Product name: Tiletamine Hydrochloride
Synonyms:Cyclohexanone, 2-(ethylamino)-2-(2-thienyl)-, hydrochloride;
Tiletamine Hydrochloride;CI-634;CL-399;CN-54521-2;Nsc167740;Tiletamin hydrochloride
CAS:14176-50-2
MF: C12H17NOS.ClH
MW:259.799
Chemical Properties:White to off-white solid
Usage:Tiletamine is a receptor antagonist, an anesthetic.
Tiletamine-Zolazepam (tiletamine HCl and zolazepam HCl) is a nonnarcotic, nonbarbiturate, injectable anesthetic agent for dogs and cats. Chemically, Tiletamine-Zolazepam is a combination of equal parts by weight of base of tiletamine hydrochloride (2-[ethylamino]-2- [2-thienyl]- cyclohexanone hydrochloride), an arylaminocycloalkanone dissociative anesthetic, and zolazepam hydrochloride (4-[o-fluorophenyl]-6,8-dihydro-1,3,8- trimethylpyrazolo [3, 4-e] [1,4] diazepin-7[1H]- 1-hydrochloride), a non-phenothiazine diazepinone having minor tranquilizing properties. The product is supplied sterile in vials. The addition of 5 mL diluent produces a solution containing the equivalent of 50 mg tiletamine base, 50 mg zolazepam base and 57.7 mg mannitol per milliliter. This solution has a pH of 2 to 3.5 and is recommended for deep intramuscular injection.
ACTIONS: Tiletamine-Zolazepam is a rapid-acting anesthetic combination of tiletamine hydrochloride and zolazepam hydrochloride. Tiletamine hydrochloride is a dissociative anesthetic agent whose pharmacologic action is characterized by profound analgesia, normal pharyngeal-laryngeal reflexes and cataleptoid anesthesia. The anesthetic state produced does not fit into the conventional classification of stages of anesthesia, but instead Tiletamine-Zolazepam produces a state of unconsciousness which has been termed “dissociative” anesthesia in that it appears to selectively interrupt association pathways to the brain before producing somesthetic sensory blockade.
Cranial nerve and spinal reflexes remain active; however, these reflexes must not be confused with inadequate anesthesia. Analgesia results from apparent selective interruption of sensory inputs to the brain and usually persists after the anesthetic effect has subsided.
Protective reflexes, such as coughing and swallowing, are maintained under tiletamine anesthesia. Other reflexes, e.g., corneal, pedal, are maintained during tiletamine anesthesia, and should not be used as criteria for judging depth of anesthesia. The eyes normally remain open with the pupil dilated. It is suggested that a bland ophthalmic ointment be applied to the cornea if anesthesia is to be prolonged.
Used alone, tiletamine hydrochloride does not provide adequate muscle relaxation for abdominal surgical procedures. When combined with zolazepam hydrochloride, good muscle relaxation is generally attained during the phase of deep surgical anesthesia.
Following a single, deep intramuscular injection of Tiletamine-Zolazepam in cats and dogs, onset of anesthetic effect usually occurs within 5 to 12 minutes. Muscle relaxation is optimum for approximately the first 20 to 25 minutes after Tiletamine-Zolazepam is administered, and then diminishes. Recovery varies with the age and physical condition of the animal and the dose of Tiletamine-Zolazepam administered, but usually requires several hours. Recovery is extended with multiple injections, particularly in cats.
Repeated doses increase the duration of the effect of Tiletamine-Zolazepam but may not further diminish muscle tone. The quality of anesthesia with repeated doses varies because the ratio of the two components within the animal’s body changes with each injection. This is due to the difference in the rates of metabolism and elimination of the two components. The quality of anesthesia will be improved and more predictable if the entire dose is given as a single injection rather than in several doses. The best method of evaluating the depth of Tiletamine-Zolazepam anesthesia is to monitor the patient for deliberate conscious response to nociceptive stimuli.
Copious salivation may occur during Tiletamine-Zolazepam anesthesia. Ptyalism may be controlled in dogs and cats by giving atropine sulfate, USP, 0.02 mg/lb (0.04 mg/kg) body weight, as concurrent medication. Exaggerated swallowing, reflex action and accumulation of saliva may give rise to vomiting and retching.
