TOLAZOLINE HCL
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 slightaromatic odor. Tolazoline is freely soluble in ethanol or water. The commercially available (human)injection has pH between 3 and 4.
Tolazoline is rapid acting (usually within 5 minutes of IV administration), but has a short durationof action and repeat doses may be required.
Uses, Indications - Tolazoline is approved and indicated for the reversal of effects associated withxylazine in horses. It has also been used for this purpose in a variety of other species as well, butless safety and efficacy data is available.
In humans, the primary uses for tolazoline are: treatment of persistent pulmonary hypertension innewborns, adjunctive treatment and diagnosis of peripheral vasospastic disorders and as aprovocative test for glaucoma after subconjunctival injection.
Tolazoline should be considered contraindicated in patients known to be hypersensitive to it, orwho 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 unknownif the drug enters maternal milk.
Overdosage - In horses given tolazoline alone (no previous xylazine), doses of 5X recommendedresulted in gastrointestinal hypermotility with resultant flatulence and defecation or attempt todefecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction maybe slowed when horses are overdosed, with a prolongation of the QRS-complex noted. Ventriculararrhythmias may occur resulting in death with higher overdoses (5X). In humans, ephedrine (NOTepinephrine or norepinephrine) has been recommended to treat serious tolazoline-inducedhypotension.
Storage, Stability, Compatibility
Commercially available injection products should be storedbetween 15-30°C and protected from light. The drug is reportedly physically compatible with thecommonly used IV solutions.Pharmacology - TOLAZOLINE HCL
By directly relaxing vascular smooth muscle, tolazoline has peripheral vasodilating effects and decreases total peripheral resistance. Tolazoline also is a competitive alpha1 andalpha2 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 durationof action and repeat doses may be required.
Uses, Indications - Tolazoline is approved and indicated for the reversal of effects associated withxylazine in horses. It has also been used for this purpose in a variety of other species as well, butless safety and efficacy data is available.
In humans, the primary uses for tolazoline are: treatment of persistent pulmonary hypertension innewborns, adjunctive treatment and diagnosis of peripheral vasospastic disorders and as aprovocative test for glaucoma after subconjunctival injection.
Pharmacokinetics - TOLAZOLINE HCL
After IV injection in horses, tolazoline is widely distributed. Animal studieshave demonstrated that tolazoline is concentrated in the liver and kidneys. Half life in horses atrecommended doses is approximately 1 hour.Contraindications, Precautions, Reproductive Safety
The manufacturer does not recommenduse 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, orwho 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 unknownif 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 thegingiva and conjunctiva; hyperalgesia of the lips (licking, flipping of lips); piloerection; clearlacrimal and nasal discharge; muscle fasciculations; apprehensiveness. Adverse effects shoulddiminish with time and generally disappear within 2 hours of dosing. Potential for adverse effectsincrease if tolazoline is given at higher than recommended dosages or if xylazine has not be previously administered.Overdosage - In horses given tolazoline alone (no previous xylazine), doses of 5X recommendedresulted in gastrointestinal hypermotility with resultant flatulence and defecation or attempt todefecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction maybe slowed when horses are overdosed, with a prolongation of the QRS-complex noted. Ventriculararrhythmias may occur resulting in death with higher overdoses (5X). In humans, ephedrine (NOTepinephrine or norepinephrine) has been recommended to treat serious tolazoline-inducedhypotension.