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1.
J Wildl Dis ; 54(2): 362-365, 2018 04.
Article in English | MEDLINE | ID: mdl-29148888

ABSTRACT

Previous studies demonstrated that nalbuphine, medetomidine, and azaperone (NalMed-A) can effectively immobilize adult elk ( Cervus elaphus nelsoni), and be antagonized using naltrexone and atipamezole, with or without tolazoline. To assess duration of tissue residues for this immobilization package, we immobilized 14 captive adult elk with NalMed-A, then euthanized animals and collected tissues 0, 3, 6, 14, 21, or 28 d later. Except for two animals euthanized immediately, all elk were recovered using naltrexone, atipamezole, and tolazoline. Tissue residues (≥0.01 parts per million) for the tranquilizers nalbuphine, medetomidine, and azaperone were detected in liver and muscle tissue samples from elk euthanized within 40 min postinjection (PI) and one animal that died 12-24 h PI, but not in tissues from any of the animals euthanized at 3, 6, 14, 21, or 28 d PI. Tissue residues for the antagonists naltrexone, atipamezole, and tolazoline were detected in liver and muscle of the animal that died 12-24 h PI. Only naltrexone was detected in liver from the two elk euthanized at day 3, and no antagonist residues were detected thereafter.


Subject(s)
Deer , Drug Residues , Hypnotics and Sedatives/pharmacokinetics , Narcotic Antagonists/pharmacokinetics , Narcotics/pharmacokinetics , Animals , Azaperone/administration & dosage , Azaperone/pharmacokinetics , Azaperone/pharmacology , Drug Combinations , Female , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Imidazoles/administration & dosage , Imidazoles/pharmacokinetics , Imidazoles/pharmacology , Immobilization , Medetomidine/administration & dosage , Medetomidine/pharmacokinetics , Medetomidine/pharmacology , Nalbuphine/administration & dosage , Nalbuphine/pharmacokinetics , Nalbuphine/pharmacology , Naltrexone/administration & dosage , Naltrexone/pharmacokinetics , Narcotic Antagonists/administration & dosage , Narcotic Antagonists/pharmacology , Narcotics/administration & dosage , Narcotics/pharmacology , Tolazoline/administration & dosage , Tolazoline/pharmacokinetics , Tolazoline/pharmacology
2.
J Wildl Dis ; 50(3): 676-80, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24807358

ABSTRACT

We compared dosages of a combination of sedatives, which included butorphanol tartrate, azaperone tartrate, and medetomidine HCl (BAM) in captive adult Rocky Mountain elk (Cervus elaphus nelsoni). All three BAM dosages (low, medium, and high) effectively immobilized elk and produced an adequate level of sedation in all subjects. Induction times were similar among the three groups (mean ± SD: low=6.9 ± 1.1 min; medium=6.3 ± 0.9 min; high=4.7 ± 1.3 min). Most elk became hypoxemic regardless of BAM dosage, but hypoxemia tended to be most severe in the high-BAM group; regardless of BAM dosage, oxygen supplementation improved the percentage of oxygen saturation and stabilized the vital rates. Recovery after administration of antagonists (3 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline) was comparable among groups (range of means=9 ± 1.5-11.7 ± 1 min). Based on the findings from clinical trials and field data from free-ranging elk immobilizations, we recommend low-dose BAM (2 mL dose; equivalent to 46 mg butorphanol, 30 mg azaperone, and 18 mg medetomidine) and supplemental oxygen for adult elk; immobilization should be antagonized using 3-5 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline, with tolazoline injected about 5-10 min before atipamezole to smooth out recovery.


Subject(s)
Azaperone/pharmacology , Butorphanol/pharmacology , Deer/physiology , Immobilization/veterinary , Medetomidine/pharmacology , Adrenergic alpha-2 Receptor Antagonists/administration & dosage , Adrenergic alpha-2 Receptor Antagonists/pharmacology , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/pharmacology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Animals , Azaperone/administration & dosage , Butorphanol/administration & dosage , Dose-Response Relationship, Drug , Drug Combinations , Female , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Imidazoles/administration & dosage , Imidazoles/pharmacology , Immobilization/methods , Male , Medetomidine/administration & dosage , Tolazoline/administration & dosage , Tolazoline/pharmacology
3.
Vet Anaesth Analg ; 41(1): 36-47, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24134603

ABSTRACT

OBJECTIVE: To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. STUDY DESIGN: Randomized crossover design. ANIMALS: Nine healthy adult horses with an average age of 7.6 ± 6.5 years. METHODS: Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. RESULTS: Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. CONCLUSIONS AND CLINICAL RELEVANCE: At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.