Tiletamine-Zolazepam has a wider margin of safety in cats than in dogs. Dogs have survived repeated dosage regimens of 13.6 mg/lb (30 mg/kg) (maximum safe dose) for eight successive days. This is approximately two times the maximum recommended therapeutic dose. Cats have survived dosage regimens of up to 32.7 mg/lb (72 mg/kg) (maximum safe dose) on alternate days for seven episodes. This is 4.6 times the maximum recommended therapeutic dose for cats. However, these reports should not obviate prudent anesthetic practices. Some degree of tolerance has been reported. This tolerance appears to be species-variable.
Cats: In cats, the duration of effect of zolazepam exceeds that of tiletamine so that as the animal recovers there is a greater degree of tranquilization than anesthetization. There is a slight lowering of blood pressure during the first hour after injection. Heart rate and electrocardiogram readings are unaffected by Tiletamine-Zolazepam (tiletamine HCI and zolazepam HCI). Arterial pO2 levels are decreased three minutes after injection but usually return to normal within 15 to 35 minutes.
Dogs: In dogs, the duration of effect of tiletamine exceeds that of zolazepam so there is a lesser degree of tranquilization than anesthetization in this species. The total effect of Tiletamine-Zolazepam in dogs is of shorter duration than in cats.
Following administration of Tiletamine-Zolazepam in dogs, a marked, persistent tachycardia occurs within two minutes following either 4.5 or 9 mg/lb (10 or 20 mg/kg) Tiletamine-Zolazepam intramuscularly. Stroke volume decreases proportionately to the increased rate at the 4.5 mg/lb (10 mg/kg) dose, with little change in net cardiac output. There is an initial increase in systolic blood pressure, with a slight drop in pressure within five minutes. The systolic blood pressure remains at this decreased level throughout the duration of the anesthetic effect. Diastolic pressure increases throughout this same period. Following a 9 mg/lb (20 mg/kg) dose of Tiletamine-Zolazepam in dogs, the relationship between stroke volume and heart rate is disproportionate, with a resultant substantial decrease in cardiac output. Contractility and mean blood pressure are decreased, indicating direct myocardial depression. Ventricular function is adequate. During surgical manipulations, tachycardia and hypertension may be observed, and may be brought on by sympathetic reaction to painful stimuli. Epinephrine is markedly less arrhythmogenic in animals under Tiletamine-Zolazepam anesthesia than in those under halothane anesthesia.
During Tiletamine-Zolazepam anesthesia, the assurance of a patent airway is greatly enhanced by virtue of maintaining pharyngeal-laryngeal reflexes. During the first 15 minutes after intramuscular administration of 9 mg/lb (20 mg/kg) of Tiletamine-Zolazepam, the respiratory rate is doubled while the tidal volume is decreased to less than one-half of control values. Arterial pO2 levels also decrease. This may be evidenced by hypoxemia and cyanosis. The pulmonary function usually returns to normal within 35 minutes after the administration of Tiletamine-Zolazepam.
Tiletamine-Zolazepam Indications
Tiletamine-Zolazepam is indicated in cats for restraint or for anesthesia combined with muscle relaxation and in dogs for restraint and minor procedures of short duration (30 min. avg.) requiring mild to moderate analgesia. Minor surgery is considered to be laceration repair, draining of abscesses, castrations and other procedures requiring mild to moderate analgesia. (See Dogs under ADMINISTRATION AND DOSAGE)
Contraindications
The use of Tiletamine-Zolazepam is contraindicated in dogs and cats with pancreatic disease. Tiletamine-Zolazepam is excreted predominately by the kidneys. Preexistent renal pathology or impairment of renal function may be expected to result in prolonged duration of anesthesia. Tiletamine-Zolazepam should not be used in dogs and cats with severe cardiac or pulmonary dysfunction. Because the teratogenic potential of Tiletamine-Zolazepam is unknown, it should not be used in pregnant bitches or queens at any stage of pregnancy. Also, a study has shown that tiletamine HCI and zolazepam HCI crosses the placental barrier and produces respiratory depression in the newborn; therefore, its use for Cesarean section is contraindicated.
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