Chemistry - An alpha adrenergic blocking agent, tolazoline HCl is structurally related to phentolamine. It occurs as a white to off-white, crystalline powder possessing a bitter taste and a slight aromatic odor. Tolazoline is freely soluble in ethanol or water. The commercially available (human) injection has pH between 3 and 4.
Storage/Stability/Compatibility - Commercially available injection products should be stored between 15-30°C and protected from light. The drug is reportedly physically compatible with the commonly used IV solutions.
Pharmacology - By directly relaxing vascular smooth muscle, tolazoline has peripheral vasodilating effects and decreases total peripheral resistance. Tolazoline also is a competitive alpha1 and alpha2 adrenergic blocking agent, explaining its mechanism for reversing the effects of xylazine. Tolazoline is rapid acting (usually within 5 minutes of IV administration), but has a short duration of action and repeat doses may be required.
Uses/Indications - Tolazoline is approved and indicated for the reversal of effects associated with xylazine in horses. It has also been used for this purpose in a variety of other species as well, but less safety and efficacy data is available.
In humans, the primary uses for tolazoline are: treatment of persistent pulmonary hypertension in newborns, adjunctive treatment and diagnosis of peripheral vasospastic disorders and as a provocative test for glaucoma after subconjunctival injection.
Pharmacokinetics - After IV injection in horses, tolazoline is widely distributed. Animal studies have demonstrated that tolazoline is concentrated in the liver and kidneys. Half life in horses at recommended doses is approximately 1 hour.
Contraindications/Precautions/Reproductive Safety - The manufacturer does not recommend use in horses exhibiting signs of stress, debilitation, cardiac disease, sympathetic blockage, hypovolemia or shock. Safe use for foals has not been established.
Tolazoline should be considered contraindicated in patients known to be hypersensitive to it, or who have coronary artery or cerebrovascular disease. Humans having any of the above contraindicative conditions, should use extra caution when handling the agent.
Safety during pregnancy, in breeding or lactating animals has not been established. It is unknown if the drug enters maternal milk.
Adverse Effects/Warnings - In horses adverse effects that may occur include: transient tachycardia; peripheral vasodilatation presenting as sweating and injected mucous membranes of the gingiva and conjunctiva; hyperalgesia of the lips (licking, flipping of lips); piloerection; clear lacrimal and nasal discharge; muscle fasciculations; apprehensiveness. Adverse effects should diminish with time and generally disappear within 2 hours of dosing. Potential for adverse effects increase if tolazoline is given at higher than recommended dosages or if xylazine has not been previously administered.
Overdosage - In horses given tolazoline alone (no previous xylazine), doses of 5X recommended resulted in gastrointestinal hypermotility with resultant flatulence and defecation or attempt to defecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction may be slowed when horses are overdosed, with a prolongation of the QRS-complex noted. Ventricular arrhythmias may occur resulting in death with higher overdoses (5X). In humans, ephedrine (NOT epinephrine or norepinephrine) has been recommended to treat serious tolazoline-induced hypotension.
Drug Interactions - If large doses of tolazoline are given with either norepinephrine or epinephrine, a paradoxical drop in blood pressure can occur followed by a precipitous increase in blood pressure. Accumulation of acetaldehyde can occur if tolazoline and alcohol are given simultaneously.
For reversal of xylazine effects:
a) 4 mg/kg slow IV (4 ml/220 lb. of body weight); administration rate should approximate 1 ml/second. (Package Insert; Tolazine®—Lloyd Laboratories)
a)To reverse juvenile wild African elephants immobilized with ketamine-xylazine, tolazoline 0.5 mg/kg IV will be effective in about 3 minutes (Raath, 1993).
b) To reverse xylazine give tolazoline at two times the xylazine dose (Kock, 1993).
c) As an antagonist to xylazine-ketamine .5 mg/kg IV (Allen, 1986).
a) Raath,J.P., 1993. Chemical capture of the African elephant. In: The Capture and care manual : capture, care, accommodation and transportation of wild African animals. Pretoria : Wildlife Decision Support Services : South African Veterinary Foundation, Pretoria pp. 484-511
b) Kock,R.A., Morkel,P., and Kock,M.D., 1993. Current immobilization procedures used in elephants. In: Fowler,M.E. (Editor), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA pp. 436-441
c) Allen,J.L. 1986. Use of tolazoline as an antagonist to xylazine-ketamine-induced immobilization in African elephants. American Journal of Veterinary Research 47:(4):781-783 Abstract: A group of 15 African elephants (Loxodonta africana) were immobilized with a combination of xylazine (0.2 mg/kg of body weight, IM) and ketamine (1 to 1.5 mg/kg of body weight, IM). Ten of the African elephants were allowed to remain recumbent for 30 minutes and the remaining 5 elephants, for 45 minutes before they were given tolazoline (0.5 mg/kg of body weight, IV). For the group of 15, the mean induction time (the time required from injection of the xylazine-ketamine combination until onset of recumbency) was 14.2 ± 4.35 minutes (mean ± SD), and standing time (the time required from the tolazoline injection until the elephant stood without stimulation or assistance) was 2.8 ± 0.68 minutes. All of the elephants were physically stimulated (by pushing, slapping, shouting) before they were given tolazoline, and none could be aroused. After tolazoline was given and the elephant was aroused, relapses to recumbency did not occur. Recovery was characterized by mild somnolence in an otherwise alert and responsive animal. Failure (no arousal) rates were 0% (95% confidence interval, 0 to 0.3085) for elephants given tolazoline after 30 minutes of recumbency and 100% for elephants that were not given tolazoline. There was no significant (P less than 0.05) difference in standing time 30 or 45 minutes after tolazoline injection.
Monitoring Parameters/Client Information- 1) Reversal effects (efficacy) 2) Adverse effects (see above). Because of the risks associated with the use of xylazine and reversal by tolazoline, these drugs should be administered and monitored by veterinary professionals only.
Dosage Forms/Preparations/FDA Approval Status -
Tolazoline HCl Injection 100 mg/ml in 100 ml multi-dose vials; Tolazine® (Lloyd); (Rx). Approved for use in horses; not to be used in food-producing animals.
Tolazoline HCl Injection 25 mg/ml; Priscoline®; HCl (Novartis); (Rx)
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