Subject(s)
Horses/blood , Imidazoles/pharmacology , Imidazoles/pharmacokinetics , Tolazoline/pharmacology , Yohimbine/pharmacology , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/blood , Adrenergic alpha-Antagonists/pharmacokinetics , Adrenergic alpha-Antagonists/pharmacology , Animals , Cross-Over Studies , Drug Interactions , Female , Imidazoles/administration & dosage , Imidazoles/blood , Male , Tolazoline/administration & dosage , Tolazoline/blood , Tolazoline/pharmacokinetics , Yohimbine/administration & dosage , Yohimbine/blood , Yohimbine/pharmacokinetics
4.
J Pharm Sci ; 102(11): 4072-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23996466

ABSTRACT

The purpose of the study was to evaluate the effect of adding peripheral vasodilators, tolazoline, or papaverine, to transdermal drug delivery vehicles with the goal of improving the tissue bioavailability of transdermally delivered ibuprofen. Ibuprofen (150 mg) formulations with several concentrations of two different vasodilators and/or a penetration enhancer (PE) complex were topically applied to rabbits. Plasma levels of ibuprofen were determined by a validated high-performance liquid chromatography method and evaluated at 0, 0.5, 1, 2, and 3 h. The PE complex enhanced the plasma ibuprofen level approximately sevenfold versus control, and tolazoline (0.005%) added to the PE complex increased the plasma levels of ibuprofen approximately another twofold compared with the PE. Higher concentrations of tolazoline paradoxically did not exhibit vasodilator enhancement to ibuprofen delivery. Papaverine was tested in the same manner. In this set of experiments, PE increased the plasma ibuprofen 3.7-fold versus control, and addition of papaverine (0.0005%) increased plasma ibuprofen an additional 3.3-fold compared with the PE formulation. Transdermal formulations of ibuprofen containing low concentrations of tolazoline or papaverine increased plasma ibuprofen levels in the presence of passive PE components.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ibuprofen/administration & dosage , Papaverine/pharmacology , Skin Absorption/drug effects , Tolazoline/pharmacology , Vasodilator Agents/pharmacology , Administration, Cutaneous , Animals , Anti-Inflammatory Agents, Non-Steroidal/blood , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Ibuprofen/blood , Ibuprofen/pharmacokinetics , Permeability/drug effects , Rabbits , Skin/drug effects , Skin/metabolism , Tolazoline/administration & dosage , Vasodilator Agents/administration & dosage
5.
Vet J ; 196(3): 504-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23321455

ABSTRACT

Tolazoline is an α2-adrenergic receptor antagonist, used in veterinary medicine to antagonize the central nervous system depressant and cardiovascular effects of α2 receptor agonists. The pharmacokinetics and pharmacodynamic effects of tolazoline when administered subsequent to detomidine in the horse were recently reported, although the reversal of the sedative and cardiovascular effects following detomidine may not be complete. The current study therefore investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses were administered tolazoline (4mg/kgIV) and blood samples were collected at time 0 (prior to drug administration) and at various times up to 72h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and resulting data analyzed using compartmental analysis. Systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820±0.182L/h/kg, 1.68±0.379L/kg and 2.69±0.212h, respectively. Tolazoline administration had no effect on chin to ground distance, but the heart rate decreased (relative to baseline) and the percentage of atrial-ventricular block increased in all horses within 2min of administration. Packed cell volume and glucose concentrations were also increased throughout the sampling period. While not commonly used as a sole agent, caution is indicated whenever tolazoline is administered since the effects may be unpredictable.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Adrenergic alpha-Antagonists/pharmacokinetics , Horses/blood , Tolazoline/pharmacology , Tolazoline/pharmacokinetics , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/blood , Animals , Area Under Curve , Blood Proteins , Female , Half-Life , Heart Rate , Injections, Intravenous , Male , Tolazoline/administration & dosage , Tolazoline/blood
6.
J Wildl Dis ; 48(4): 1088-91, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23060515

