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1. |
Tissue‐chamber modeling systems ‐applications in veterinary medicine |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 349-368
C. R. CLARKE,
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ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00686.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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2. |
Pharmacokinetic disposition of an immediate‐release aminophylline and a sustained‐release theophylline formulation in the horse |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 369-377
T. E. GOETZ,
I.J. MUNSIFF,
B. C. McKIERNAN,
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摘要:
The pharmacokinetic disposition of theophylline was determined by high‐performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate‐release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained‐release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (Λz), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 ± 0.01 h‐1, 0.80 ± 0.06 l/kg, and 0.06 ± 0.01 l/kg/h (mean ± SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P<0.05) for the immediate‐release aminophylline (13.8 ± 2.8 h) and sustained‐release theophylline (18.2 ± 2.3 h) formulation. Immediate‐release aminophylline tablets quickly achieved peak theophylline plasma concentrations of 11.51 ± 1.4 μg/ml at 1–6 ± 0.6 h while the sustained‐release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 ± 1.3 μg/ml at 7.3 ± 1.0 h. Absolute bioavailability was 87% for the immediate‐release and 97% for the sustained‐release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained‐release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough–peak theophylline plasma
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00687.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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3. |
Cardiovascular effects of detomidine, a new α2‐adrenoceptor agonist, in the conscious pony |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 378-388
R. D. SARAZAN,
W. A. STARKE,
G. F. KRAUSE,
H. E. GARNER,
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摘要:
The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post‐injection. The magnitude of the pressure change did not increase with detomidine doses greater than 20 μg/kg. There was a dose‐dependent effect on the duration of the hypertension. Bradycardia and A‐V blockade of similar magnitude followed the hypertension at all drug doses. Both drugs caused a negative inotropic effect on the heart at all doses. Minute work, a mechanical index of myocardial O2demand, and coronary flow decreased to a similar extent following all drug treatments. With the exception of a greater hypertensive response, detomidine at the dosages studied, produced cardiovascular effects that were very similar to those of the recommended dosage of xy
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00688.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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4. |
Cardiopulmonary effects of ephedrine in halothane‐anesthetized horses |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 389-396
J. L. GRANDY,
D. S. HODGSON,
C. I. DUNLOP,
P. L. CHAPMAN,
R. B. HEATH,
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摘要:
The cardiopulmonary effects of intravenous (i.v.) administration of the sympathomimetic drug ephedrine during two different levels of halothane anesthesia [end‐tidal concentration of 1.37% (light anesthesia) and 2.1% (deep anesthesia)] were studied in eight horses. Anesthesia was induced and maintained using only halothane in O2. Ventilation was controlled to maintain a Paco2of 38–42 mmHg. Following instrumentation and stabilization of the horse at the halothane concentration being studied, baseline measurements of cardiac output (®), arterial blood pressure (AP), pulmonary artery pressure, heart rate,Po2,Paco2and pH were made. Ephedrine was then administered (0.06 mg/kg i.v.) and these measurements repeated at 10, 20, 30, 45 and 60 min after injection. At both doses of halothane there was a significant (P<0.05) increase in ®, stroke volume (SV), and systolicAPfollowing ephedrine administration. In addition, at 2.1% halothane, ephedrine administration resulted in a significant (P<0.05) increase in meanAPandPao2and a decrease in total peripheral resistance. The increase in systolicAP, ®, andSVwas significantly (P<0.05) greater at 2.1% halothane than at 1.37% halothane. Ephedrine administration to horses during both light and deep halothane anesthesia results in an increase inAPthat is due to an increase in
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00689.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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5. |
Opioid modulation of tonic luteinizing hormone release in ovariectomized dairy cows |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 397-403
A. S. NANDA,
W. R. WARD,
H. DOBSON,
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摘要:
A possible role of endogenous opioid peptides (EOP) in regulating the release of luteinizing hormone (LH) in the absence of ovarian influence was investigated. Experiments were conducted on three lactating Holstein–Friesian dairy cows, 20–27 days after ovariectomy. The cows were bled before and after a single intravenous (i.v.) injection of either 250 mg of naloxone (EOP antagonist) or 300 mg of morphine (EOP agonist) or a combination of the two in Experiments 1, 2 and 3, respectively. The mean and basal LH concentrations and the LH pulse frequency and amplitude were compared before and after each treatment in each cow. Naloxone induced an immediate rise in LH concentration by 60–300% above the preceding baseline values. This rise lasted for 15–30 min in each cow, after which the normal rhythmic LH release continued. One cow (A) suffered discomfort and respiratory distress 15–25 min after naloxone administration and the mean and basal LH concentration dropped significantly. Morphine significantly reduced the mean LH concentration by decreasing the number and amplitude of LH pulses and the basal LH values in two cows, although the decrease in one was not significant. The mean LH concentration in each cow remained unaffected by the combined treatment of morphine and naloxone. In conclusion, the elevation of LH concentration by naloxone, the suppression of LH release by morphine and the reversal by morphine and naloxone of each other's effects suggest that EOP could be involved in the control of LH release in cows in the absence of ovarian
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00690.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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6. |
Effect of calcium‐channel blockers and salbutamol on the isolated mare uterus — interaction with the calcium agonist Bay K 8644 |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 404-410
