Yohimbine Hydrochloride

Alpha-2 adrenergic antagonist Indole alkaloid

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 0.1 mg/kg (for xylazine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: For medetomidine reversal, dose may be 0.1 mg/kg IV; for oral use, 0.5-1 mg/kg has been used but is not common.
Cat IV 0.1 mg/kg (for xylazine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: For medetomidine reversal, dose may be 0.1 mg/kg IV; oral use not recommended.
Horse IV 0.03-0.05 mg/kg (for xylazine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: For detomidine reversal, dose may be 0.03 mg/kg IV.
Cattle IV 0.125 mg/kg (for xylazine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: For xylazine reversal in cattle, dose is typically 0.125 mg/kg IV.
Sheep and Goats IV 0.1-0.2 mg/kg (for xylazine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: Dose may vary; use lower end for goats.
Rabbit IV 0.2 mg/kg (for medetomidine reversal) Slow IV injection, may repeat if needed Duration: Single dose or as needed
Notes: For medetomidine reversal, dose is typically 0.2 mg/kg IV.
Birds IV or IM 0.1-0.2 mg/kg (for xylazine reversal) Single dose Duration: Single dose
Notes: Dose may vary by species; use caution in small birds.

Clinical Indications & Species Uses

General Indications
  • Reversal of alpha-2 adrenergic agonist-induced sedation and analgesia
Dog (Canine)
  • Reversal of sedation and effects of alpha-2 agonists (e.g., xylazine, medetomidine)
  • Treatment of xylazine overdose
  • Aid in diagnosis of pheochromocytoma (as a provocative test, though rarely used)
Cat (Feline)
  • Reversal of sedation and effects of alpha-2 agonists (e.g., xylazine, medetomidine)
Horse (Equine)
  • Reversal of sedation and effects of alpha-2 agonists (e.g., xylazine, detomidine)
Cattle (Bovine)
  • Reversal of sedation and effects of alpha-2 agonists (e.g., xylazine)
Small Ruminants (Sheep / Goat)
  • Reversal of sedation and effects of alpha-2 agonists (e.g., xylazine) in sheep and goats
Rabbit & Small Mammals
  • Reversal of sedation and effects of alpha-2 agonists (e.g., medetomidine) in rabbits
Avian & Poultry
  • Reversal of sedation and effects of alpha-2 agonists in some avian species (e.g., xylazine, medetomidine)
Exotic & Other Species
  • Reversal of sedation and effects of alpha-2 agonists in various exotic species (e.g., reptiles, small mammals)

Pharmacology & Mechanism of Action

Drug Class: Alpha-2 adrenergic antagonist | Pharmacological Group: Indole alkaloid

Mechanism of Action: Yohimbine is a selective competitive antagonist at alpha-2 adrenergic receptors, with a higher affinity for alpha-2 than alpha-1 receptors. It blocks the central and peripheral effects of alpha-2 agonists such as xylazine, medetomidine, and detomidine. By antagonizing these receptors, yohimbine reverses sedation, analgesia, and other effects mediated by alpha-2 agonism. It also has some antagonistic activity at serotonin receptors and may have weak monoamine oxidase inhibitory effects.

Pharmacodynamics: Yohimbine reverses the sedative, analgesic, and cardiorespiratory depressant effects of alpha-2 agonists. It increases sympathetic outflow, leading to increased heart rate, blood pressure, and alertness. It also stimulates the central nervous system and may cause behavioral arousal. In addition, yohimbine has been used as a local anesthetic and has been studied for its effects on erectile dysfunction, but these are not primary veterinary uses.

⚑ Pharmacokinetics Summary

Absorption: Yohimbine is well absorbed after oral administration, but bioavailability may be variable due to first-pass metabolism. Onset of action after IV administration is rapid (within minutes).
Distribution: Yohimbine is widely distributed in the body, crosses the blood-brain barrier, and has a large volume of distribution. It is highly lipid-soluble.
Metabolism: Yohimbine is extensively metabolized in the liver, primarily by oxidation and conjugation. Metabolites are excreted in urine.
Excretion: Yohimbine and its metabolites are excreted primarily in urine, with some elimination in feces. The elimination half-life is relatively short in most species.
Half-Life: Dogs: approximately 15-30 minutes (IV); Horses: approximately 30-60 minutes (IV); Cattle: approximately 30 minutes (IV).
Bioavailability: Oral bioavailability is low and variable (approximately 5-20% in dogs) due to extensive first-pass metabolism.
Protein Binding: Approximately 82-90% bound to plasma proteins.