ABSTRACT

Free-ranging Alaskan moose calves (Alces alces gigas) were immobilized with 0.12 mg/kg sufentanil (S; n=16), 0.12 mg/kg sufentanil plus 0.27 mg/kg xylazine (SX; n=11), or 0.007 mg/kg carfentanil plus 0.36 mg/kg xylazine (CX; n=13). Immobilants were antagonized with 1.2 mg/kg naltrexone (S) or 1.2 mg/kg naltrexone plus 2.4 mg/kg tolazoline (SX, CX). There were no differences in induction (P ≥ 0.29) or processing (P ≥ 0.44) times between groups. Moose given either S or SX had significantly shorter recovery times than moose given CX (P=0.001) and recovery times from S were shorter than from SX (P=0.02). Oxygen saturation values for all groups averaged 85 ± 8%, but were significantly higher (P=0.048) for CX (89 ± 7%) than for S (82 ± 8%). Based on these data, sufentanil at 0.1 mg/kg or sufentanil at 0.1 mg/kg plus xylazine at 0.25 mg/kg could provide effective remote immobilization for Alaskan moose calves and could be substituted for carfentanil or thiafentanil should the need arise.


Subject(s)
Deer/physiology , Immobilization/veterinary , Narcotics/pharmacology , Sufentanil/pharmacology , Alaska , Anesthesia Recovery Period , Animals , Animals, Newborn , Animals, Wild , Dose-Response Relationship, Drug , Female , Fentanyl/analogs & derivatives , Fentanyl/pharmacology , Immobilization/methods , Male , Naltrexone/administration & dosage , Oxygen/blood , Respiration/drug effects , Time Factors , Tolazoline/administration & dosage , Xylazine/pharmacology
7.
J Zoo Wildl Med ; 42(1): 105-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-22946377

ABSTRACT

Eighteen mule deer (Odocoileus hemionus) and six Columbia black-tailed deer (Odocoileus hemionus columbianus) were held in pens and repeatedly anesthetized from April 2004 through June 2005 as part of an external parasite study. Deer were anesthetized using a combination of Telazol and xylazine hydrochloride (HCL) administered intramuscularly. Tolazoline HCL was slowly administered at 4 mg/kg intravenously to reverse the effects of xylazine with good results. For 17 of the 19 mule deer anesthesias in the fall of 2004, a mean dose of 7.3 mg/kg of intravenous tolazoline (range 6.1-8.4 mg/kg) was given by mistake. This paper describes clinical signs of apnea, muscle tensing, and fasciculations immediately following intravenous administration of tolazoline HCL in mule deer (O. hemionus) at 1.5-3 times the recommended dose. Mean dose for black-tailed deer during this time was 8.1 mg/kg (range 5.5-12.4 mg/kg) with no clinical signs as seen in the mule deer. Based on these findings, intravenous tolazoline use in mule deer is recommended at < or = 4 mg/kg.


Subject(s)
Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/adverse effects , Apnea/veterinary , Deer , Tolazoline/administration & dosage , Tolazoline/adverse effects , Anesthetics/pharmacology , Animals , Apnea/chemically induced , Dose-Response Relationship, Drug , Drug Overdose/veterinary , Fasciculation/chemically induced , Fasciculation/veterinary
8.
Catheter Cardiovasc Interv ; 73(2): 152-5, 2009 Feb 01.
Article in English | MEDLINE | ID: mdl-19156878

ABSTRACT

Nonocclusive mesenteric ischemia (NOMI) generally affects patients with low cardiac output, resulting in splanchnic hypoperfusion. It includes all forms of mesenteric ischemia without vessel occlusion and makes up between 20 and 30% of all cases of acute mesenteric ischemia. We present the case of a 84-year-old man with a history of total atrioventricular block developing NOMI. This was diagnosed by percutaneous selective catheter arteriography (PSCA), which demonstrated remarkable abrupt termination of the jejunal vasculature and multiple severe spasms of the colonic arteries. Control PSCA after local intraarterial vasodilator therapy (LIVT) with tolazoline and glycerol trinitrate documented an excellent therapeutic result with a completely unremarkable vasculature. Although LIVT was complicated by severe cardiovascular complications inclusive of cardiac arrest with the need of cardiopulmonary resuscitation, the patient fully recovered and was discharged after implantation of a cardiac pacemaker in good clinical condition 7 days later.