G. CORUZZI,
E. POLI,
G. BERTACCINI,
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摘要:
The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium‐channel blockers and salbutamol inhibited the spontaneous, KC1‐ and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10‐8‐10‐6mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2value = 8.54 ± 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium‐channel blockers are potent inhibitors of mare uterine motilityin vitroand emphasize the importance of Ca2+‐related mechanisms in the control of uterine smooth‐muscle contractility. Moreover, the validity of Bay K 8644 as a tool to distinguish classes of calcium‐channel antago
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00691.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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7. |
Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra) |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 411-420
F. D. GALEY,
V. R. BEASLEY,
D. J. SCHAEFFER,
L. E. DAVIS,
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摘要:
Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n= 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37°C. Six‐point Epi concentration‐response (C–R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each vessel using one of two concentrations of one of the three test drugs. Each drug and concentration combination was tested on a total of three arteries and three veins. Prazosin produced a concentration‐dependent shift of the Epi C–R curve to the right but the curve maintained the same maximum height and slope, which is consistent with competitive α1adrenergic blockade. Isoxsuprine exhibited similar behavior, although the precise mechanism of action for isoxsuprine is unknown. Conversely, nifedipine did not shift the curve but did depress maximum contraction, suggesting a non‐competitive interaction consistent with its mechanism of calcium‐c
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00692.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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8. |
The disposition of albendazole in sheep |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 421-429
D. R. HENNESSY,
J. W. STEEL,
E. LACEY,
G. K. EAGLESON,
R. K. PRICHARD,
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摘要:
Albendazole (ABZ) was administered intraruminally at 4.75 mg/kg to sheep fitted with a permanent bile‐duct cannula to determine if its metabolites might contribute to its flukicidal action. ABZ metabolism was consistent with first‐pass clearance by the liver, resulting in ABZ sulphoxide (ABZ‐SO) and ABZ sulphone (ABZ‐SO2) being present in plasma at maximum concentrations (meanCmax± SD) of 2.0 ± 0.2 μg/ml and 0.4 ± 0.1 μg/ml after 8 ± 3 h and 24 ± 5 h, respectively. ABZ‐SO, but more particularly ABZ‐SO2, appeared to bind to plasma proteins but their clearance rates from plasma were similar. Biliary ABZ metabolites were mainly unconjugated ABZ‐SO and 2OH‐ABZ‐SO (8.0% dose) or conjugated glucuronide and sulphate esters (6.3% dose) mainly of 2OH‐ABZ‐SO and 2OH‐ABZ‐SO2. The concentration of the major biliary metabolite, unconjugated ABZ‐SO, followed a similar time profile to that of ABZ‐SO in plasma except thatCmaxwas much higher (6.2 ± 2.2 μg/ml). Intraruminal administration of ABZ reduced bile flow rate by 30% which may be attributable to an inhibitory effect of ABZ on microtubule formation in hepatic secretory cells. It is suggested that ABZ is sequestered in the liver. This is unlikely to contribute to its flukicidal action, which is probably attributable to ingestion of A
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00693.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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9. |
Central and peripheral β‐adrenergic influences on reticulo‐rumen and upper‐gut myoelectrical activity in sheep |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 430-437
P. BRIKAS,
L. BUÉNO,
J. FIORAMONTI,
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摘要:
The effects of intravenous (i.v.) and intracerebroventricular (i.e.v.) administration of β‐adrenoceptor agonists were evaluated on the reticulo‐rumen and upper‐gut myoelectrical activity in six ewes chronically fitted with intraparietal electrodes and a cannula in a lateral ventricle of the brain. Intravenous infusion of the β1agonist dobutamine (30 μg/kg/min for 15 min) reduced the frequency of reticulo‐ruminal and abomasal contractions and stimulated duodeno‐jejunal motility, inducing a Phase III on the jejunum. These effects were reproduced by i.c.v. dobutamine at a dose of 10 μg/kg. Intravenous infusion of the β2agonist ritodrine (15 μg/kg/min for 15 min) selectively inhibited antral and duodenal motility. Ritodrine i.c.v. (15 μg/kg) did not affect forestomach or gastrointestinal motility. The mixed β1, β2agonist isoprenaline infused i.v. (0.6 μg/kg/min for 15 min) reproduced the effects of i.v. dobutamine, except at the antro‐duodenal level which was strongly inhibited. The effects of i.v. dobutamine were antagonized by i.v. or i.c.v. acebutolol, a specific β1antagonist. The effects of i.v. ritodrine were blocked by i.v. but not i.c.v. administration of propranolol, a mixed β1, β2antagonist. These data indicate that the stimulation of central β1adrenoceptors inhibits forestomach and antral motility and stimulates duodeno‐jejunal motility. Stimulation of peripheral β2adrenoceptors selectively inhib
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00694.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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10. |
Absorption of two trimethoprim/sulphonamide combinations from the uterus of pony mares |
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Journal of Veterinary Pharmacology and Therapeutics,
Volume 12,
Issue 4,
1989,
Page 438-443
E. H. BOYD,
W. E. ALLEN,
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摘要:
Plasma drug concentrations were measured after two commercially available potentiated sulphonamides, trimethoprim and sulfadoxine and trimethoprim and sulphadiazine, were infused daily for 2 and 3 days, respectively, into the uteri of pony mares which had been mated before ovulation. Intravenous administration of trimethoprim and sulfadoxine allowed uterine absorption of trimethoprim (23–43%) and sulfadoxine (29–34%) to be calculated. After intrauterine administration trimethoprim and sulphadiazine were detected in the milk of a lactating mare. In order to maintain plasma concentrations likely to be required for clinical efficacy of both drugs they should be administered every 12 h. However, infusions of both preparations caused endometrial inflammation as assessed by cytological and histological examination and this may have been responsible for the low pregnancy r
ISSN:0140-7783
DOI:10.1111/j.1365-2885.1989.tb00695.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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