Available Formulations & Strengths

Injectable Solution 2 mg/mL (as hydrochloride) (IV, IM)
Oral Tablet 5.4 mg (as yohimbine hydrochloride) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to yohimbine
  • Severe cardiovascular disease (e.g., hypertension, arrhythmias)
  • Concurrent use with monoamine oxidase inhibitors (MAOIs)
  • Use in animals with a history of seizures or CNS disorders
  • Do not use in animals with glaucoma or prostatic enlargement (due to potential exacerbation)
Warnings & Clinical Precautions:
  • Use with caution in animals with renal or hepatic impairment
  • May cause transient hypertension and tachycardia; monitor cardiovascular status
  • In horses, may cause excitement and ataxia if given too rapidly
  • In cattle, may cause agitation and increased motor activity
  • Not for use in animals intended for breeding unless specifically indicated
  • Use with caution in geriatric or debilitated animals
  • May cause vomiting in some species (especially cats and dogs) when given rapidly IV
  • In food animals, observe withdrawal times

Adverse Effects & Reactions

Common:

  • Tachycardia
  • Hypertension
  • Excitement
  • Tremors
  • Vomiting
  • Salivation

Serious / Severe:

  • Arrhythmias
  • Seizures
  • Severe hypertension
  • Pulmonary edema (rare)
  • Cardiovascular collapse (overdose)

Rare:

  • Allergic reactions
  • Hepatotoxicity (with chronic use)
  • Local irritation at injection site

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Alpha-2 agonists (e.g., xylazine, medetomidine) Yohimbine antagonizes the effects of alpha-2 agonists; used for reversal. Moderate
Monoamine oxidase inhibitors (MAOIs) Risk of hypertensive crisis due to additive sympathomimetic effects. High
Tricyclic antidepressants May potentiate cardiovascular effects and risk of arrhythmias. Moderate
Sympathomimetic agents (e.g., epinephrine) Additive pressor effects, increased risk of hypertension and arrhythmias. High
Antihypertensive drugs (e.g., clonidine) Yohimbine may counteract the effects of antihypertensive agents. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypertension
  • Tachycardia
  • Arrhythmias
  • Seizures
  • Hyperthermia
  • Respiratory depression
  • Cardiovascular collapse

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Administer IV fluids to maintain blood pressure and tissue perfusion. Use antihypertensive agents (e.g., nitroprusside, phentolamine) if severe hypertension occurs. Control seizures with diazepam or barbiturates. Monitor cardiac function and treat arrhythmias as needed. In cases of recent oral ingestion, consider gastric lavage and activated charcoal.

Food Animal Withdrawal Times

πŸ₯© Meat: 3 daysπŸ₯› Milk: 3 days

Withdrawal times are not well established for yohimbine in food animals. A conservative withdrawal period of at least 3 days for meat and milk is recommended. For eggs, no data available; avoid use in laying hens if possible.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C, excursions permitted to 15-30Β°C).

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; available as a generic drug for human use and compounded for veterinary use.

Extra-Label (Off-Label) Use: In the US, yohimbine is not FDA-approved for veterinary use, but it is commonly used in an extra-label manner under AMDUCA. Extra-label use requires a valid veterinarian-client-patient relationship and must comply with regulations, including withdrawal times for food animals.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Yohimbine is primarily used in veterinary medicine to reverse the effects of alpha-2 adrenergic agonists such as xylazine, medetomidine, and detomidine. It is most effective when administered intravenously, and the dose should be adjusted based on the specific alpha-2 agonist used and the species. Rapid administration can cause excitement and cardiovascular effects, so slow IV injection is recommended. In emergency situations, yohimbine can be life-saving. However, it is not a specific antidote for all sedatives and should not be used to reverse other classes of drugs. Always monitor animals closely after administration, as re-sedation can occur if the alpha-2 agonist has a longer duration of action than yohimbine. In food animals, observe appropriate withdrawal times. Yohimbine should be used with caution in animals with cardiovascular disease, and its use in pregnant animals should be avoided unless the benefits outweigh the risks.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)