Subject(s)
Colon/blood supply , Ischemia/drug therapy , Jejunum/blood supply , Nitroglycerin/administration & dosage , Tolazoline/administration & dosage , Vasodilator Agents/administration & dosage , Aged, 80 and over , Cardiopulmonary Resuscitation , Drug Therapy, Combination , Heart Diseases/complications , Heart Diseases/therapy , Humans , Infusions, Intravenous , Injections, Intra-Arterial , Ischemia/complications , Ischemia/diagnostic imaging , Male , Pacemaker, Artificial , Radiography , Treatment Outcome
9.
Vet Anaesth Analg ; 31(2): 90-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15053746

ABSTRACT

OBJECTIVE: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular xylazine/ketamine in llamas, and to determine if an intramuscular injection of tolazoline would shorten the anesthesia recovery time. STUDY DESIGN: Prospective randomized study. ANIMALS: Six castrated male llamas. METHODS: Each llama received a low dose (LD) (0.4 mg kg(-1) xylazine and 4 mg kg(-1) ketamine) and high dose (HD) (0.8 mg kg(-1) xylazine and 8 mg kg(-1) ketamine). Time to sedation, duration of lateral recumbency and analgesia, pulse, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood gases, and the electrocardiogram were monitored and recorded during anesthesia. Three llamas in each treatment were randomized to receive intramuscular tolazoline (2 mg kg(-1)) after 30 minutes of lateral recumbency. RESULTS: Onset of sedation, lateral recumbency, and analgesia was rapid with both treatments. The HD was able to provide at least 30 minutes of anesthesia in all six llamas. The LD provided only 30 minutes of anesthesia in two out of six llamas. Respiratory depression and hypoxemia were seen in the HD treatment during the first 10 minutes of lateral recumbency. Two llamas were severely hypoxemic during this period and were given nasal oxygen for five minutes. Heart rate decreased, but there were no significant changes in blood pressure. Tolazoline significantly shortened the duration of recumbency in the HD treatment. CONCLUSIONS: The HD provided more consistent clinical effects in llamas than did the LD. Intramuscular tolazoline shortens the duration of lateral recumbency in llamas anesthetized with this combination. CLINICAL RELEVANCE: Both doses appear to be very effective in providing restraint in llamas. The LD may be used for procedures requiring a short period of anesthesia or restraint. The HD could be used when a longer duration of anesthesia is desired. Supplemental oxygen should be available if using the HD. Tolazoline (IM) shortened the recovery time with this combination in llamas.


Subject(s)
Anesthesia, General/veterinary , Camelids, New World/physiology , Ketamine/pharmacology , Tolazoline/pharmacology , Xylazine/pharmacology , Animals , Blood Gas Analysis/veterinary , Drug Combinations , Electrocardiography/drug effects , Injections, Intramuscular/veterinary , Ketamine/administration & dosage , Male , Prospective Studies , Pulse , Respiration/drug effects , Tolazoline/administration & dosage , Xylazine/administration & dosage
10.
Vet Ther ; 4(2): 128-34, 2003.
Article in English | MEDLINE | ID: mdl-14506588

ABSTRACT

Xylazine hydrochloride was administered i.m. at 0.35 mg/kg to 13 steers and 10 lactating dairy cows at Time 0. Ten minutes later, tolazoline hydrochloride was given i.v. at 4 mg/kg. Tissue and milk samples were analyzed using gas chromatography with nitrogen and phosphorous detection to determine concentrations of xylazine, 2,6-dimethylaniline (a toxic metabolite of xylazine), and tolazoline (at various intervals). Concentrations of xylazine and 2,6- dimethylaniline were below the limit of quantitation (10 microg/kg) by 72 hours in tissues and 12 hours in milk. The concentration of tolazoline was below 10 microg/kg by 96 hours in tissues and 48 hours in milk. Based on the results of these residue studies submitted by the sponsoring agency to the Ministry of Agriculture and Forestry in New Zealand, withholding periods for both xylazine hydrochloride and tolazoline hydrochloride injection were established.


Subject(s)
Adrenergic alpha-Agonists/pharmacokinetics , Adrenergic alpha-Antagonists/pharmacokinetics , Aniline Compounds/pharmacokinetics , Cattle/metabolism , Milk/metabolism , Tolazoline/pharmacokinetics , Xylazine/pharmacokinetics , Adrenergic alpha-Agonists/administration & dosage , Adrenergic alpha-Agonists/blood , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/blood , Aniline Compounds/blood , Animals , Dairying , Drug Residues/metabolism , Female , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/antagonists & inhibitors , Infusions, Intravenous/veterinary , Injections, Intramuscular/veterinary , Kidney/metabolism , Liver/metabolism , Muscle, Skeletal/metabolism , Random Allocation , Tolazoline/administration & dosage , Tolazoline/blood , Xylazine/administration & dosage , Xylazine/blood
12.
Pediatrics ; 109(5): 852-6, 2002 May.
Article in English | MEDLINE | ID: mdl-11986446

