonist structurally related to clonidine. The pHof the commercially prepared injections is approximately 5.5. Dosages and bottle concentrations areexpressed in terms of the base.

Storage, Stability, Compatibility

Do not store above 30°C (86°F). Xylazine is reportedly compatible in the same syringe with several compounds, including: acepromazine, buprenorphine, butorphanol, chloral hydrate, and meperidine.

Pharmacology - XYLAZINE HCL

A potent alpha2-adrenergic agonist, xylazine is classified as a sedative/analgesicwith muscle relaxant properties. Although xylazine possesses several of the same pharmacologicactions as morphine, it does not cause CNS excitation in cats, horses or cat le, but causes sedationand CNS depression. In horses, the visceral analgesia produced has been demonstrated to besuperior to that produced by meperidine, butorphanol or pentazocine.
Xylazine causes skeletal muscle relaxation through central mediated pathways. Emesis is oftenseen in cats, and is also seen occasionally in dogs receiving xylazine. While thought to be centrallymediated, neither dopaminergic blockers (e.g., phenothiazines) or alpha-blockers (yohimbine, tolazoline) block the emetic effect. Xylazine does not cause emesis in horses, cattle, sheep or goats.
Xylazine depresses thermoregulatory mechanisms and either hypothermia or hyperthermia is apossibility depending on ambient air temperatures.
Effects on the cardiovascular system include an initial increase in total peripheral resistance withincreased blood pressure followed by a longer period of lowered blood pressures (below baseline).
A bradycardic effect can be seen with some animals developing a second degree heart block orother arrhythmias. An overall decrease in cardiac output of up to 30% may be seen. Xylazine hasbeen demonstrated to enhance the arryhthmogenic effects of epinephrine in dogs with or withoutconcurrent halothane.
Xylazine's effects on respiratory function are usually clinically insignificant, but at high dosages, it can cause respiratory depression with decreased tidal volumes and respiratory rates and an overalldecreased minute volume. Brachycephalic dogs and horses with upper airway disease may developdyspnea.
Xylazine can induce increases in blood glucose secondary to decreased serum levels of insulin. Innon-diabetic animals, there appears to be little clinical significance associated with this effect.
In horses, sedatory signs include a lowering of the head with relaxed facial muscles and droopingof the lower lip. The retractor muscle is relaxed in male horses, but unlike acepromazine, no reportsof permanent penile paralysis has been reported. Although, the animal may appear to be thoroughlysedated, auditory stimuli may provoke arousal with kicking and avoidance responses.
With regard to the sensitivity of species to xylazine definite differences are seen. Ruminants areextremely sensitive to xylazine when compared with horses, dogs, or cats. Ruminants generallyrequire approximately 1/10th the dosage that is required for horses to exhibit the same effect. Incattle (and occasionally cats and horses), polyuria is seen following xylazine administration, probably as a result of decreased production of vasopressin (anti-diuretic hormone, ADH).
Bradycardia and hypersalivation are also seen in cat le and are diminished by pretreating with atropine. Swine, require 20-30 times the ruminant dose and therefore, xylazine is not routinely usedin this species.
Uses, Indications - Xylazine is approved for use in dogs, cats, horses, deer, and elk. It is indicatedin dogs, cats and horses to produce a state of sedation with a shorter period of analgesia, and as apreanesthetic before local or general anesthesia. Because of the emetic action of xylazine in cats, itis occasionally used to induce vomiting after ingesting toxins.

