틸레타민

The cardiopulmonary effects of three drug combinations in polar bears (Ursus maritimus) were studied. In 1995, five adult polar bears received im injections of either 8.2 +/- 1.3 mg/kg of Telazol or a combination of 159 +/- 34 ug/kg of medetomidine with 4 +/- 0.8 mg/kg of ketamine in a crossover design. Significantly higher mean arterial pressure, lower heart rate, and lower partial pressure of arterial oxygen (Pao2) occurred with medetomidine-ketamine. In 1996, six adult polar bears were immobilized with im injections of either 8.2 +/- 2 mg/kg of zolazepam-tiletamine or a combination of 74.8 +/- 11.8 ug/kg of medetomidine plus 2.2 +/- 0.3 mg/kg of zolazepam-tiletamine in a crossover design. Significantly higher mean arterial pressure and lower heart rate, base excess, and PaO2 occurred with medetomidine-zolazepam-tiletamine compared with zolazepam-tiletamine alone. Hypertension, bradycardia, and decreased PaO2 were observed with both medetomidine-ketamine and medetomidine-zolazepam-tiletamine. Both combinations should be well tolerated by healthy bears, but both have the potential to produce adverse effects in animals with cardiopulmonary disease. Zolazepam-tiletamine produced minimal adverse cardiopulmonary effects, consistent with the wide margin of safety of this combination in bears. The analgesic effect of zolazepam-tiletamine was apparently poor on the basis of the marked increases in pulse rate and mean arterial pressure after noxious stimuli.

Rats trained to discriminate between phencyclidine and saline vehicle were used to test various agents for their ability to mimic or block the phencyclidine cue. Ketamine, dexoxadrol, tiletamine, and phencyclidine analogs were found to mimic phencyclidine's behavioral effects. Treatment with the adenosine receptor agonists N6-cyclohexyladenosine and L-phenylisopropyladenosine blocked the discriminative properties of phencyclidine...

The cardiovascular and pulmonary effects of tiletamine/zolazepam, propofol and tiletamine/zolazepam plus propofol were studied in five mongrel dogs. A cannula inserted into a raised carotid artery was used to measure mean arterial pressure (MAP) and heart rate continuously and to collect arterial blood for the determination of pH, PO2, PCO2, bicarbonate and base balance. Respiratory frequency and rectal temperature were also recorded. In the two propofol groups premedication had no significant effect on the time to rejection of an endotracheal tube and the return to sternal recumbency. The MAP and heart rate increased after tiletamine/zolazepam alone and after tiletamine/zolazepam plus propofol, although propofol alone reduced MAP and transiently increased heart rate. Respiratory frequency decreased transiently in both propofol groups in association with a significant increase in PaCO2 and decrease in PaO2. The most notable change was the hypoxemia in the tiletamine/zolazepam plus propofol group in which the PaO2 was reduced. In all the dogs given tiletamine/zolazepam alone undesirable side effects were observed, effects which also occurred during the recovery of the dogs given tiletamine/zolazepam plus propofol.

The antinociceptive properties of tiletamine-zolazepam alone or combined with xylazine or butorphanol were determined in the adult male rat using the tail-flick test. Changes in tail-flick latency were determined at 15, 45, and 75 min after IP drug administration of sterile water, sodium pentobarbital, morphine, tiletamine-zolazepam, xylazine, butorphanol, and tiletamine-zolazepam plus xylazine or butorphanol. Tail-flick latency approximated 100% maximum possible effect (MPE) at 15-75 min postinjection in morphine-treated rats. Tiletamine-zolazepam, xylazine, and butorphanol alone, at any dose utilized, produced less than 50% MPE. However, the combination of tiletamine-zolazepam with butorphanol or xylazine increased tail-flick latency approximately three times greater than tiletamine-zolazepam alone. These results demonstrate that: a) consonant with earlier findings, analgesia and anesthesia are independent states; b) tiletamine-zolazepam is not an effective combination with respect to analgesia; but c) in concert with appropriate drugs, it can exhibit potent antinociceptive properties.

/SIGNS AND SYMPTOMS/ Potential organ systems affected are: Central Nervous System. Adverse effects could include: dizziness, light headedness, headache, nausea, and blurred vision. /Telazol/

/SIGNS AND SYMPTOMS/ Telazol causes almost immediate anesthetic effects, and sudden alertness is not uncommon as the effects of the drug subside. /Telazol/

/CASE REPORTS/ A 45-year-old male veterinarian was found dead in bed. Police investigation showed no evidence of trauma or other suspicious circumstances. Autopsy was unremarkable except for cardiomegaly and hepatosplenomegaly. Toxicological analysis revealed the presence of Telazol and ketamine. Telazol is a veterinary anesthetic agent that is composed of equal parts of tiletamine and zolazepam. Tiletamine is a disassociative anesthetic similar to ketamine and phencyclidine, and zolazepam is a diazepine derivative tranquilizer used to minimize the muscle hypertonicity and seizures associated with tiletamine. Quantitation of tiletamine and zolazepam was performed using gas chromatography-mass spectrometry in the selected ion monitoring mode following a solid-phase extraction. Postmortem blood, urine, and liver concentrations of tiletamine were 295 ng/mL, 682 ng/mL, and 196 ng/g, respectively, whereas postmortem concentrations of zolazepam for the same tissues were 1.71 ug/mL, 1.33 ug/mL, and 15.5 ug/g, respectively. Blood and urine ketamine levels were 37 ng/mL and 381 ng/mL, respectively. The cause of death was ruled an acute mixed drug intoxication of tiletamine, zolazepam, and ketamine with the manner of death ruled as unclassified.