ABSTRACT

OBJECTIVE: To determine the efficacy of tolazoline as a rescue treatment for hypoxemia in preterm infants with respiratory distress syndrome. METHODS: Retrospective chart review on case series of infants weighing < 750 g at birth who received tolazoline during a severe hypoxemic episode while receiving maximal ventilator support for respiratory distress syndrome. A slow bolus infusion of low dose tolazoline (0.5 mg-2 mg/kg) mixed with plasmanate or normal saline (10 mL/kg) was administered. Outcome measures evaluated included an increase in PaO(2) > or =20 mm Hg from pretreatment value and an increase in oxygen saturation to > or =90%. RESULTS: Forty-three infants with a mean gestational age and birth weight of 24 weeks and 581 g, respectively, received tolazoline. All infants were mechanically ventilated and required a fraction of inspired oxygen of 1.0. Oxygenation improved in 72% (31/43) of infants with a tolazoline dose of 0.5 to 1.0 mg/kg. Of those who responded, PaO(2) values (mean +/- standard deviation) pretolazoline and posttolazoline were 32 +/- 7.5 mm Hg and 156 +/- 114.9 mm Hg, respectively. In all responders, oxygen saturation increased to > or =90% within 30 minutes of tolazoline administration. Improvement in pH, pCO(2), oxygenation index, and mean airway pressure was also noted. Among nonresponders, pH decreased and pCO(2) increased after tolazoline. Minimal change in blood pressure was noted in both responders and nonresponders. Heart rate decreased by 19 beats per minute among nonresponders compared with an increase of 3 beats per minute in those who responded to tolazoline. CONCLUSION: Tolazoline is an effective treatment of severe resistant hypoxemia in preterm infants who are already on vigorous ventilatory support.


Subject(s)
Hypoxia/drug therapy , Respiratory Distress Syndrome, Newborn/therapy , Tolazoline/therapeutic use , Vasodilator Agents/therapeutic use , Blood Pressure/drug effects , Blood Proteins/therapeutic use , Carbon Dioxide/blood , Carbon Dioxide/metabolism , Dose-Response Relationship, Drug , Female , Gestational Age , Heart Rate/drug effects , Humans , Hypertension, Pulmonary/drug therapy , Hypoxia/etiology , Hypoxia/metabolism , Infant, Newborn , Infant, Very Low Birth Weight , Infusions, Intravenous , Intensive Care Units, Neonatal , Leukomalacia, Periventricular/epidemiology , Oxygen/blood , Oxygen/metabolism , Pregnancy , Respiration, Artificial , Respiratory Distress Syndrome, Newborn/complications , Respiratory Distress Syndrome, Newborn/drug therapy , Serum Albumin , Serum Albumin, Human , Serum Globulins , Severity of Illness Index , Tolazoline/administration & dosage , Treatment Outcome , Vasodilator Agents/administration & dosage
13.
J Vasc Interv Radiol ; 12(11): 1273-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11698625

ABSTRACT

PURPOSE: The purpose of this study was to assess the efficacy and safety of provocative mesenteric angiography with tissue plasminogen activator (tPA), heparin, and tolazoline in patients with nonlocalized lower gastrointestinal (LGI) bleeding. Results were examined to assess the clinical impact of the study on patients who had positive or negative results from elective provocative bleeding studies. MATERIALS AND METHODS: Seventeen provocative bleeding studies for occult LGI bleeding were performed in 16 patients, nine of whom were women, aged 44-79 years. All patients had negative results from previous endoscopic and angiographic studies. Patients' requirements for blood transfusion ranged from 6 to 69 units. Studies were performed electively. Blood group matching and cross-matching were performed for all patients. To provoke bleeding, a combination of intravenous heparin, intraarterial tolazoline, and intraarterial tPA was used. Doses used included 3,000-10,000 U heparin, 25-100 mg intraarterial tolazoline, and 10-50 mg intraarterial tPA (mean, 20.3 mg). Duration of follow-up was 3-34 months. RESULTS: Seventeen elective provocative studies were performed in 16 patients with occult LGI bleeding, leading to provoked bleeding in six patients (37.5%). In addition, two previously undiagnosed vascular abnormalities were diagnosed, which did not bleed during provocation. Therefore, an abnormality was identified in eight of 16 patients (50%) overall. There were no procedural complications encountered during or after any of the 17 procedures. In six patients in whom bleeding was successfully provoked, four bleeding episodes occurred in the large bowel and two occurred in the small bowel. Five of the positively provoked patients had a previously positive tagged red cell scintigraphic study. Three patients had superselective embolization at the time of provoked bleeding. Two were treated with estrogen therapy, and one patient was treated palliatively. Five of these six patients required no further therapy for LGI bleeding. Ten patients (including two with vascular abnormalities) did not bleed during the provoked study with tPA. Follow-up of the group of eight patients with completely normal study results ranged from 3 to 34 months in duration, and during the follow-up period, five patients experienced repeated bleeding and one had no further bleeding. One patient was diagnosed with an ileal vascular lesion during subsequent intraoperative enteroscopy and underwent surgical resection. One patient was lost to follow-up. CONCLUSION: Intraarterial provocative mesenteric angiography with heparin, vasodilator, and tPA identified the site of bleeding in 37.5% of patients in our study group and contributed to treatment in 50%. This small study indicates that the procedure appears to be safe, with no complications encountered in this series. Larger prospective studies are needed to fully assess the safety and efficacy of the technique and to optimize the pharmacologic protocol and patient selection.