Pharmacokinetics - XYLAZINE HCL

Absorption is rapid following IM injection, but bioavailabilities are incomplete and variable. Bioavailabilities of 40-48% in the horse, 17-73% in the sheep, and 52-90% in thedog have been reported after IM administration.
In horses, the onset of action following IV dosage occurs within 1-2 minutes with a maximumeffect 3-10 minutes after injection. The duration of effect is dose dependent but may last for approximately 1.5 hours. The serum half-life after a single dose of xylazine is approximately 50minutes in the horse and recovery times generally take from 2-3 hours.
In dogs and cats, the onset of action following an IM or SQ dose is approximately 10-15 minutes, and 3-5 minutes following an IV dose. The analgesic effects may persist for only 15-30 minutes, but the sedative actions may last for 1-2 hours depending on the dose given. The serum half-live ofxylazine in dogs has been reported as averaging 30 minutes. Complete recovery after dosing maytake from 2-4 hours in dogs and cats.
Xylazine is not detected in milk of lactating dairy cat le at 5 & 21 hours post-dose, but the FDAhas not approved the use of this agent in dairy cat le and no meat or milk withdrawal times havebeen specified.
Contraindications/Precautions - Xylazine is contraindicated in animals receiving epinephrine orhaving active ventricular arrhythmias. It should be used with extreme caution in animals withpreexisting cardiac dysfunction, hypotension or shock, respiratory dysfunction, severe hepatic orrenal insufficiency, preexisting seizure disorders, or if severely debilitated. Because it may inducepremature parturition, it should generally not be used in the last trimester of pregnancy, particularlyin cattle.
Be certain of product concentration when drawing up into syringe, especially if treating ruminants.
Do not give to ruminants that are dehydrated, have urinary tract obstruction, or are debilitated. It isnot approved for any species to be consumed for food purposes.
Horses have been known to kick after a stimulatory event (usually auditory); use caution. Avoidintra-arterial injection; may cause severe seizures and collapse. The manufacturers warn againstusing in conjunction with other tranquilizers.

Adverse Effects, Warnings

Emesis is generally seen within 3-5 minutes after xylazine administration in cats and occasionally in dogs. To prevent aspiration, do not induce further anesthesia untilthis time period has lapsed. Other adverse effects listed in the package insert (Gemini®, Butler) fordogs and cats include: muscle tremors, bradycardia with partial A-V block, reduced respiratory rate, movement in response to sharp auditory stimuli, and increased urination in cats.
Dogs may develop bloat from aerophagia which may require decompression. Because of gaseousdistention of the stomach, xylazine's use before radiography can make test interpretation difficult.
Adverse effects listed in the package insert (AnaSed®, Lloyd) for horses include: muscle tremors, bradycardia with partial A-V block, reduced respiratory rate, movement in response to sharpauditory stimuli, and sweating (rarely profuse). Additional y, large animals may become ataxicfollowing dosing and caution should be observed.
Adverse reactions reported in cattle include salivation, ruminal atony, bloating and regurgitation, hypothermia, diarrhea, and bradycardia. The hypersalivation and bradycardia may be alleviated bypretreating with atropine. Xylazine may induce premature parturition in cattle.
Overdosage - In the event of an accidental overdosage, cardiac arrhythmias, hypotension, andprofound CNS and respiratory depression may occur. Seizures have also been reported afteroverdoses. There has been much interest in using alpha-blocking agents as antidotes or reversalagents to xylazine. Yohimbine or tolazoline have been suggested to be used alone and in combination to reverse the effects of xylazine or speed recovery times. A separate monograph foryohimbine is available which discusses suggested doses, etc.
To treat the respiratory depressant effects of xylazine toxicity, mechanical respiratory support withrespiratory stimulants (e.g., doxapram) have been recommended for use.

Drug Interactions

The use of epinephrine with & without the concurrent use of halothaneconcomitantly with xylazine may induce the development of ventricular arrhythmias.
The combination use of acepromazine with xylazine is generally considered to be safe, but thereis potential for additive hypotensive effects and this combination should be used cautiously inanimals susceptible to hemodynamic complications.
Other CNS depressant agents (barbiturates, narcotics, anesthetics, phenothiazines, etc.)may cause additive CNS depression if used with xylazine. Dosages of these agents may need to bereduced.
A case report of a horse developing colic-like symptoms after reserpine and xylazine has beenreported. Until more is known about this potential interaction, use together of these two agentstogether should be avoided.
The manufacturers warn against using xylazine in conjunction with other tranquilizers.

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