/CASE REPORTS/ A 22-year-old male with more than 28 needle marks on his right arm was found dead. First, he was suspected as a drug abuser. Blood, urine, spleen, and injection-site tissue was collected during autopsy. The blood and urine specimens were screened for drugs. Immunoassay studies did not show any illegal drugs. However, two unidentified peaks were isolated in both of these biological fluids by routine gas chromatography-flame-ionization detection (GC-FID) and thermionic specific detection. Additional gas chromatography-mass spectrometry analysis determined these two peaks to be tiletamine and zolazepam. These two agents are used in combination as veterinary anesthesia. The concentrations of these drugs in blood were quantitated by GC-FID and found to be 0.85 mg/L of tiletamine and 3.3 mg/L of zolazepam. In urine, tiletamine and its metabolite, 2-(ethylamino)-2-(2-thionyl) cyclohexanol, were identified to be present along with zolazepam. The concentrations of tiletamine and zolazepam in spleen were revealed to be 0.92 and 3.5 mg/kg, respectively. Injection-site tissue concentrations were determined to be 25.1 mg/kg tiletamine and 23.3 mg/kg for zolazepam. The cause of death in this case was determined to be due to the multiple drug intoxication of tiletamine and zolazepam.

/CASE REPORTS/ A 30-year-old female employee at a local zoo was found unresponsive by fellow workers in a clean animal treatment room. Initial reports were that she had injected veterinary-grade diazepam and telazol. On-scene paramedics reported her as obtunded and arousable to deep painful stimuli, with gag reflex intact. Systolic blood pressure was 90 mm Hg by palpation. A fresh needle puncture mark was present on her right arm; nearby were a syringe, tourniquet, and bottles of each drug. Emergency Department assessment included airway, breathing, circulation, and intravenous access. She was lavaged and given activated charcoal with a cathartic. Shortly after arrival, she became alert and oriented. Family members insisted this was not an overdose. The patient had been previously evaluated for reported episodes of syncope, "only in the evening, while at work," and was prescribed diazepam for anxiety. Product information on telazol was limited to the Veterinary Drug Physician's Desk Reference. A urine drugs-of-abuse screen was positive for benzodiazepines and cannabinoids. The patient subsequently revealed a history of recreational use of telazol. She was discharged to an in-patient detoxification facility, 12 hours postadmission. /Telazol/

/LABORATORY ANIMALS: Acute Exposure/ To determine cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine (TZKD) combination in horses...8 healthy adult horses .../were/ given xylazine (0.44 mg/kg of body weight, IV) 10 to 15 minutes prior to induction of recumbency by administration of the TZKD combination. Cardiorespiratory, acid-base, and electrolyte values were measured at 5-minute intervals for >/= 30 minutes. ...All horses became recumbent within 1 minute after IV administration of TZKD. Mean +/- SD duration of recumbency was 40+/-8 minutes. All horses regained standing position after </= 2 attempts.... Xylazine induced decreases in respiratory rate, heart rate, cardiac output, maximum rate of increase of right ventricular pressure, and rate pressure product. The PaCO2, right atrial pressure, and peripheral vascular resistance increased, whereas blood temperature, PO2, pHa, HCO3-, PCV, total solids, Na, and K values remained unchanged. Subsequent administration of TZKD caused right atrial pressure and PaCO2 to increase and PaO2 to decrease, compared with values obtained after xylazine administration. Remaining cardiorespiratory, acid-base, hematologic, and electrolyte values did not differ from those obtained after xylazine administration.

/LABORATORY ANIMALS: Acute Exposure/ Telazol was evaluated as an anesthetic for rabbits. Two groups of five rabbits each were injected intramuscularly with 32 or 64 mg/kg of Telazol, and the depth and duration of anesthesia period monitored. At both doses, the righting reflex was lost within 2 minutes postinjection. Animals in both groups responded to noxious stimuli for the duration of the anesthesia. Hematology and urinalyses were performed daily for 7 days postinjection. Hematologic parameters remained unchanged in both groups. In the high-dose group, blood urea nitrogen and serum creatinine levels increased 1 day postinjection and continued steadily throughout the week. Elevations in urine protein and the presence of casts correlated with this increase. In the low-dose group, blood urea nitrogen and creatinine levels increased and protein was present in the urine of four of five rabbits beginning approximately 5 days postinjection. Histologically, severe renal tubular necrosis was evident 7 days postinjection in all high-dose rabbits and in three rabbits in the low-dose group. ... Telazol does not produce analgesia in rabbits and is nephrotoxic at both 32 and 64 mg/kg. ... Telazol is contraindicated for use in rabbits. /Telazol/

/LABORATORY ANIMALS: Neurotoxicity/ Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Tiletamine hydrochloride and zolazepam hydrochloride for injection. ... Indications for use. It is used for restraint or for anesthesia combined with muscle relaxation in cats and in dogs for restraint and minor procedures of short duration (30 minutes) requiring mild to moderate analgesia. ... Limitations. Discard unused reconstituted solution after 48 hours. Not for use in dogs and cats with pancreatic disease, or with severe cardiac or pulmonary dysfunction. Not for use in pregnant animals. Not for use in cats suffering with renal insufficiency. The dosage should be reduced in geriatric dogs and cats. Federal law restricts this drug to use by or on the order of a licensed veterinarian. /Tiletamine hydrochloride and zolazepam hydrochloride/

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a depressant effect on the central nervous system: Tiletamine and zolazepam or any salt thereof. DEA Code Number: 7295.

/VET/ Telazol (tiletamine hydrochloride 50 mg/mL, zolazepam hydrochloride 50 mg/mL) is utilized in veterinary medicine as a ... anesthetic.

... marketed as /tiletamine/ hydrochloride salt in combination with zolazepam hydrochloride as Telazol solution for intramuscular administration to dogs and cats