Subject(s)
Fibrinolytic Agents/administration & dosage , Gastrointestinal Hemorrhage/diagnostic imaging , Heparin/administration & dosage , Tissue Plasminogen Activator/administration & dosage , Tolazoline/administration & dosage , Vasodilator Agents/administration & dosage , Adult , Aged , Angiography , Female , Humans , Injections, Intra-Arterial , Injections, Intravenous , Male , Middle Aged , Retrospective Studies
14.
J Am Vet Med Assoc ; 216(2): 227-9, 194, 2000 Jan 15.
Article in English | MEDLINE | ID: mdl-10649759

ABSTRACT

Clinical signs of tolazoline toxicosis developed in a 4-year-old llama that received 2 doses of tolazoline hydrochloride to reverse xylazine-induced sedation. The full first dose (4.3 mg/kg [2.0 mg/lb] of body weight) was erroneously injected i.v., and the second dose was administered half i.v., half i.m. 45 minutes later, because the llama became weak and recumbent. Signs of anxiety, hyperesthesia, profuse salivation, and tachypnea were the first detectable clinical signs of tolazoline toxicosis. Convulsions, hypotension, gastrointestinal tract hypermotility, and diarrhea also developed. The llama was treated successfully with i.v. administration of diazepam, phenylephrine, and lactated Ringer's solution supplemented with potassium chloride and oxygen administered via nasal insufflation. We suggest that the maximum dose of tolazoline administered at any one time to llamas not exceed 2 mg/kg (0.91 mg/lb). Furthermore, tolazoline should be administered slowly i.v. or i.m. to reduce the risk of adverse reactions.


Subject(s)
Adrenergic alpha-Antagonists/adverse effects , Camelids, New World/physiology , Tolazoline/adverse effects , Adrenergic alpha-Agonists , Adrenergic alpha-Antagonists/administration & dosage , Animals , Anticonvulsants/therapeutic use , Diazepam/therapeutic use , Edema/chemically induced , Edema/therapy , Edema/veterinary , Female , Fluid Therapy/veterinary , Hypnotics and Sedatives/antagonists & inhibitors , Injections, Intramuscular/veterinary , Injections, Intravenous/adverse effects , Injections, Intravenous/veterinary , Nasal Decongestants/therapeutic use , Nose Diseases/chemically induced , Nose Diseases/therapy , Nose Diseases/veterinary , Oxygen Inhalation Therapy , Phenylephrine/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Seizures/veterinary , Tolazoline/administration & dosage , Tracheotomy/veterinary , Xylazine/antagonists & inhibitors
15.
Acta Paediatr ; 88(9): 1020-3, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10519347

ABSTRACT

Tolazoline is a potent vasodilator of both arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36; 13.16) microg/ml. The extent of tolazoline absorption was 305 (148;453) microg/ min/ml. The volume of distribution was 3.4 (1.6;7.4) 1/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.


Subject(s)
Hemodynamics/drug effects , Tolazoline/pharmacology , Tolazoline/pharmacokinetics , Vasodilator Agents/pharmacology , Vasodilator Agents/pharmacokinetics , Animals , Animals, Newborn , Area Under Curve , Dogs , Female , Gas Chromatography-Mass Spectrometry , Intubation, Intratracheal , Male , Tolazoline/administration & dosage , Tolazoline/blood , Vasodilator Agents/administration & dosage , Vasodilator Agents/blood
16.
Am J Perinatol ; 16(1): 1-6, 1999.
Article in English | MEDLINE | ID: mdl-10362074

ABSTRACT

Tolazoline is a potent vasodilator of arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in the systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endobronchial tolazoline to determine the relationship between endobronchial tolazoline administration, plasma concentration, and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endobronchially to seven dogs, and its serum concentration and the hemodynamic parameters were monitored for 270 min postdelivery. It was found that 15 sec after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 9.3+/-8.0 microg x mL(-1) The volume of distribution was 1657+/-321 mL x kg(-1) after 1 2.4+/-1 6.6 min. The extent of tolazoline absorption was 319+/-38 microg x min(-1) mL(-1). The total body clearance was 10.9 +/-4.8 mL x min(-1) x Kg(-1) and the elimination half-life was 156+/-81 min. Endobronchial tolazoline produced an initial short-lived decrease in the mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endobronchial tolazoline a significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. We conclude that an endobronchial bolus dose of tolazoline is effectively absorbed, produces measurable pharmacological effects, and may be beneficial in the therapy of persistent pulmonary hypertension of the newborn.


Subject(s)
Tolazoline/administration & dosage , Tolazoline/pharmacokinetics , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacokinetics , Absorption , Animals , Area Under Curve , Disease Models, Animal , Dogs , Female , Heart Rate/drug effects , Hemodynamics/drug effects , Instillation, Drug , Intubation, Intratracheal , Male , Respiratory System/drug effects , Sensitivity and Specificity , Tolazoline/adverse effects , Vasodilator Agents/adverse effects
17.
Angiology ; 50(3): 233-7, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10088803

ABSTRACT

The authors present two patients with acute arterial vasospasm of the lower extremities causing marked ischemia. One patient had a history of Raynaud's disease, the second had been taking Cafergot for migraine headaches. Both patients's were given a test dose of intra-arterial tolazoline (50 mg). The patient with Raynaud's disease demonstrated marked improvement diffusely and was successfully treated with overnight infusion of papaverine. The second patient, taking Cafergot, demonstrated no angiographic response to tolazoline. It was speculated that the arteries of this patient were thrombosed. The patient was successfully treated with urokinase and remained free of pain at the 15-month follow-up.


Subject(s)
Ischemia/drug therapy , Leg/blood supply , Peripheral Vascular Diseases/drug therapy , Tolazoline/therapeutic use , Vasodilator Agents/therapeutic use , Adult , Caffeine/therapeutic use , Central Nervous System Stimulants/therapeutic use , Drug Combinations , Ergotamine/therapeutic use , Female , Follow-Up Studies , Humans , Infusions, Intra-Arterial , Middle Aged , Migraine Disorders/complications , Migraine Disorders/drug therapy , Papaverine/administration & dosage , Papaverine/therapeutic use , Plasminogen Activators/administration & dosage , Plasminogen Activators/therapeutic use , Raynaud Disease/complications , Thrombosis/complications , Thrombosis/drug therapy , Tolazoline/administration & dosage , Urokinase-Type Plasminogen Activator/administration & dosage , Urokinase-Type Plasminogen Activator/therapeutic use , Vasoconstrictor Agents/therapeutic use , Vasodilator Agents/administration & dosage
18.
Rev. argent. coloproctología ; 9(1): 59-63, mar. 1998. graf
Article in Spanish | LILACS | ID: lil-265667

ABSTRACT

El déficit circulatorio de este cuadro se ubica en la microcirculación intestinal por fallo de bomba, shock o uso de digital. Dolor abdominal repentino, distensión, enterorragia y los antecedentes llevan a la sospecha clínica y al diagnóstico. El tratamiento es en principio médico, con el esquema de Boley (Tolazolina y Papaverina), controlado por arteriografía; si no cede, el intestino necrótico debe ser removido quirúrgicamente. Material y Método: Se consideran 22 casos. Todos consultaron por dolor abdominal repentino, distensión y enterorragia. Sólo 3 carecían de antecedentes, los 19 restantes provenían de UTI, U.C., o tenían tratamiento con digital. Se utilizó el análisis univariable de variables cualitativas. Resultados: Se operaron 18 (81,8 por ciento), falleciendo sin operar 4 (18 por ciento). La mortalidad global fue de 15 (68,1 por ciento). Siete (31,8 por ciento) tuvieron buena evolución, ellos presentaron sólo lesiones de intestino delgado.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Angiography/statistics & numerical data , Intestines/pathology , Ischemia/diagnosis , Ischemia/mortality , Ischemia/surgery , Ischemia/therapy , Mesenteric Arteries , Splanchnic Circulation , Abdominal Pain/diagnosis , Multivariate Analysis , Mesenteric Vascular Occlusion , Papaverine/administration & dosage , Papaverine/therapeutic use , Tolazoline/administration & dosage , Tolazoline/therapeutic use
19.
Rev. argent. coloproctología ; 9(1): 59-63, mar. 1998. graf
Article in Spanish | BINACIS | ID: bin-12251

ABSTRACT

El déficit circulatorio de este cuadro se ubica en la microcirculación intestinal por fallo de bomba, shock o uso de digital. Dolor abdominal repentino, distensión, enterorragia y los antecedentes llevan a la sospecha clínica y al diagnóstico. El tratamiento es en principio médico, con el esquema de Boley (Tolazolina y Papaverina), controlado por arteriografía; si no cede, el intestino necrótico debe ser removido quirúrgicamente. Material y Método: Se consideran 22 casos. Todos consultaron por dolor abdominal repentino, distensión y enterorragia. Sólo 3 carecían de antecedentes, los 19 restantes provenían de UTI, U.C., o tenían tratamiento con digital. Se utilizó el análisis univariable de variables cualitativas. Resultados: Se operaron 18 (81,8 por ciento), falleciendo sin operar 4 (18 por ciento). La mortalidad global fue de 15 (68,1 por ciento). Siete (31,8 por ciento) tuvieron buena evolución, ellos presentaron sólo lesiones de intestino delgado. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Splanchnic Circulation , Intestines/pathology , Mesenteric Arteries , Ischemia/diagnosis , Ischemia/surgery , Ischemia/therapy , Ischemia/mortality , Angiography/statistics & numerical data , Mesenteric Vascular Occlusion , Tolazoline/administration & dosage , Tolazoline/therapeutic use , Abdominal Pain/diagnosis , Papaverine/administration & dosage , Papaverine/therapeutic use , Multivariate Analysis
20.
J Am Vet Med Assoc ; 212(1): 90-2, 1998 Jan 01.
Article in English | MEDLINE | ID: mdl-9426787

ABSTRACT

OBJECTIVE: To test effectiveness of IV administration of tolazoline hydrochloride in reversing xylazine hydrochloride-induced sedation in calves. DESIGN: Prospective study. ANIMALS: 12 female and 12 male Friesian-cross calves from 5 to 7 months old. PROCEDURE: Calves were assigned to 1 of 4 treatment groups. Calves were given xylazine (0.3 mg/kg [0.14 mg/lb] of body weight, IM). Twenty minutes later, calves were treated with saline (0.9% NaCl) solution (1 ml/50 kg [1 ml/110 lb], IV) or tolazoline (1, 2, or 4 mg/kg [0.45, 0.9, or 1.8 mg/lb], IV). Behavioral and physiologic measurements included elapsed time from xylazine administration to recumbency, arousal and standing times after reversal drug administration, heart rate, and respiratory rate. RESULTS: Mean (+/- SD) recumbency time for all calves was 5.4 +/- 1.8 minutes. Compared with administration of saline solution, all 3 doses of tolazoline significantly decreased arousal and standing times. Mean arousal time for calves receiving saline solution was 27.8 +/- 11.5 minutes. Administration of tolazoline at 1, 2, and 4 mg/kg resulted in mean arousal times of 4.7 +/- 3.8, 0.9 +/- 0.5, and 0.7 +/- 0.3 minutes, respectively. Mean standing time for calves receiving saline solution was 38.8 +/- 2.8 minutes. Administration of tolazoline at 1, 2, and 4 mg/kg resulted in mean standing times of 14.0 +/- 11.0, 3.0 +/- 1.2, and 2.4 +/- 1.1 minutes, respectively. CLINICAL IMPLICATIONS: For routine use, tolazoline doses of 1 to 2 mg/kg should suffice. In cattle, IV administration of tolazoline reverses pharmacologic effects of xylazine, thereby hastening recovery from xylazine-induced sedation.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Cattle/physiology , Hypnotics and Sedatives/antagonists & inhibitors , Tolazoline/pharmacology , Xylazine/antagonists & inhibitors , Adrenergic alpha-Antagonists/administration & dosage , Animals , Arousal/drug effects , Female , Hypnotics and Sedatives/administration & dosage , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Male , Time Factors , Tolazoline/administration & dosage , Xylazine/administration & dosage
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